1
|
Burtscher J, Gatterer H, Niederseer D, Vonbank K, Burtscher M. Flying to high-altitude destinations. Minerva Med 2025; 116:43-61. [PMID: 39101381 DOI: 10.23736/s0026-4806.24.09286-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 08/06/2024]
Abstract
Every year millions of people fly to high-altitude destinations. They thereby expose themselves to specific high-altitude conditions. The hypoxic environment (low ambient oxygen availability) constitutes a major factor affecting health and well-being at high altitude. While the oxygen availability is already moderately reduced inside the aircraft cabin, this reduction becomes aggravated when leaving the plane at high-altitude destinations. Especially if not pre-acclimatized, the risk of suffering from high-altitude illnesses, e.g., acute mountain sickness, high-altitude cerebral or pulmonary edema, increases with the level of altitude. In addition, diminished oxygen availability impairs exercise tolerance, which not only limits physical activity at high altitude but may also provoke symptomatic exacerbation of pre-existing diseases. Moreover, the cold and dry ambient air and increased levels of solar radiation may contribute to adverse health effects at higher altitude. Thus, medical pre-examination and pre-flight advice, and proper preparation (pre-acclimatization, exercise training, and potentially adaptation of pharmacological regimes) are of utmost importance to reduce negative health impacts and frustrating travel experiences.
Collapse
Affiliation(s)
- Johannes Burtscher
- Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland
| | - Hannes Gatterer
- Institute of Mountain Emergency Medicine, Eurac Research, Bolzano, Italy
- Institute for Sports Medicine, Alpine Medicine and Health Tourism (ISAG), UMIT TIROL-Private University for Health Sciences and Health Technology, Hall in Tirol, Austria
| | - David Niederseer
- Hochgebirgsklink Davos, Medicine Campus Davos, Davos, Switzerland
- Christine Kühne - Center for Allergy Research and Education, Medicine Campus Davos, Davos, Switzerland
- Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | | | - Martin Burtscher
- Department Sport Science, University of Innsbruck, Innsbruck, Austria -
| |
Collapse
|
2
|
Bakshi J, Mishra KP. Sodium butyrate prevents lipopolysaccharide induced inflammation and restores the expression of tight junction protein in human epithelial Caco-2 cells. Cell Immunol 2025; 408:104912. [PMID: 39729961 DOI: 10.1016/j.cellimm.2024.104912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 09/17/2024] [Revised: 12/13/2024] [Accepted: 12/20/2024] [Indexed: 12/29/2024]
Abstract
The gastrointestinal (GI) tract is susceptible to damage under high altitude hypoxic conditions, leading to gastrointestinal discomfort and intestinal barrier injury. Sodium butyrate, a short-chain fatty acid present as a metabolite in the gut, has emerged as a promising therapeutic agent due to its ability to act as an immunomodulatory agent and restore intestinal barrier integrity. This study aimed to explore the mechanism by which sodium butyrate exhibits anti inflammatory effect on intestinal epithelial cells. In vitro, Caco-2 epithelial cells and RAW 264.7 macrophages were used to investigate the protective role of sodium butyrate on Lipopolysaccharide (LPS) induced inflammation. Cell viability assays demonstrated that 1 mM (110.86 μg/mL) of sodium butyrate did not exhibit cytotoxicity on cells in vitro. Treatment with sodium butyrate suppressed reactive oxygen species levels and TNF-α production in LPS-stimulated macrophages, indicating its efficacy in mitigating inflammatory responses. Western blot analysis revealed that sodium butyrate attenuated the expression of iNOS in RAW 264.7 macrophage cells. Moreover, sodium butyrate also reversed the LPS induced over expression of HIF-1α, NLRP3, IL-1β as well as NF-kB in Caco-2 epithelial cells and also had a suppressive effect on IL-8 secretion after LPS stimulation. Immunocytochemistry demonstrated that sodium butyrate enhanced tight junction protein occludin expression in Caco-2 cells while also restoring the decreased permeability of the Caco-2 monolayer due to LPS. These results indicate that sodium butyrate may influence immune responses by suppressing inflammatory mediators and improving the integrity of the epithelial barrier. Understanding the intricate interactions between gut metabolites and host immune responses may help in the development of innovative therapeutic strategies to alleviate intestinal inflammation in high altitude environments.
Collapse
Affiliation(s)
- Jyotsana Bakshi
- Defence Institute of Physiology and Allied Sciences, Delhi 110054, India
| | - K P Mishra
- Defence Institute of Physiology and Allied Sciences, Delhi 110054, India.
| |
Collapse
|
3
|
Xie Y, Sun Y, Shao Y, Tian J, Fu Y, Yang D, Yang Y, Cao K, Zhang Y, Wang H, Wang G, Wang N. Impact of Acute Short-Term Hypobaric Hypoxia on Anterior Chamber Geometry. J Glaucoma 2025; 34:136-143. [PMID: 39311802 PMCID: PMC11771345 DOI: 10.1097/ijg.0000000000002498] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 01/20/2024] [Accepted: 08/31/2024] [Indexed: 01/28/2025]
Abstract
PRCIS Hypobaric hypoxia, the major environmental factor at high altitudes, has been observed to induce pupil miosis and widening of the anterior chamber angle. This environment may be safe for individuals with narrow angle and deserves further study. PURPOSE This study aimed to quantify anterior chamber biometric parameters before and after acute short-term, effortless exposure to hypobaric hypoxia (HH) in healthy lowlanders using swept-source anterior segment optical coherence tomography (SS AS-OCT). METHODS This prospective study included 25 healthy young lowlanders (50 eyes) who underwent SS AS-OCT measurements and intraocular pressure (IOP) assessments under baseline sea-level conditions (T1). They were then passively exposed to simulated 4000 m above sea level for 3 hours and underwent acute mountain sickness (AMS) symptoms evaluation and IOP measurement after 2 hours exposure to HH (T2). Repeat SS AS-OCT measurements and IOP assessments were taken within 15 minutes after leaving the hypobaric chamber (T3). Anterior segment parameters including anterior chamber depth (ACD), lens vault (LV), angle opening distance (AOD500), trabecular-iris space area (TISA500), angle recess area (ARA500) at 500 μm from the scleral spur, iris curvature (IC), iris volume (IV), pupil diameter (PD), and central corneal thickness (CCT) were obtained through SS AS-OCT. These repeated measurements were compared using linear mixed model analysis. RESULTS In comparison to the sea level, both IOP (16.4±3.4 vs. 14.9±2.4 mm Hg, P =0.029) and PD (5.36±0.77 vs. 4.78±0.89 mm, P =0.001) significantly decreased after exposure to HH. Significant post-HH changes [mean difference (95% CI)] were observed in AOD500 [0.129 (0.006, 0.252), P =0.04], TISA500 [0.059 (0.008, 0.11), P =0.025], ARA500 [0.074 (0.008, 0.141), P =0.029], IV [1.623 (0.092, 3.154), P =0.038], and IC [-0.073 (-0.146, 0.001), P =0.047], whereas CCT, ACD, and LV remained stable. After adjusting for age, post-HH variations in AOD500 (Beta=0.553, 95% CI: 0.001, 1.105, P =0.048) and TISA500 (Beta=0.256, 95% CI: 0.02, 0.492, P =0.034) were associated with decreased IC but were not related to lowered arterial oxygen pressure or IV increase per millimeter of pupil miosis (IV/PD). These differences in anterior segment parameters were neither correlated with differences in IOP nor AMS. CONCLUSIONS After short-term, effortless exposure to hypobaric hypoxia, pupil miosis occurred with widening of the anterior chamber angle and decreased IC. These changes in anterior chamber angle parameters were associated with decreased IC but did not correlate with the post-hypobaric variations in IV/PD, IOP, or AMS.
Collapse
Affiliation(s)
- Yuan Xie
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory
| | - Yunxiao Sun
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory
| | - Yaqi Shao
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory
- Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University
| | - Jiaxing Tian
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory
| | - Yingdi Fu
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory
- Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University
| | - Diya Yang
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory
| | - Yiquan Yang
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory
| | - Kai Cao
- Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University
| | - Ye Zhang
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory
| | - Huaizhou Wang
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory
| | - Guozhong Wang
- Department of Hyperbaric and Hypobaric Chamber, Civil Aviation General Hospital, Beijing, China
| | - Ningli Wang
- Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory
- Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University
| |
Collapse
|
4
|
Peng W, Ma H, Zhao R, Xu S, Lv M, Jing B, Hu Z. Role of intermittent hypoxic training combined with methazolamide in the prevention of high-altitude cerebral edema in rats. Sci Rep 2024; 14:30252. [PMID: 39632926 PMCID: PMC11618614 DOI: 10.1038/s41598-024-81226-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 07/30/2024] [Accepted: 11/25/2024] [Indexed: 12/07/2024] Open
Abstract
Although intermittent hypoxia training (IHT) and methazolamide (MTZ) alone can prevent high-altitude cerebral edema (HACE) to varying degrees, their efficacy and dispersion remain limited. However, only a handful of trials have explored the effectiveness of the IHT and MTZ combination in preventing HACE. Rats were first exposed to hypobaric hypoxia (5000 m, 54.02 kPa, 10.8% fraction of inspired oxygen (FiO2)) with simultaneous exhaustive exercise (EE) for different durations to determine the ideal condition for establishing a rat model of HACE. Rats receiving various courses of IHT were subjected to this condition, and changes in behaviour, brain water content (BWC), pathology and brain protein expression were evaluated. Meanwhile, rats received different doses of MTZ before and during hypoxia exposure with simultaneous EE. Finally, rats receiving the IHT and MTZ combination were then exposed to hypoxia with simultaneous EE. Systemic inflammation and mild cerebral edema developed in rats after 6 h of hypobaric hypoxia with simultaneous EE. Rats showed severe impairment of spatial and memory functions after 2 days of hypobaric hypoxia with simultaneous EE, and the pathology of their brain showed significant dilated perivascular spaces, cell swelling, vacuolar degeneration and reduced neuron count. BWC, serum inflammatory factors and expression of vascular endothelial growth factor (VEGF) and aquaporin 4 (AQP4) proteins in the hippocampus increased significantly. Both IHT and MTZ differentially counteracted hypobaric hypoxia-induced spatial and memory function impairments and increased BWC, pathological changes and expression of AQP4 and VEGF proteins in the hippocampus. Among these, the long-course IHT (BID, 14 d) combined with MTZ (200 mg/kg/d) showed the most significant improvement, restoring the rats' indices to normal levels. Continuous hypobaric hypoxia with simultaneous EE for 2 days resulted in significant HACE in rats, which may be used to establish a rat model of HACE. Both IHT and MTZ alleviated HACE in rats to varying degrees, among which long-course IHT (BID, 14 d) combined with MTZ (200 mg/kg/d) effectively prevented HACE in rats.
Collapse
Affiliation(s)
- Weicheng Peng
- Department of Neurosurgery, Neuromedicine Center, Beijing Shijitan Hospital, Capital Medical University, No. 10, Tieyi Road, Yangfangdian, Haidian District, Beijing, 100038, China
| | - Haiyang Ma
- Department of Neurosurgery, Neuromedicine Center, Beijing Shijitan Hospital, Capital Medical University, No. 10, Tieyi Road, Yangfangdian, Haidian District, Beijing, 100038, China
| | - Rui Zhao
- Department of Neurosurgery, Neuromedicine Center, Beijing Shijitan Hospital, Capital Medical University, No. 10, Tieyi Road, Yangfangdian, Haidian District, Beijing, 100038, China
| | - Sheng Xu
- Department of Neurosurgery, Neuromedicine Center, Beijing Shijitan Hospital, Capital Medical University, No. 10, Tieyi Road, Yangfangdian, Haidian District, Beijing, 100038, China
| | - Meng Lv
- Department of Neurosurgery, Neuromedicine Center, Beijing Shijitan Hospital, Capital Medical University, No. 10, Tieyi Road, Yangfangdian, Haidian District, Beijing, 100038, China
| | - Bei Jing
- Department of Neurosurgery, Neuromedicine Center, Beijing Shijitan Hospital, Capital Medical University, No. 10, Tieyi Road, Yangfangdian, Haidian District, Beijing, 100038, China
| | - Zhiqiang Hu
- Department of Neurosurgery, Neuromedicine Center, Beijing Shijitan Hospital, Capital Medical University, No. 10, Tieyi Road, Yangfangdian, Haidian District, Beijing, 100038, China.
| |
Collapse
|
5
|
Yan C, Ma J, Tian D, Yan T, Zhang C, Zhang F, Zhao Y, Fu S, Zhang Q, Xia M, Li Y, Sun Y. Evaluation of pulmonary artery pressure, blood indices, and myocardial microcirculation in rats returning from high altitude to moderate altitude. Eur Radiol Exp 2024; 8:131. [PMID: 39565546 PMCID: PMC11579275 DOI: 10.1186/s41747-024-00514-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 11/17/2023] [Accepted: 09/09/2024] [Indexed: 11/21/2024] Open
Abstract
BACKGROUND To investigate changes in pulmonary artery pressure (PAP), blood indices, and myocardial microcirculation in rats returning from high altitude (HA) to moderate altitude (MA). METHODS Forty 4-week-old male Sprague-Dawley rats were randomly divided into four groups with ten rats in each group. One group was transported to the MA area (MA-group), and the other three groups were transported to HA (HA-group-A, HA-group-B, and HA-group-C). After 28 weeks of age, the rats from the HA area were transported to the MA area for 0 days, 10 days, and 20 days, respectively. PAP, routine blood tests, and computed tomography myocardial perfusion indices were measured. RESULTS Compared with the MA-group, the body weight of HA-groups decreased (p < 0.05), and PAP in HA-group-A and HA-group-B increased (p < 0.05). In the HA groups, PAP initially increased and then decreased. Compared with the MA-group, red blood cells (RBC), hemoglobin (HGB), and hematocrit (HCT) of rats in HA-group-A increased (p < 0.05). Compared with the HA-group-A, RBC, HGB, and HCT of HA-group-B gradually decreased (p < 0.05) while MCV decreased (p < 0.05), and PLT of HA-group-C increased (p < 0.05). Compared with the MA group, blood flow (BF) and blood volume (BV) of the HA-group-A decreased (p < 0.05). Compared with the HA-group-A, TTP increased first and then decreased (p < 0.05), and BF and BV increased gradually (p < 0.05). Pathological results showed that myocardial fiber arrangement was disordered, and cell space widened in the HA group. CONCLUSION PAP, blood parameters, and myocardial microcirculation in rats returning from high to MA exhibited significant changes. RELEVANCE STATEMENT This study provides an experimental basis for understanding the physiological and pathological mechanisms during the process of deacclimatization to HA and offers new insights for the prevention and treatment of deacclimatization to HA syndrome. KEY POINTS Forty rats were raised in a real plateau environment. Myocardial microcirculation was detected by CT myocardial perfusion imaging. The PAP of the unacclimated rats increased first and then decreased. The myocardial microcirculation of the deacclimated rats showed hyperperfusion changes.
Collapse
Affiliation(s)
- Chunlong Yan
- Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
- Department of Radiology, Jining No.1 People's Hospital, Jining, China
- Department of Radiology, Qinghai Provincial People's Hospital, Xining, China
| | - Jinfeng Ma
- Department of Hematology, Jining No.1 People's Hospital, Jining, China
| | - Dengfeng Tian
- Department of Radiology, Qinghai Provincial People's Hospital, Xining, China
| | | | - Chenhong Zhang
- Department of Radiology, Qinghai Provincial People's Hospital, Xining, China
| | - Fengjuan Zhang
- Department of Radiology, Qinghai Provincial People's Hospital, Xining, China
- Graduate School of Qinghai University, Xining, China
| | - Yuchun Zhao
- Department of Radiology, Qinghai Provincial People's Hospital, Xining, China
- Graduate School of Qinghai University, Xining, China
| | - Shihan Fu
- Department of Radiology, Qinghai Provincial People's Hospital, Xining, China
- Graduate School of Qinghai University, Xining, China
| | - Qiang Zhang
- Department of Neurosurgery, Qinghai Provincial People's Hospital, Xining, China
| | - Mengxue Xia
- Department of Radiology, Qinghai Provincial People's Hospital, Xining, China
- Graduate School of Qinghai University, Xining, China
| | - Yue Li
- Department of Radiology, Qinghai Provincial People's Hospital, Xining, China
- Graduate School of Qinghai University, Xining, China
| | - Yanqiu Sun
- Department of Radiology, Qinghai Provincial People's Hospital, Xining, China.
| |
Collapse
|
6
|
Dhakal A, Si J, Sapkota S, Pauciullo A, Han J, Gorkhali NA, Zhao X, Zhang Y. Whole-genome sequencing reveals genetic structure and adaptive genes in Nepalese buffalo breeds. BMC Genomics 2024; 25:1082. [PMID: 39543523 PMCID: PMC11566569 DOI: 10.1186/s12864-024-10993-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 04/24/2024] [Accepted: 11/05/2024] [Indexed: 11/17/2024] Open
Abstract
BACKGROUND Indigenous buffaloes, as the important livestock species contributing to economy of the country, are the lifeline of livelihood in Nepal. They are distributed across diverse geographical regions of the country and have adapted to various feeding, breeding, and management conditions. The larger group of these native buffalo breeds are present in narrow and stiff hilly terrains. Their dispersal indicates a possible environmental adaptation mechanism, which is crucial for the conservation of these breeds. RESULTS We utilized whole-genome sequencing (WGS) to investigate the genetic diversity, population structure, and selection signatures of Nepalese indigenous buffaloes. We compared 66 whole-genome sequences with 118 publicly available sequences from six river and five swamp buffalo breeds. Genomic diversity parameters indicated genetic variability level in the Nepalese buffaloes comparable to those of Indian breeds, and population genetic structure revealed distinct geography-mediated genetic differentiation among these breeds. We used locus-specific branch length analysis (LSBL) for genome-wide scan, which revealed a list of potentially selected genes in Lime and Parkote breeds that inhabit the hilly region. A gene ontology (GO) analysis discovered that many GO terms were associated with cardiac function regulation. Furthermore, complementary analyses of local selection signatures, tissue expression profiles, and haplotype differences identified candidate genes, including KCNE1, CSF1R, and PDGFRB, related to the regulation of cardiac and pulmonary functions. CONCLUSIONS This study is a comprehensive WGS-based genetic analysis of the native Nepalese buffalo breeds. Our study suggested that the Nepalese "hilly" buffaloes, especially the Lime and Parkote breeds, have undergone some characteristic genetic changes and evolved increased cardiac and pulmonary function for their adaptation to the steep hilly terrains of the country.
Collapse
Affiliation(s)
- Aashish Dhakal
- State Key Laboratory of Animal Biotech Breeding, National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Jingfang Si
- State Key Laboratory of Animal Biotech Breeding, National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China
| | - Saroj Sapkota
- National Animal Breeding and Genetics Research Centre, Nepal Agricultural Research Council, Lalitpur, Nepal
| | - Alfredo Pauciullo
- Department of Agricultural, Forest and Food Sciences, University of Torino, Grugliasco, 10095, Italy
| | - Jianlin Han
- Yazhouwan National Laboratory, Sanya, 572024, China
| | - Neena Amatya Gorkhali
- National Animal Breeding and Genetics Research Centre, Nepal Agricultural Research Council, Lalitpur, Nepal.
| | - Xingbo Zhao
- State Key Laboratory of Animal Biotech Breeding, National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
| | - Yi Zhang
- State Key Laboratory of Animal Biotech Breeding, National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
| |
Collapse
|
7
|
Berek K, Lindner A, Pauli FD, Bsteh G, Treml B, Ponleitner M, Engler C, Kleinsasser A, Berger T, Wille M, Burtscher M, Deisenhammer F, Hegen H. Neurofilament Light Chain Is Associated With Acute Mountain Sickness. Brain Behav 2024; 14:e70165. [PMID: 39552103 PMCID: PMC11570677 DOI: 10.1002/brb3.70165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 04/18/2024] [Revised: 10/18/2024] [Accepted: 10/31/2024] [Indexed: 11/19/2024] Open
Abstract
BACKGROUND Neurological symptoms are common in acute mountain sickness (AMS); however, the extent of neuroaxonal damage remains unclear. Neurofilament light chain (NfL) is an established blood biomarker for neuroaxonal damage. OBJECTIVE To investigate whether plasma (p) NfL levels increase after simulated altitude exposure, correlate with the occurrence of AMS, and might be mitigated by preacclimatization. METHODS Healthy subjects were exposed to simulated high altitude (4500 m) by the use of a normobaric hypoxic chamber at the University of Innsbruck two times, that is, within Cycle 1 (C1) over 12 h, and within Cycle 2 (C2) for another 12 h but with a random assignment to prior acclimatization or sham acclimatization. Before each cycle (measurement [M] 1 and 3) and after each cycle (M2 and M4), clinical data (arterial oxygen saturation [SaO2], heart rate, and Lake Louise AMS score [LLS]) and plasma samples were collected. pNfL was measured using single-molecule array (Simoa) technique. RESULTS pNfL levels did not significantly change within each study cycle, but increased over the total study period (M1: 4.57 [3.34-6.39], M2: 4.58 [3.74-6.0], M3: 5.64, and M4: 6.53 [4.65-7.92] pg/mL, p < 0.001). Subjects suffering from AMS during the study procedures showed higher pNfL levels at M4 (6.80 [6.19-8.13] vs. 5.75 [4.17-7.35], p = 0.048), a higher total pNfL increase (2.88 [1.21-3.48] vs. 0.91 [0.53-1.48], p = 0.022) compared to subjects without AMS. An effect of preacclimatization on pNfL levels could not be observed. CONCLUSIONS pNfL increases alongside exposure to simulated altitude and is associated with AMS.
Collapse
Affiliation(s)
- Klaus Berek
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Anna Lindner
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Franziska Di Pauli
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| | - Gabriel Bsteh
- Department of Neurology, Medical University of Vienna, Vienna, Austria
- Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria
| | - Benedikt Treml
- Department of Anaesthesiology and Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Markus Ponleitner
- Department of Neurology, Medical University of Vienna, Vienna, Austria
- Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria
| | - Clemens Engler
- Department of Surgery, University Hospital for Cardiac Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Axel Kleinsasser
- Department of Anaesthesiology and Critical Care Medicine, Medical University of Innsbruck, Innsbruck, Austria
| | - Thomas Berger
- Department of Neurology, Medical University of Vienna, Vienna, Austria
- Comprehensive Center for Clinical Neurosciences and Mental Health, Medical University of Vienna, Vienna, Austria
| | - Maria Wille
- Department of Sport Science, University of Innsbruck, Innsbruck, Austria
| | - Martin Burtscher
- Department of Sport Science, University of Innsbruck, Innsbruck, Austria
| | | | - Harald Hegen
- Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
| |
Collapse
|
8
|
Wang X, Fan F, Hou Y, Meng X. Tile: Construction of a specific nanoprobe for scavenging ROS in hypobaric hypoxia induced brain injury of mice. Heliyon 2024; 10:e38958. [PMID: 39640698 PMCID: PMC11620081 DOI: 10.1016/j.heliyon.2024.e38958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 10/30/2023] [Revised: 09/28/2024] [Accepted: 10/03/2024] [Indexed: 12/07/2024] Open
Abstract
The prevention and treatment of hypobaric hypoxia brain injury (HHBI) remains an unprecedented challenge due to the complex oxidative stress response at the damage site. In this study, RuCO phthalocyanine compound (RuPc) and bovine serum albumin (BSA) were self-assembled to obtain RuPc-BSA nanoparticles for HHBI therapy. As a nanoprobe carrying and storing carbon monoxide (CO), RuPc-BSA delivers CO to pathologically damaged areas of the brain. CO specifically attaches itself to the heme functional groups on mitochondria and restricts the source of reactive oxygen species (ROS) generation. RuPc-BSA nanoparticles have been demonstrated in vitro to exhibit amazing stability as well as remarkable scavenging activity on hydroxyl radical, superoxide anion, and hydrogen peroxide. In vivo experiments showed that ROS levels in the brain of HHBI rats pretreated with RuPc-BSA decreased significantly, and neuronal function and oxidative stress levels were alleviated. Western blot and qRT-RCR results indicated that RuPc-BSA restricted the protein levels of Keap1, whereas enhanced the gene and protein levels of Nrf2. This study demonstrated that RuPc-BSA can ameliorate HHBI of mice by scavenging ROS partly via activating Keap1/Nrf2 signaling pathway.
Collapse
Affiliation(s)
- Xiaobo Wang
- Innovative Institute of Chinese Medicine and Pharmacy/Academy for Interdiscipline, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Fuhan Fan
- School of Pharmacy/School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
| | - Ya Hou
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, Sichuan, China
| | - Xianli Meng
- Innovative Institute of Chinese Medicine and Pharmacy/Academy for Interdiscipline, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
- School of Pharmacy/School of Modern Chinese Medicine Industry, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, Sichuan, China
| |
Collapse
|
9
|
Ai C, Bai J, Ye Q, Niu S, Li Y, Li P, Wu H, Wu J, Wang X. Accelerating healing at high altitudes: Oxygen and bFGF delivery through nanoparticle-loaded gel dressings. Biomed Pharmacother 2024; 179:117247. [PMID: 39236477 DOI: 10.1016/j.biopha.2024.117247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 05/06/2024] [Revised: 07/12/2024] [Accepted: 07/30/2024] [Indexed: 09/07/2024] Open
Abstract
High altitude environment is mainly characterized by low oxygen. Due to persistent hypoxia, nonhealing wounds are common in high-altitude areas. Moreover, Basic fibroblast growth factor (bFGF) is a versatile biologically active substance that has crucial impact on wound healing. Given the limited availability of atmospheric oxygen and reduced blood oxygen saturation in high-altitude area, and the challenge that arises from direct oxygen and bFGF delivery to wounds through the traumatized vascular structure, it necessitates an innovative solution for local and permeable delivery of oxygen and bFGF. In this study, we present a strategy that involves revamping traditional gel-based wound dressings through the incorporation of nanoparticles encapsulating oxygen and bFGF, engineered to facilitate the localized delivery of dissolved oxygen and bFGF to wound surfaces. The prospective evaluation of this delivery technique's therapeutic impacts on epithelial, endothelial and fibroblasts cells can be materialized. Further experiment corroborated these effects on a high-altitude wounds' murine model. Given its biocompatibility, efficacy, and utility, we posit that NOB-Gel exhibits remarkable translational potential for managing and hastening the healing process of an array of clinical wounds, more so for wounds inflicted at high altitudes.
Collapse
Affiliation(s)
- Chongyi Ai
- Tianjin Institute of Environmental and Operational Medicine, Tianjin 300050, China
| | - Jin Bai
- Tianjin Institute of Environmental and Operational Medicine, Tianjin 300050, China; School and Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, China
| | - Qingsong Ye
- State Key Laboratory of Pharmaceutical Biotechnology, Chemistry and Biomedicine Innovation Center, Medical School of Nanjing University, Nanjing 210093, China
| | - Siyu Niu
- Tianjin Institute of Environmental and Operational Medicine, Tianjin 300050, China
| | - Yunzhe Li
- Tianjin Institute of Environmental and Operational Medicine, Tianjin 300050, China; School and Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, China
| | - Pan Li
- Tianjin Institute of Environmental and Operational Medicine, Tianjin 300050, China; School and Hospital of Stomatology, Tianjin Medical University, Tianjin 300070, China
| | - Hao Wu
- Tianjin Institute of Environmental and Operational Medicine, Tianjin 300050, China
| | - Jinhui Wu
- State Key Laboratory of Pharmaceutical Biotechnology, Chemistry and Biomedicine Innovation Center, Medical School of Nanjing University, Nanjing 210093, China.
| | - Xinxing Wang
- Tianjin Institute of Environmental and Operational Medicine, Tianjin 300050, China.
| |
Collapse
|
10
|
Ariyeloye S, Kämmerer S, Klapproth E, Wielockx B, El-Armouche A. Intertwined regulators: hypoxia pathway proteins, microRNAs, and phosphodiesterases in the control of steroidogenesis. Pflugers Arch 2024; 476:1383-1398. [PMID: 38355819 PMCID: PMC11310285 DOI: 10.1007/s00424-024-02921-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 12/05/2023] [Revised: 01/25/2024] [Accepted: 02/05/2024] [Indexed: 02/16/2024]
Abstract
Oxygen sensing is of paramount importance for maintaining cellular and systemic homeostasis. In response to diminished oxygen levels, the hypoxia-inducible factors (HIFs) orchestrate various biological processes. These pivotal transcription factors have been identified as key regulators of several biological events. Notably, extensive research from our group and others has demonstrated that HIF1α exerts an inverse regulatory effect on steroidogenesis, leading to the suppression of crucial steroidogenic enzyme expression and a subsequent decrease in steroid levels. These steroid hormones occupy pivotal roles in governing a myriad of physiological processes. Substantial or prolonged fluctuations in steroid levels carry detrimental consequences across multiple organ systems and underlie various pathological conditions, including metabolic and immune disorders. MicroRNAs serve as potent mediators of multifaceted gene regulatory mechanisms, acting as influential epigenetic regulators that modulate a broad spectrum of gene expressions. Concomitantly, phosphodiesterases (PDEs) play a crucial role in governing signal transduction. PDEs meticulously manage intracellular levels of both cAMP and cGMP, along with their respective signaling pathways and downstream targets. Intriguingly, an intricate interplay seems to exist between hypoxia signaling, microRNAs, and PDEs in the regulation of steroidogenesis. This review highlights recent advances in our understanding of the role of microRNAs during hypoxia-driven processes, including steroidogenesis, as well as the possibilities that exist in the application of HIF prolyl hydroxylase (PHD) inhibitors for the modulation of steroidogenesis.
Collapse
Affiliation(s)
- Stephen Ariyeloye
- Institute of Clinical Chemistry and Laboratory Medicine, Medical Faculty, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany
| | - Susanne Kämmerer
- Department of Pharmacology and Toxicology, Medical Faculty, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany
| | - Erik Klapproth
- Department of Pharmacology and Toxicology, Medical Faculty, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany
| | - Ben Wielockx
- Institute of Clinical Chemistry and Laboratory Medicine, Medical Faculty, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
| | - Ali El-Armouche
- Department of Pharmacology and Toxicology, Medical Faculty, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
| |
Collapse
|
11
|
van Veelen MJ, Likar R, Tannheimer M, Bloch KE, Ulrich S, Philadelphy M, Teuchner B, Hochholzer T, Pichler Hefti J, Hefti U, Paal P, Burtscher M. Emergency Care for High-Altitude Trekking and Climbing. High Alt Med Biol 2024. [PMID: 39073038 DOI: 10.1089/ham.2024.0065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 07/30/2024] Open
Abstract
Introduction: High altitude regions are characterized by harsh conditions (environmental, rough terrain, natural hazards, and limited hygiene and health care), which all may contribute to the risk of accidents/emergencies when trekking or climbing. Exposure to hypoxia, cold, wind, and solar radiation are typical features of the high altitude environment. Emergencies in these remote areas place high demands on the diagnostic and treatment skills of doctors and first-aiders. The aim of this review is to give insights on providing the best possible care for victims of emergencies at high altitude. Methods: Authors provide clinical recommendations based on their real-world experience, complemented by appropriate recent studies and internationally reputable guidelines. Results and Discussion: This review covers most of the emergencies/health issues that can occur when trekking or during high altitude climbing, that is, high altitude illnesses and hypothermia, freezing cold injuries, accidents, for example, with severe injuries due to falling, cardiovascular and respiratory illnesses, abdominal, musculoskeletal, eye, dental, and skin issues. We give a summary of current recommendations for emergency care and pain relief in case of these various incidents.
Collapse
Affiliation(s)
- Michiel J van Veelen
- Institute of Mountain Emergency Medicine, Eurac Research, Bolzano, Italy
- Department of Sport Science, University of Innsbruck, Innsbruck, Austria
| | - Rudolf Likar
- Department for Anaesthesiology and Intensive Medicine, Klinikum Klagenfurt am Wörthersee, SFU Vienna, Klagenfurt, Austria
| | - Markus Tannheimer
- Department of Sport and Rehabilitation Medicine, University of Ulm, Ulm, Germany
- Department of General and Visceral Surgery, ADK-Klinik Blaubeuren, Ulm, Germany
| | - Konrad E Bloch
- Department of Pulmonology, University Hospital of Zürich, Zürich, Switzerland
| | - Silvia Ulrich
- Department of Pulmonology, University Hospital of Zürich, Zürich, Switzerland
| | | | - Barbara Teuchner
- Department of Ophthalmology, Medical University of Innsbruck, Innsbruck, Austria
| | | | | | - Urs Hefti
- Swiss Sportclinic, Bern, Switzerland
- Medical Commission, International Climbing and Mountaineering Federation (UIAA), Bern, Switzerland
| | - Peter Paal
- Medical Commission, International Climbing and Mountaineering Federation (UIAA), Bern, Switzerland
- Department of Anaesthesiology and Intensive Care Medicine, St John of God Hospital, Paracelsus Medical University, Salzburg, Austria
- Austrian Society for Alpine- and High-Altitude Medicine, Innsbruck, Austria
| | - Martin Burtscher
- Department of Sport Science, University of Innsbruck, Innsbruck, Austria
- Austrian Society for Alpine- and High-Altitude Medicine, Innsbruck, Austria
| |
Collapse
|
12
|
Gatterer H, Villafuerte FC, Ulrich S, Bhandari SS, Keyes LE, Burtscher M. Altitude illnesses. Nat Rev Dis Primers 2024; 10:43. [PMID: 38902312 DOI: 10.1038/s41572-024-00526-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Accepted: 05/02/2024] [Indexed: 06/22/2024]
Abstract
Millions of people visit high-altitude regions annually and more than 80 million live permanently above 2,500 m. Acute high-altitude exposure can trigger high-altitude illnesses (HAIs), including acute mountain sickness (AMS), high-altitude cerebral oedema (HACE) and high-altitude pulmonary oedema (HAPE). Chronic mountain sickness (CMS) can affect high-altitude resident populations worldwide. The prevalence of acute HAIs varies according to acclimatization status, rate of ascent and individual susceptibility. AMS, characterized by headache, nausea, dizziness and fatigue, is usually benign and self-limiting, and has been linked to hypoxia-induced cerebral blood volume increases, inflammation and related trigeminovascular system activation. Disruption of the blood-brain barrier leads to HACE, characterized by altered mental status and ataxia, and increased pulmonary capillary pressure, and related stress failure induces HAPE, characterized by dyspnoea, cough and exercise intolerance. Both conditions are progressive and life-threatening, requiring immediate medical intervention. Treatment includes supplemental oxygen and descent with appropriate pharmacological therapy. Preventive measures include slow ascent, pre-acclimatization and, in some instances, medications. CMS is characterized by excessive erythrocytosis and related clinical symptoms. In severe CMS, temporary or permanent relocation to low altitude is recommended. Future research should focus on more objective diagnostic tools to enable prompt treatment, improved identification of individual susceptibilities and effective acclimatization and prevention options.
Collapse
Affiliation(s)
- Hannes Gatterer
- Institute of Mountain Emergency Medicine, Eurac Research, Bolzano, Italy.
- Institute for Sports Medicine, Alpine Medicine and Health Tourism (ISAG), UMIT TIROL-Private University for Health Sciences and Health Technology, Hall in Tirol, Austria.
| | - Francisco C Villafuerte
- Laboratorio de Fisiología del Transporte de Oxígeno y Adaptación a la Altura - LID, Departamento de Ciencias Biológicas y Fisiológicas, Facultad de Ciencias e Ingeniería, Universidad Peruana Cayetano Heredia, Lima, Perú
| | - Silvia Ulrich
- Department of Respiratory Medicine, University Hospital Zurich, Zurich, Switzerland
| | - Sanjeeb S Bhandari
- Mountain Medicine Society of Nepal, Kathmandu, Nepal
- Emergency Department, UPMC Western Maryland Health, Cumberland, MD, USA
| | - Linda E Keyes
- Department of Emergency Medicine, University of Colorado, Aurora, CO, USA
| | - Martin Burtscher
- Department of Sport Science, University of Innsbruck, Innsbruck, Austria
| |
Collapse
|
13
|
Guo C, Lan L, Yan Y, Kang M. Effects of acute exposure to hypoxia on sleep structure in healthy adults: A systematic review. Sleep Med Rev 2024; 75:101928. [PMID: 38614049 DOI: 10.1016/j.smrv.2024.101928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 12/15/2023] [Revised: 03/14/2024] [Accepted: 03/21/2024] [Indexed: 04/15/2024]
Abstract
The sleep quality of lowlanders in hypoxic environments has become increasingly important with an increase in highland and alpine activities. This study aimed to identify the effects of acute exposure to hypoxia on the sleep structure of lowlanders and to analyze the changes in sleep indicators at varying levels of hypoxia. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Twenty-three studies were screened and included in the quantitative analysis. The results showed that acute exposure to hypoxia reduced sleep quality in lowlanders. Post-sleep arousal events and the percentage of N1 were significantly increased, whereas total sleep time, sleep efficiency, and the percentage of N3 and rapid eye movement sleep were significantly decreased in hypoxic environments. Acute exposure to hypoxia had the greatest negative impact on wakefulness after sleep onset (WASO). In addition, a larger decrease in sleep efficiency and higher increase in the percentages of N1 and WASO were observed when lowlanders were exposed to higher levels of hypoxia. This study clarifies the quantitative effects of acute hypoxic exposure on sleep in lowlanders based on original studies and explains the sleep disorders faced by lowlanders in hypoxic environments.
Collapse
Affiliation(s)
- Chao Guo
- Department of Architecture, School of Design, Shanghai Jiao Tong University, Shanghai, China
| | - Li Lan
- Department of Architecture, School of Design, Shanghai Jiao Tong University, Shanghai, China.
| | - Yan Yan
- Department of Architecture, School of Design, Shanghai Jiao Tong University, Shanghai, China
| | - Mengyuan Kang
- Department of Architecture, School of Design, Shanghai Jiao Tong University, Shanghai, China
| |
Collapse
|
14
|
Vu C, Shen J, Gonzalez Zacarias C, Xu B, Baas K, Choi S, Nederveen A, Wood JC. Contrast-free dynamic susceptibility contrast using sinusoidal and bolus oxygenation challenges. NMR IN BIOMEDICINE 2024; 37:e5111. [PMID: 38297919 PMCID: PMC10987281 DOI: 10.1002/nbm.5111] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Academic Contribution Register] [Received: 09/07/2023] [Revised: 12/10/2023] [Accepted: 01/08/2024] [Indexed: 02/02/2024]
Abstract
Deoxygenation-based dynamic susceptibility contrast (dDSC) MRI uses respiratory challenges as a source of endogenous contrast as an alternative to gadolinium injection. These gas challenges induce T2*-weighted MRI signal losses, after which tracer kinetics modeling was applied to calculate cerebral perfusion. This work compares three gas challenges, desaturation (transient hypoxia), resaturation (transient normoxia), and SineO2 (sinusoidal modulation of end-tidal oxygen pressures) in a cohort of 10 healthy volunteers (age 37 ± 11 years; 60% female). Perfusion estimates consisted of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). Calculations were computed using a traditional tracer kinetics model in the time domain for desaturation and resaturation and in the frequency domain for SineO2. High correlations and limits of agreement were observed among the three deoxygenation-based paradigms for CBV, although MTT and CBF estimates varied with the hypoxic stimulus. Cross-modality correlation with gadolinium DSC was lower, particularly for MTT, but on a par with agreement between the other perfusion references. Overall, this work demonstrated the feasibility and reliability of oxygen respiratory challenges to measure brain perfusion. Additional work is needed to assess the utility of dDSC in the diagnostic evaluation of various pathologies such as ischemic strokes, brain tumors, and neurodegenerative diseases.
Collapse
Affiliation(s)
- Chau Vu
- Department of Biomedical Engineering, University of Southern California, Los Angeles, California, USA
| | - Jian Shen
- Department of Biomedical Engineering, University of Southern California, Los Angeles, California, USA
| | - Clio Gonzalez Zacarias
- Neuroscience Graduate Program, University of Southern California, Los Angeles, California, USA
| | - Botian Xu
- Department of Biomedical Engineering, University of Southern California, Los Angeles, California, USA
| | - Koen Baas
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location AMC, Amsterdam, Netherlands
| | - Soyoung Choi
- Neuroscience Graduate Program, University of Southern California, Los Angeles, California, USA
| | - Aart Nederveen
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location AMC, Amsterdam, Netherlands
| | - John C. Wood
- Department of Biomedical Engineering, University of Southern California, Los Angeles, California, USA
- Division of Cardiology, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, California, USA
| |
Collapse
|
15
|
Zhao ML, Lu ZJ, Yang L, Ding S, Gao F, Liu YZ, Yang XL, Li X, He SY. The cardiovascular system at high altitude: A bibliometric and visualization analysis. World J Cardiol 2024; 16:199-214. [PMID: 38690218 PMCID: PMC11056872 DOI: 10.4330/wjc.v16.i4.199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 11/22/2023] [Revised: 02/14/2024] [Accepted: 04/01/2024] [Indexed: 04/23/2024] Open
Abstract
BACKGROUND When exposed to high-altitude environments, the cardiovascular system undergoes various changes, the performance and mechanisms of which remain controversial. AIM To summarize the latest research advancements and hot research points in the cardiovascular system at high altitude by conducting a bibliometric and visualization analysis. METHODS The literature was systematically retrieved and filtered using the Web of Science Core Collection of Science Citation Index Expanded. A visualization analysis of the identified publications was conducted employing CiteSpace and VOSviewer. RESULTS A total of 1674 publications were included in the study, with an observed annual increase in the number of publications spanning from 1990 to 2022. The United States of America emerged as the predominant contributor, while Universidad Peruana Cayetano Heredia stood out as the institution with the highest publication output. Notably, Jean-Paul Richalet demonstrated the highest productivity among researchers focusing on the cardiovascular system at high altitude. Furthermore, Peter Bärtsch emerged as the author with the highest number of cited articles. Keyword analysis identified hypoxia, exercise, acclimatization, acute and chronic mountain sickness, pulmonary hypertension, metabolism, and echocardiography as the primary research hot research points and emerging directions in the study of the cardiovascular system at high altitude. CONCLUSION Over the past 32 years, research on the cardiovascular system in high-altitude regions has been steadily increasing. Future research in this field may focus on areas such as hypoxia adaptation, metabolism, and cardiopulmonary exercise. Strengthening interdisciplinary and multi-team collaborations will facilitate further exploration of the pathophysiological mechanisms underlying cardiovascular changes in high-altitude environments and provide a theoretical basis for standardized disease diagnosis and treatment.
Collapse
Affiliation(s)
- Mao-Lin Zhao
- Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, College of Medicine, Southwest Jiaotong University, Chengdu 610083, Sichuan Province, China
| | - Zhong-Jie Lu
- Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, College of Medicine, Southwest Jiaotong University, Chengdu 610083, Sichuan Province, China
| | - Li Yang
- Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, College of Medicine, Southwest Jiaotong University, Chengdu 610083, Sichuan Province, China
| | - Sheng Ding
- Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, College of Medicine, Southwest Jiaotong University, Chengdu 610083, Sichuan Province, China
| | - Feng Gao
- Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, College of Medicine, Southwest Jiaotong University, Chengdu 610083, Sichuan Province, China
| | - Yuan-Zhang Liu
- Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, College of Medicine, Southwest Jiaotong University, Chengdu 610083, Sichuan Province, China
| | - Xue-Lin Yang
- Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, College of Medicine, Southwest Jiaotong University, Chengdu 610083, Sichuan Province, China
| | - Xia Li
- Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, College of Medicine, Southwest Jiaotong University, Chengdu 610083, Sichuan Province, China
| | - Si-Yi He
- Department of Cardiovascular Surgery, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China.
| |
Collapse
|
16
|
Xie J, Xie S, Zhong Z, Dong H, Huang P, Zhou S, Tian H, Zhang J, Wu Y, Li P. Hypoxic preacclimatization combining intermittent hypoxia exposure with physical exercise significantly promotes the tolerance to acute hypoxia. Front Physiol 2024; 15:1367642. [PMID: 38633296 PMCID: PMC11021865 DOI: 10.3389/fphys.2024.1367642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 01/11/2024] [Accepted: 03/19/2024] [Indexed: 04/19/2024] Open
Abstract
Background: Both hypoxia exposure and physical exercise before ascending have been proved to promote high altitude acclimatization, whether the combination of these two methods can bring about a better effect remains uncertain. Therefore, we designed this study to evaluate the effect of hypoxic preacclimatization combining intermittent hypoxia exposure (IHE) and physical exercise on the tolerance to acute hypoxia and screen the optimal preacclimatization scheme among the lowlanders. Methods: A total of 120 Han Chinese young men were enrolled and randomly assigned into four groups, including the control group and three experimental groups with hypoxic preacclimatization of 5-day rest, 5-day exercise, and 3-day exercise in a hypobaric chamber, respectively. Main physical parameters for hypoxia acclimatization, AMS incidence, physical and mental capacity were measured for each participant in the hypobaric chamber simulated to the altitude of 4500 m in the effect evaluation stage. The effect was compared between different schemes. Results: During the effect evaluation stage, SpO2 of the 5-day rest group and 5-day exercise group was significantly higher than that of the control group (p = 0.001 and p = 0.006, respectively). The participants with 5-day rest had significantly lower HR than the controls (p = 0.018). No significant differences of AMS incidence were found among the four groups, while the proportion of AMS headache symptom (moderate and severe vs. mild) was significantly lower in the 3-day exercise group than that in the control group (p = 0.002). The 5-day exercise group had significantly higher VO2max, than the other three groups (p = 0.033, p < 0.001, and p = 0.023, respectively). The 5-day exercise group also had significantly higher digital symbol and pursuit aiming test scores, while shorter color selection reaction time than the control group (p = 0.005, p = 0.005, and p = 0.004, respectively). Conclusion: Hypoxic preacclimatization combining IHE with physical exercise appears to be efficient in promoting the tolerance to acute hypoxia. Hypoxia duration and physical exercise of moderate intensity are helpful for improvement of SpO2 and HR, relief of AMS headache symptoms, and enhancement of mental and physical operation capacity.
Collapse
Affiliation(s)
- Jiaxin Xie
- Department of High Altitude Operational Medicine, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| | - Shenwei Xie
- Department of Health Management, The 953rd Hospital of PLA, Shigatse, China
| | - Zhifeng Zhong
- Department of High Altitude Operational Medicine, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| | - Huaping Dong
- Department of High Altitude Operational Medicine, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| | - Pei Huang
- Department of High Altitude Operational Medicine, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| | - Simin Zhou
- Department of High Altitude Operational Medicine, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| | - Huaijun Tian
- Department of High Altitude Operational Medicine, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| | - Jijian Zhang
- Department of High Altitude Operational Medicine, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| | - Yu Wu
- Department of High Altitude Operational Medicine, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| | - Peng Li
- Department of High Altitude Operational Medicine, College of High Altitude Military Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| |
Collapse
|
17
|
Burtscher J, Raberin A, Brocherie F, Malatesta D, Manferdelli G, Citherlet T, Krumm B, Bourdillon N, Antero J, Rasica L, Burtscher M, Millet GP. Recommendations for Women in Mountain Sports and Hypoxia Training/Conditioning. Sports Med 2024; 54:795-811. [PMID: 38082199 PMCID: PMC11052836 DOI: 10.1007/s40279-023-01970-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Accepted: 11/06/2023] [Indexed: 04/28/2024]
Abstract
The (patho-)physiological responses to hypoxia are highly heterogeneous between individuals. In this review, we focused on the roles of sex differences, which emerge as important factors in the regulation of the body's reaction to hypoxia. Several aspects should be considered for future research on hypoxia-related sex differences, particularly altitude training and clinical applications of hypoxia, as these will affect the selection of the optimal dose regarding safety and efficiency. There are several implications, but there are no practical recommendations if/how women should behave differently from men to optimise the benefits or minimise the risks of these hypoxia-related practices. Here, we evaluate the scarce scientific evidence of distinct (patho)physiological responses and adaptations to high altitude/hypoxia, biomechanical/anatomical differences in uphill/downhill locomotion, which is highly relevant for exercising in mountainous environments, and potentially differential effects of altitude training in women. Based on these factors, we derive sex-specific recommendations for mountain sports and intermittent hypoxia conditioning: (1) Although higher vulnerabilities of women to acute mountain sickness have not been unambiguously shown, sex-dependent physiological reactions to hypoxia may contribute to an increased acute mountain sickness vulnerability in some women. Adequate acclimatisation, slow ascent speed and/or preventive medication (e.g. acetazolamide) are solutions. (2) Targeted training of the respiratory musculature could be a valuable preparation for altitude training in women. (3) Sex hormones influence hypoxia responses and hormonal-cycle and/or menstrual-cycle phases therefore may be factors in acclimatisation to altitude and efficiency of altitude training. As many of the recommendations or observations of the present work remain partly speculative, we join previous calls for further quality research on female athletes in sports to be extended to the field of altitude and hypoxia.
Collapse
Affiliation(s)
- Johannes Burtscher
- Institute of Sport Sciences, Faculty of Biology and Medicine, University of Lausanne, Building Synathlon, Campus Dorigny, 1015, Lausanne, Switzerland
| | - Antoine Raberin
- Institute of Sport Sciences, Faculty of Biology and Medicine, University of Lausanne, Building Synathlon, Campus Dorigny, 1015, Lausanne, Switzerland
| | - Franck Brocherie
- Laboratory Sport, Expertise and Performance (EA 7370), French Institute of Sport, Paris, France
| | - Davide Malatesta
- Institute of Sport Sciences, Faculty of Biology and Medicine, University of Lausanne, Building Synathlon, Campus Dorigny, 1015, Lausanne, Switzerland
| | - Giorgio Manferdelli
- Institute of Sport Sciences, Faculty of Biology and Medicine, University of Lausanne, Building Synathlon, Campus Dorigny, 1015, Lausanne, Switzerland
| | - Tom Citherlet
- Institute of Sport Sciences, Faculty of Biology and Medicine, University of Lausanne, Building Synathlon, Campus Dorigny, 1015, Lausanne, Switzerland
| | - Bastien Krumm
- Institute of Sport Sciences, Faculty of Biology and Medicine, University of Lausanne, Building Synathlon, Campus Dorigny, 1015, Lausanne, Switzerland
| | - Nicolas Bourdillon
- Institute of Sport Sciences, Faculty of Biology and Medicine, University of Lausanne, Building Synathlon, Campus Dorigny, 1015, Lausanne, Switzerland
| | - Juliana Antero
- Institut de Recherche Bio-Médicale Et d'Épidémiologie du Sport (EA 7329), French Institute of Sport, Paris, France
| | - Letizia Rasica
- Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada
| | - Martin Burtscher
- Department of Sport Science, University of Innsbruck, Innsbruck, Austria
| | - Grégoire P Millet
- Institute of Sport Sciences, Faculty of Biology and Medicine, University of Lausanne, Building Synathlon, Campus Dorigny, 1015, Lausanne, Switzerland.
| |
Collapse
|
18
|
Tenzing D, Suolang P, Gesang D, Suolang D, Duan G, Ciren W, Wang Y, Ni T. Effect of furosemide in the treatment of high-altitude pulmonary edema. BMC Pulm Med 2024; 24:109. [PMID: 38438895 PMCID: PMC10913242 DOI: 10.1186/s12890-024-02933-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 12/15/2023] [Accepted: 02/26/2024] [Indexed: 03/06/2024] Open
Abstract
BACKGROUND High-altitude pulmonary edema (HAPE) refers to the onset of breathlessness, cough, and fever at rest after arriving at high altitudes. It is a life-threatening illness caused by rapid ascent to high altitudes. Furosemide is controversial in HAPE treatment but is routinely used in China. Further research is needed to assess its efficacy and impact on HAPE management and prognosis. The aim of this study is to determine the effectiveness of furosemide for HAPE. METHODS A retrospective was conducted to analysis of patients with HAPE admitted to the People's Hospital of Shigatse City from January 2018 to September 2023. Patients were divided into furosemide group and non-furosemide group for further analysis. Clinical variables including demographic information, comorbidities, vital signs, inflammatory markers, biochemical analysis, CT severity score and prognostic indicators were collected. RESULTS A total of 273 patients were enrolled, with 209 patients in the furosemide group and 64 patients in the non-furosemide group. The furosemide group showed a significantly decrease in CT severity scores compared to the non-furosemide group. Subgroup analysis showed that the longer the duration of furosemide use, the more pronounced the improvement in lung CT severity scores. But there were no significant differences in length of hospital stay and in-hospital mortality between the two groups. CONCLUSION Furosemide helps alleviate pulmonary edema in HAPE patients, but further research is needed to clarify its impact on prognosis.
Collapse
Affiliation(s)
- Dava Tenzing
- Department of Emergency, People's Hospital of Shigatse City, No. 1 Daqing East Road, Sangzhuzi District, Shigatse City, Tibet, China
| | - Pianduo Suolang
- Department of Emergency, People's Hospital of Shigatse City, No. 1 Daqing East Road, Sangzhuzi District, Shigatse City, Tibet, China
| | - Deji Gesang
- Department of Emergency, People's Hospital of Shigatse City, No. 1 Daqing East Road, Sangzhuzi District, Shigatse City, Tibet, China
| | - Duoji Suolang
- Department of Emergency, People's Hospital of Shigatse City, No. 1 Daqing East Road, Sangzhuzi District, Shigatse City, Tibet, China
| | - Gaozhan Duan
- Department of Emergency, People's Hospital of Shigatse City, No. 1 Daqing East Road, Sangzhuzi District, Shigatse City, Tibet, China
| | - Wangmu Ciren
- Department of Emergency, People's Hospital of Shigatse City, No. 1 Daqing East Road, Sangzhuzi District, Shigatse City, Tibet, China
| | - Yihui Wang
- Department of Emergency, People's Hospital of Shigatse City, No. 1 Daqing East Road, Sangzhuzi District, Shigatse City, Tibet, China.
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin er Road, Huangpu District, 200025, Shanghai, China.
| | - Tongtian Ni
- Department of Emergency, People's Hospital of Shigatse City, No. 1 Daqing East Road, Sangzhuzi District, Shigatse City, Tibet, China.
- Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin er Road, Huangpu District, 200025, Shanghai, China.
| |
Collapse
|
19
|
Han C, Zheng XX, Zhang WF. High altitude retinopathy: An overview and new insights. Travel Med Infect Dis 2024; 58:102689. [PMID: 38295966 DOI: 10.1016/j.tmaid.2024.102689] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 09/01/2023] [Revised: 12/30/2023] [Accepted: 01/15/2024] [Indexed: 02/04/2024]
Abstract
High altitude retinopathy (HAR) is a common ocular disorder that occurs on ascent to high altitude. There are many clinical symptoms, retinal vascular dilatation, retinal edema and hemorrhage are common. These usually do not or slightly affect vision; rarely, severe cases develop serious or permanent vision loss. At present, the research progress of HAR mainly focuses on hemodynamic changes, blood-retinal barrier damage, oxidative stress and inflammatory response. Although the related studies on HAR are limited, it shows that HAR still belongs to hypoxia, and hypobaric hypoxia plays an aggravating role in promoting the development of the disease. Various studies have demonstrated the correlation of HAR with acute mountain sickness (AMS) and high-altitude cerebral edema (HACE), so a deeper understanding of HAR is important. The slow ascent rates and ascent altitude are the key to preventing any altitude sickness. Research on traditional chinese medicine (TCM) and western medicine has been gradually carried out. Further exploration of the pathogenesis and prevention strategies of HAR will provide better guidance for doctors and high-altitude travelers.
Collapse
Affiliation(s)
- Cong Han
- Department of Ophthalmology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730000, Gansu, PR China.
| | - Xing-Xing Zheng
- Department of Ophthalmology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730000, Gansu, PR China.
| | - Wen-Fang Zhang
- Department of Ophthalmology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730000, Gansu, PR China.
| |
Collapse
|
20
|
Dang ZC, Yang Z, Liu S, Du GM, Jin L, Zhao ZZ. Efficacy of Sildenafil on healthy humans in high‑altitude hypoxia at rest and during exercise: A meta‑analysis. Exp Ther Med 2024; 27:88. [PMID: 38274336 PMCID: PMC10809317 DOI: 10.3892/etm.2024.12376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 05/30/2023] [Accepted: 10/23/2023] [Indexed: 01/27/2024] Open
Abstract
The current meta-analysis aimed to fully evaluate the efficacy of Sildenafil in healthy humans at different altitudes, focusing on echocardiographic and hemodynamic parameters. Relevant studies were retrieved from the Cochrane, Embase and PubMed databases. Odds ratios (OR) were determined for dichotomous data and weighted mean differences with 95% confidence intervals (CIs) for continuous data. A total of 16 RCTs were included in the current meta-analysis. Short-term treatment with Sildenafil significantly elevated resting heart rate (P<0.01) at altitudes <4,000 meters. No significant differences in heart rate were observed between the Sildenafil and placebo groups at rest and during exercise at an altitude of >4,000 meters (P>0.05). Sildenafil improved resting cardiac output at an altitude of >5,000 meters (P<0.01) and exercising arterial oxygen saturation at <4,000 meters (P<0.01). Sildenafil reduced resting pulmonary artery systolic pressure (PASP) at altitudes >4,000 meters (P<0.01) and exercising PASP at altitudes >5,000 meters (P<0.01). Therefore, Sildenafil efficacy in healthy humans with high-altitude hypoxia is related to altitude and rest or exercise.
Collapse
Affiliation(s)
- Zhan-Cui Dang
- Department of Public Health, Medical College, Qinghai University, Xining, Qinghai 810000, P.R. China
| | - Zhiquan Yang
- Department of Rehabilitation, Women and Children's Hospital of Qinghai Province, Xining, Qinghai 810000, P.R. China
| | - Shou Liu
- Department of Public Health, Medical College, Qinghai University, Xining, Qinghai 810000, P.R. China
| | - Guo-Mei Du
- Department of Physical Examination, Qinghai Red Cross Hospital, Xining, Qinghai 810000, P.R. China
| | - Linde Jin
- Department of Cardiology, Qinghai Provincial People's Hospital, Xining, Qinghai 810000, P.R. China
| | - Zhong-Zhi Zhao
- Department of Endemic Disease Control, Qinghai Provincial Institute for Endemic Disease Prevention and Control, Xining, Qinghai 811602, P.R. China
| |
Collapse
|
21
|
Yang X, Dong X, Li J, Zheng A, Shi W, Shen C, Liu J. Nanocurcumin attenuates pyroptosis and inflammation through inhibiting NF-κB/GSDMD signal in high altitude-associated acute liver injury. J Biochem Mol Toxicol 2024; 38:e23606. [PMID: 38050447 DOI: 10.1002/jbt.23606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 05/07/2022] [Revised: 07/12/2023] [Accepted: 11/21/2023] [Indexed: 12/06/2023]
Abstract
Exposure to a hypobaric hypoxic environment at high altitudes can lead to liver injury, and mounting evidence indicates that pyroptosis and inflammation play important roles in liver injury. Curcumin (Cur) can inhibit pyroptosis and inflammation. Therefore, our purpose here was to clarify the mechanism underlying the protective effect of nanocurcumin (Ncur) and Cur in a rat model of high altitude-associated acute liver injury. Eighty healthy rats were selected and exposed to different altitudes (6000 or 7000 m) for 0, 24, 48, or 72 h. Fifty normal healthy rats were divided into normal control, high-altitude control, salidroside (40 mg/kg [Sal-40]), Cur (200 mg/kg [Cur-200]), and Ncur (25 mg/kg [Ncur-25]) groups and exposed to a high-altitude hypobaric hypoxic environment (48 h, 7000 m). Serum-liver enzyme activities (alanine transaminase, aspartate transaminase, and lactate dehydrogenase were detected and histopathology of liver injury was evaluated by hematoxylin and eosin staining, and inflammatory factors were detected in liver tissues by enzyme-linked immunosorbent assays. Pyroptosis-associated proteins (gasdermin D, gasdermin D N-terminal [GSDMD-N], pro-Caspase-1, and cleaved-Caspase-1 [cleaved-Casp1]) and inflammation-associated proteins (nuclear factor-κB [NF-κB], phospho-NF-κB [P-NF-κB], and high-mobility group protein B1 [HMGB1]) levels were analyzed by immunoblotting. Ncur and Cur inhibited increased serum-liver enzyme activities, alleviated liver injury in rats caused by high-altitude hypobaric hypoxic exposure, and downregulated inflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-18, in rat liver tissues. The level of P-NF-κB, GSDMD-N, cleaved-Casp1, and HMGB1 in rat liver tissues increased significantly after high-altitude exposure. Ncur and Cur downregulated P-NF-κB, GSDMD-N, cleaved-Casp-1, and HMGB1. Ncur and Cur may inhibit inflammatory responses and pyroptosis in a rat model of high altitude-associated acute liver injury.
Collapse
Affiliation(s)
- Xinyue Yang
- Key Laboratory of Special Environmental Medicine of Xinjiang, General Hospital of Xinjang Military Command, Urumqi, China
- Graduate School, Xinjiang Medical University, Urumqi, China
| | - Xiang Dong
- Graduate School, Xinjiang Medical University, Urumqi, China
| | - Jiajia Li
- Graduate School, Xinjiang Medical University, Urumqi, China
| | - Aiping Zheng
- Institute of Pharmacology and Toxicology, Academy of Military Medicine, Beijing, China
| | - Wenhui Shi
- Graduate School, Xinjiang Medical University, Urumqi, China
| | - Caifu Shen
- Graduate School, Xinjiang Medical University, Urumqi, China
| | - Jiangwei Liu
- Graduate School, Xinjiang Medical University, Urumqi, China
| |
Collapse
|
22
|
Zhang J, Wen Y, Yin Y, Zhang Y, Zhang R, Zhang X, Ye J, Feng Y, Meng H. Impression life with pulmonary hypertension: clinically relevant characteristics and quality of life among patients in Gansu, China. Ther Adv Respir Dis 2024; 18:17534666241246428. [PMID: 38676370 PMCID: PMC11055475 DOI: 10.1177/17534666241246428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 05/23/2023] [Accepted: 03/22/2024] [Indexed: 04/28/2024] Open
Abstract
BACKGROUND The adverse effects of pulmonary arterial hypertension (PAH) on physical, emotional, and health-related quality of life (HRQoL) remain primarily unrecognized, especially in resource-limited settings. OBJECTIVES This study aims to characterize the HRQoL of patients with PAH in this area and also identify the potential role of clinically relevant characteristics, including the 6-min walk distance test (6MWD), WHO-Functional Classification (WHO-FC), and mental health in the occurrence of lowering quality of life. DESIGN This was a cross-sectional observational study. METHODS Inpatients with PAH were chosen from a tertiary hospital located in Gansu province, China. All participants were interviewed face-by-face by using questionnaires, including items from the 36-Item Short Form Health Survey (SF-36), the self-rating anxiety scale, and the self-rating depression scale. Data on demographic and clinically relevant characteristics, including WHO-FC and 6MWD, were also collected by tracing medical recorders. Multiple linear regression analysis was used to determine the association between demographic, clinically relevant characteristics data, and physical component summary (PCS) or mental component summary (MCS) in SF-36. RESULTS Of the 152 participants, SF-36 differed significantly from Chinese norms in all eight domains, with role-physical (21.55 ± 9.87) less than one-third of the norm (88.79 ± 28.49). Multiple linear regression results showed that the factors with the greatest impact on PCS were anxiety scores (β = -0.22, p = 0.001), followed by WHO-FC (β = -0.16, p = 0.014) and 6MWD (β = 0.15, p = 0.036). The factors with the greatest impact on MCS were WHO-FC (β = -0.30, p < 0.001), followed by anxiety (β = -0.23, p = 0.001) and depression scores (β = -0.16, p = 0.013). CONCLUSION HRQoL was substantially reduced among PAH patients in the resource-limited area, mainly the physiological functions. WHO-FC and anxiety scores were independently associated with both PCS and MCS in SF-36. Clinicians should make reasonable rehabilitation programs and plans for patients according to their cardiac function grade and the severity of clinical symptoms. In addition, psychological interventions should also be taken, especially for those with anxiety symptoms, so as to improve their HRQoL.
Collapse
Affiliation(s)
- Juxia Zhang
- Clinical Educational Department, Gansu Provincial Hospital, Lanzhou, Gansu 730000, China
| | - Yujie Wen
- Cardiovascular Department, Gansu Provincial Hospital, Lanzhou, Gansu, China
| | - Yuhuan Yin
- School of Nursing, Gansu University of Chinese Medicine, Lanzhou, Gansu, China
| | - Yiyin Zhang
- School of Nursing, Gansu University of Chinese Medicine, Lanzhou, Gansu, China
| | - Rong Zhang
- School of Nursing, Gansu University of Chinese Medicine, Lanzhou, Gansu, China
| | - Xiaoli Zhang
- School of Nursing, Gansu University of Chinese Medicine, Lanzhou, Gansu, China
| | - Jianying Ye
- School of Nursing, Gansu University of Chinese Medicine, Lanzhou, Gansu, China
| | - Yuping Feng
- School of Nursing, Gansu University of Chinese Medicine, Lanzhou, Gansu, China
| | - Hongyan Meng
- School of Nursing, Gansu University of Chinese Medicine, Lanzhou, Gansu, China
| |
Collapse
|
23
|
Liu D, Gao X, Huang X, Fan Y, Wang YE, Zhang Y, Chen X, Wen J, He H, Hong Y, Liang Y, Zhang Y, Liu Z, Chen S, Li X. Moderate altitude exposure impacts host fasting blood glucose and serum metabolome by regulation of the intestinal flora. THE SCIENCE OF THE TOTAL ENVIRONMENT 2023; 905:167016. [PMID: 37714338 DOI: 10.1016/j.scitotenv.2023.167016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Academic Contribution Register] [Received: 03/29/2023] [Revised: 09/09/2023] [Accepted: 09/10/2023] [Indexed: 09/17/2023]
Abstract
Moderate altitude exposure has shown beneficial effects on diabetes incidence but the underlying mechanisms are not understood. Our study aimed to investigate how the human gut microbiome impacted the serum metabolome and associated with glucose homeostasis in healthy Chinese individuals upon moderate-altitude exposure. Faecal microbiome composition was assessed using shotgun metagenomic sequencing. Serum metabolome was acquired by untargeted metabolomics technology, and amino acids (AAs) and propionic acid in serum were quantified by targeted metabolomics technology. The results indicated that the moderate-altitude exposed individuals presented lowered fasting blood glucose (FBG) and propionic acid, increased circulating L-Glutamine but decreased L-Glutamate and L-Valine, which correlated with enriched Bacteroidetes and decreased Proteobacteria. Additionally, the silico causality associations among gut microbiota, serum metabolome and host FBG were analyzed by mediation analysis. It showed that increased Bacteroides ovatus (B. ovatus) and decreased Escherichia coli (E. coli) were identified as the main antagonistic species driving the association between L-Glutamate and FBG in silico causality. Furthermore, the high-fat diet (HFD) fed mice subjected to faecal microbiota transplantation (FMT) were applied to validate the cause-in-fact effects of gut microbiota on the beneficial glucose response. We found that microbiome in the moderate-altitude exposed donor could predict the extent of the FBG response in recipient mice, which showed lowered FBG, L-Glutamate and Firmicutes/Bacteroidetes ratio. Our findings suggest that moderate-altitude exposure targeting gut microbiota and circulating metabolome, may pave novel avenues to counter dysglycemia.
Collapse
Affiliation(s)
- Dan Liu
- Department of Emergency Medicine, Guangdong Provincial People's Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China; Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Nyingchi People's Hospital, Tibet, China
| | - Xiaoyan Gao
- Department of Emergency Medicine, Guangdong Provincial People's Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China; School of Medicine, South China University of Technology, Guangzhou, China
| | - Xiaoran Huang
- Department of Emergency Medicine, Guangdong Provincial People's Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Yanqun Fan
- Biotree Metabolomics Technology Research Center, Shanghai, China
| | - Yu-E Wang
- Nyingchi People's Hospital, Tibet, China
| | - Yuelin Zhang
- Department of Emergency Medicine, Guangdong Provincial People's Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Xuanfu Chen
- Department of Emergency Medicine, Guangdong Provincial People's Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China; Emergency Medicine Department of Guangdong Cardiovascular Institute, Guangzhou, China
| | - Jielu Wen
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-Sen Memorial Hospital, Foshan, China
| | - Haiwei He
- Department of Emergency Medicine, Guangdong Provincial People's Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Yimei Hong
- Department of Emergency Medicine, Guangdong Provincial People's Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Ying Liang
- Department of Emergency Medicine, Guangdong Provincial People's Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China; Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Nyingchi People's Hospital, Tibet, China
| | - Yuxiao Zhang
- Department of Emergency Medicine, Guangdong Provincial People's Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China; School of Medicine, South China University of Technology, Guangzhou, China
| | - Zhipeng Liu
- Biotree Metabolomics Technology Research Center, Shanghai, China.
| | - Sifan Chen
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-Sen Memorial Hospital, Foshan, China.
| | - Xin Li
- Department of Emergency Medicine, Guangdong Provincial People's Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China; Nyingchi People's Hospital, Tibet, China.
| |
Collapse
|
24
|
Zhang J, Meng H, Yin Y, Zhang Y, Wen Y, Zhang R, Wang J. Prevalence and Determinants of Delay in Time-to-Diagnosis for Pulmonary Arterial Hypertension Patients in Gansu China: A Observational Cohort Study. Curr Probl Cardiol 2023; 48:102026. [PMID: 37553061 DOI: 10.1016/j.cpcardiol.2023.102026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 08/04/2023] [Accepted: 08/04/2023] [Indexed: 08/10/2023]
Abstract
Current studies of patients with pulmonary arterial hypertension (PAH) have shown a significant diagnostic delay. However, the causes and risk factors for this delay are not been well explored in Chinese population. This study aimed to assess the status of diagnostic delay in patients with PAH in China. Additionally, we identified factors associated with the delay. Demographic and clinical data were collected from 153 PAH patients admitted to three tertiary hospitals in Gansu, China, from March 2020 to October 2022. Based on the recorded date, the diagnostic delay was divided into patient delay and health system delay. For analysis, we divided diagnostic delay into 2 groups (≤3 years and >3 years). Factors associated with delay were identified by binary logistic regression. The median diagnostic delay was 3 years (IQR: 0.25-5.88). Binary logistic regression analysis showed that male (OR = 2.48, 95% CI: 1.10-5.58), those with junior high school or below (OR = 3.65, 95% CI: 1.36-9.78), living far away from the tertiary hospital (OR = 2.66, 95% CI: 1.14-6.18), initially visit hospital before 2018 (OR = 3.82, 95% CI: 1.68-8.71), and visit hospital at county level or below (OR = 3.80, 95% CI: 1.42-10.18) were risk factor for diagnostic delay (>3 years). Despite increased awareness, most patients with PAH in Gansu, China still experienced a delay in diagnosis of more than 3 years. Male sex, lower educational background, and being away from tertiary hospitals are risk factors for delay. Furthermore, factors impacting time-to-diagnosis and its impact should be continuously evaluated as therapeutic strategies continue to evolve and improve.
Collapse
Affiliation(s)
- Juxia Zhang
- Clinical Educational Department, Gansu Provincial Hospital, Lanzhou, Gansu, China
| | - Hongyan Meng
- School of Nursing, Gansu University of Chinese Medicine, Lanzhou, Gansu, China
| | - Yuhuan Yin
- Department of Thoracic Surgery, The Second Affiliated Hospital of Air Force Medical University, Xi'an, China
| | - Yiyin Zhang
- School of Nursing, Gansu University of Chinese Medicine, Lanzhou, Gansu, China
| | - Yujie Wen
- Department of Cardiology, Gansu Provincial Hospital, Lanzhou, Gansu, China
| | - Rong Zhang
- School of Nursing, Gansu University of Chinese Medicine, Lanzhou, Gansu, China
| | - Jiancheng Wang
- Department of General Practice Medicine, Hospital of Gansu health vocational college, Lanzhou, Gansu, China.
| |
Collapse
|
25
|
Dou L, Shi Z, Cuomu Z, Zhuoga C, Li C, Dawa Z, Li S. Health-related quality of life and its changes of the Tibetan population in China: based on the 2013 and 2018 National Health Services Surveys. BMJ Open 2023; 13:e072854. [PMID: 37984958 PMCID: PMC10660197 DOI: 10.1136/bmjopen-2023-072854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 02/17/2023] [Accepted: 10/25/2023] [Indexed: 11/22/2023] Open
Abstract
OBJECTIVE Health-related quality of life (HRQoL) was an important health outcome measure for evaluating an individual's overall health status. However, there was limited in the literature on HRQoL and its long-term changes of the Tibetan population. This study aimed to assess HRQoL of Tibetan and its changes over time, and explore the differences in HRQoL for residents at different altitudes. DESIGN Data for the cross-sectional study were extracted from the fifth and sixth waves of the National Health Services Surveys which were conducted in 2013 and 2018. A multistage stratified cluster random sampling strategy was used to select representative participants. SETTING Tibet Autonomous Region in China. PARTICIPANTS This study recruited 14 752 participants in 2013 and 13 106 participants in 2018, and after excluding observations with missing values for key variables, 10 247 in 2013 and 6436 in 2018 were included in the study analysis. PRIMARY AND SECONDARY OUTCOME MEASURES The EQ-5D-3L was used to measure participants' HRQoL. RESULTS The mean health state utility scores of the participants were 0.969±0.078 and 0.966±0.077 in 2013 and 2018, respectively. Pain/discomfort was the most frequently prevalent issue reported in 18.1% and 17.9% of the participants in 2013 and 2018, respectively. Tibetans living 3500-4000 m altitude had the best HRQoL. Age, sex, employment status, educational attainment, chronic disease and weekly physical exercise were influencing factors associated with HRQoL. CONCLUSIONS The HRQoL of the Tibetan population was lower than the general Chinese population, and decreased over time between 5 years. There were differences in HRQoL among Tibetan at different altitudes, with residents living at 3500-4000 m having the best quality of life. More attention should be paid to those Tibetans who are older, female, unemployed and without formal education.
Collapse
Affiliation(s)
- Lei Dou
- Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
- NHC Key Lab of Health Economics and Policy Research (Shandong University), Jinan, China
- Center for Health Preference Research, Shandong University, Jinan, China
| | - Zhao Shi
- Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
- NHC Key Lab of Health Economics and Policy Research (Shandong University), Jinan, China
- Center for Health Preference Research, Shandong University, Jinan, China
| | - Zhaxi Cuomu
- Medical College of Tibet University, Lhasa, China
- Center of Tibetan Studies (Everest Research Institute), Tibet University, Lhasa, China
| | - Cidan Zhuoga
- Medical College of Tibet University, Lhasa, China
- Center of Tibetan Studies (Everest Research Institute), Tibet University, Lhasa, China
| | - Chaofan Li
- Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
- NHC Key Lab of Health Economics and Policy Research (Shandong University), Jinan, China
- Center for Health Preference Research, Shandong University, Jinan, China
| | - Zhaxi Dawa
- Medical College of Tibet University, Lhasa, China
- Center of Tibetan Studies (Everest Research Institute), Tibet University, Lhasa, China
| | - Shunping Li
- Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
- NHC Key Lab of Health Economics and Policy Research (Shandong University), Jinan, China
- Center for Health Preference Research, Shandong University, Jinan, China
| |
Collapse
|
26
|
Zheng B, Luo Y, Li Y, Gu G, Jiang J, Chen C, Chen Z, Wang J. Prevalence and risk factors of stroke in high-altitude areas: a systematic review and meta-analysis. BMJ Open 2023; 13:e071433. [PMID: 37734891 PMCID: PMC10514645 DOI: 10.1136/bmjopen-2022-071433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 01/06/2023] [Accepted: 08/31/2023] [Indexed: 09/23/2023] Open
Abstract
OBJECTIVE The primary objective of this study is to investigate the prevalence and risk factors of stroke in high-altitude areas through a comprehensive systematic review and meta-analysis. DESIGN This study adopts a systematic review and meta-analysis design. DATA SOURCES A thorough search was conducted on databases including PubMed, Web of Science, Embase, Cochrane Library, MEDLINE and SCOPUS, covering the period up to June 2023. ELIGIBILITY CRITERIA Studies reporting the prevalence of stroke in high-altitude areas and exploring related risk factors were included, regardless of whether they involved clinical samples or the general population. Studies with incomplete, outdated or duplicate data were excluded. DATA EXTRACTION AND SYNTHESIS We performed eligibility screening, data extraction and quality evaluation of the retrieved articles. Meta-analysis was employed to estimate the prevalence and risk factors of stroke in high-altitude areas. The Newcastle-Ottawa Scale was used to assess the risk of bias. RESULTS A total of 17 studies encompassing 8 566 042 participants from four continents were included, with altitudes ranging from 1500 m to nearly 5000 m. The pooled prevalence of stroke in high-altitude areas was found to be 0.5% (95% CI 0.3%-7%). Notably, the prevalence was higher in clinical samples (1.2%; 0.4%-2.5%) compared with the general population (0.3%; 95% CI 0.1%-0.6%). When considering geographic regions, the aggregated data indicated that stroke prevalence in the Eurasia plate was 0.3% (0.2%-0.4%), while in the American region, it was 0.8% (0.4%-1.3%). Age (OR, 14.891), gender (OR, 1.289), hypertension (OR, 3.158) and obesity (OR, 1.502) were identified as significant risk factors for stroke in high-altitude areas. CONCLUSIONS The findings of this study provide insights into the pooled prevalence of stroke in high-altitude areas, highlighting variations based on geographic regions and sampling type. Moreover, age, gender, hypertension and obesity were found to be associated with the occurrence of stroke. PROSPERO REGISTRATION NUMBER CRD42022381541.
Collapse
Affiliation(s)
- Bo Zheng
- Department of Neurology, Ya'an Peoples Hospital, Ya'an, People's Republic of China
| | - Yuding Luo
- Department of Neurology, Ya'an Peoples Hospital, Ya'an, People's Republic of China
- Affiliated Hospital of Southwest Medical University, Luzhou, People's Republic of China
| | - Yan Li
- Department of Neurology, Ya'an Peoples Hospital, Ya'an, People's Republic of China
| | - Gangfeng Gu
- Department of Neurology, Ya'an Peoples Hospital, Ya'an, People's Republic of China
| | - Junyao Jiang
- Department of Neurology, Ya'an Peoples Hospital, Ya'an, People's Republic of China
| | - Chuanli Chen
- Department of Neurology, Ya'an Peoples Hospital, Ya'an, People's Republic of China
| | - Zhao Chen
- Department of Neurology, Ya'an Peoples Hospital, Ya'an, People's Republic of China
| | - Jian Wang
- Department of Neurology, Ya'an Peoples Hospital, Ya'an, People's Republic of China
| |
Collapse
|
27
|
Zubieta-Calleja GR, Zubieta-DeUrioste N. High Altitude Pulmonary Edema, High Altitude Cerebral Edema, and Acute Mountain Sickness: an enhanced opinion from the High Andes - La Paz, Bolivia 3,500 m. REVIEWS ON ENVIRONMENTAL HEALTH 2023; 38:327-338. [PMID: 35487499 DOI: 10.1515/reveh-2021-0172] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Academic Contribution Register] [Received: 12/20/2021] [Accepted: 03/21/2022] [Indexed: 06/02/2023]
Abstract
Traveling to high altitudes for entertainment or work is sometimes associated with acute high altitude pathologies. In the past, scientific literature from the lowlander point of view was primarily based on mountain climbing. Sea level scientists developed all guidelines, but they need modifications for medical care in high altitude cities. Acute Mountain Sickness, High Altitude Pulmonary Edema, and High Altitude Cerebral Edema are medical conditions that some travelers can face. We present how to diagnose and treat acute high altitude pathologies, based on 51 years of high altitude physiology research and medical practice in hypobaric hypoxic diseases in La Paz, Bolivia (3,600 m; 11,811 ft), at the High Altitude Pulmonary and Pathology Institute (HAPPI - IPPA). These can occasionally present after flights to high altitude cities, both in lowlanders or high-altitude residents during re-entry. Acute high altitude ascent diseases can be adequately diagnosed and treated in high altitude cities following the presented guidelines. Treating these high-altitude illnesses, we had no loss of life. Traveling to a high altitude with sound medical advice should not be feared as it has many benefits. Nowadays, altitude descent and evacuation are not mandatory in populated highland cities, with adequate medical resources.
Collapse
Affiliation(s)
- Gustavo R Zubieta-Calleja
- High Altitude Pulmonary and Pathology Institute (HAPPI-IPPA), La Paz, Bolivia
- Department of Physiology, Shri B.M. Patil Medical College, Hospital and Research Centre, BLDE (Deemed to be University), Vijayapur 586103, Karnataka, India
| | | |
Collapse
|
28
|
Burtscher J, Swenson ER, Hackett PH, Millet GP, Burtscher M. Flying to high-altitude destinations: Is the risk of acute mountain sickness greater? J Travel Med 2023; 30:taad011. [PMID: 36694981 PMCID: PMC10289512 DOI: 10.1093/jtm/taad011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 12/08/2022] [Revised: 12/31/2022] [Accepted: 01/17/2023] [Indexed: 01/26/2023]
Abstract
BACKGROUND Altitude sojourns increasingly attract individuals of all ages and different health statuses due to the appeal of high-altitude destinations worldwide and easy access to air travel. The risk of acute mountain sickness (AMS) when flying to high-altitude destinations remains underemphasized. Thus, this review aims to evaluate the altitude-dependent AMS incidence depending on the mode of ascending, e.g. by air vs terrestrial travel. METHODS A literature search was performed to identify the observational studies assessing AMS incidence after acute ascent of primarily healthy adults to real high altitude. In addition, placebo arms of interventional trials evaluating the prophylactic efficacy of various drugs have been separately analysed to confirm or refute the findings from the observational studies. Linear regression analyses were used to evaluate the altitude-dependent AMS incidence. RESULTS Findings of 12 observational studies, in which the AMS incidence in 11 021 individuals ascending to 19 different altitudes (2200-4559 m) was evaluated, revealed an impressive 4.5-fold steeper increase in the AMS incidence for air travel as compared with slower ascent modes, i.e. hiking or combined car and/or air travel and hiking. The higher AMS incidence following transportation by flight vs slower means was also confirmed in placebo-treated participants in 10 studies of drug prophylaxis against AMS. CONCLUSIONS Due to the short time span in going from low to high altitude, reduced acclimatization likely is the main reason for a higher AMS risk when travelling to high-altitude destinations by flight. To avoid frustrating travel experiences and health risks, appropriate and timely medical advice on how to prepare for air travel to high altitude is of vital importance. Effective preparation options include the use of modern pre-acclimatization strategies and pharmacological prophylaxis by acetazolamide or dexamethasone, or even considering alternate itineraries with more gradual ascent.
Collapse
Affiliation(s)
- Johannes Burtscher
- Institute of Sport Sciences, University of Lausanne, Lausanne 1015, Switzerland
- Department of Biomedical Sciences, University of Lausanne, Lausanne 1005, Switzerland
| | - Erik R Swenson
- VA Puget Health Care System, University of Washington, Seattle, WA, USA
| | - Peter H Hackett
- Altitude Research Center, Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Grégoire P Millet
- Institute of Sport Sciences, University of Lausanne, Lausanne 1015, Switzerland
- Department of Biomedical Sciences, University of Lausanne, Lausanne 1005, Switzerland
| | - Martin Burtscher
- Department of Sport Science, University of Innsbruck, Innsbruck A-6020, Austria
- Austrian Society for Alpine and High-Altitude Medicine, Innsbruck A-6020, Austria
| |
Collapse
|
29
|
Aman M, Alam MS, Khan F, Anwar SSM, Ahmed A, Khan U, Bazai UK. High-altitude cerebral edema manifesting as T2/FLAIR hyperintensity and microbleeds in the white matter on MRI brain. Radiol Case Rep 2023; 18:1705-1709. [PMID: 36895894 PMCID: PMC9989253 DOI: 10.1016/j.radcr.2023.01.071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 12/25/2022] [Revised: 01/16/2023] [Accepted: 01/17/2023] [Indexed: 03/02/2023] Open
Abstract
High-altitude cerebral edema is a rare type of acute mountain illness characterized by consciousness disruption and truncal ataxia. Here we discuss a 40-year-old nondiabetic, nonsmoker male who went on a tour to Nanga Parbat. On returning home, the patient developed symptoms of headache, nausea, and vomiting. His symptoms worsened with time and he developed lower limb weakness and shortness of breath. Later, he underwent a computerized tomography chest scan. On the basis of CT scan findings, the doctors decided that the patient was suffering from COVID-19 Pneumonia despite having negative COVID-19 PCR tests multiple times. Later, the patient presented to our hospital with similar complaints. MRI of the brain revealed T2/fluid-attenuated inversion recovery hyperintense and T1 hypointense signals in the bilateral semioval centrum, posterior periventricular white matter, and corpus callosum genu, body, and splenium. These abnormal signals were discovered to be more evident in the corpus callosum's splenium. Moreover, susceptibility-weighted imaging revealed micro hemorrhages in the corpus callosum. This verified the diagnosis that the patient is suffering from high-altitude cerebral edema. Within 5 days, his symptoms resolved and he was discharged with full recovery.
Collapse
Affiliation(s)
- Muhammad Aman
- Department of Radiology, Aga Khan University Hospital, Pakistan
| | | | | | | | - Anwar Ahmed
- Department of Radiology, Aga Khan University Hospital, Pakistan
| | - Ubaid Khan
- King Edward Medical University, Lahore, Pakistan
| | | |
Collapse
|
30
|
Retinal microvasculature is a potential biomarker for acute mountain sickness. SCIENCE CHINA. LIFE SCIENCES 2023:10.1007/s11427-022-2271-x. [PMID: 36811802 DOI: 10.1007/s11427-022-2271-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Academic Contribution Register] [Received: 09/09/2022] [Accepted: 12/21/2022] [Indexed: 02/24/2023]
Abstract
Increased cerebral blood flow resulting from altered capillary level autoregulation at high altitudes leads to capillary overperfusion and then vasogenic cerebral edema, which is the leading hypothesis of acute mountain sickness (AMS). However, studies on cerebral blood flow in AMS have been mostly restricted to gross cerebrovascular endpoints as opposed to the microvasculature. This study aimed to investigate ocular microcirculation alterations, the only visualized capillaries in the central neural system (CNS), during early-stage AMS using a hypobaric chamber. This study found that after high altitude simulation, the optic nerve showed retinal nerve fiber layer thickening (P=0.004-0.018) in some locations, and the area of the optic nerve subarachnoid space (P=0.004) enlarged. Optical coherence tomography angiography (OCTA) showed increased retinal radial peripapillary capillary (RPC) flow density (P=0.003-0.046), particularly on the nasal side of the nerve. The AMS-positive group had the largest increases in RPC flow density in the nasal sector (AMS-positive, Δ3.21±2.37; AMS-negative, Δ0.01±2.16, P=0.004). Among multiple ocular changes, OCTA increase in RPC flow density was associated with simulated early-stage AMS symptoms (beta=0.222, 95%CI, 0.009-0.435, P=0.042). The area under the receiver operating characteristics curve (AUC) for the changes in RPC flow density to predict early-stage AMS outcomes was 0.882 (95%CI, 0.746-0.998). The results further confirmed that overperfusion of microvascular beds is the key pathophysiologic change in early-stage AMS. RPC OCTA endpoints may serve as a rapid, noninvasive potential biomarker for CNS microvascular changes and AMS development during risk assessment of individuals at high altitudes.
Collapse
|
31
|
Zhang J, Tang S, Chen C, Jiang H, Liao H, Liu H, Wang L, Chen X. A bibliometric analysis of the studies in high-altitude induced sleep disturbances and cognitive impairment research. Front Physiol 2023; 14:1133059. [PMID: 36860517 PMCID: PMC9968939 DOI: 10.3389/fphys.2023.1133059] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 12/28/2022] [Accepted: 01/26/2023] [Indexed: 02/16/2023] Open
Abstract
Background: The two main symptoms at high altitude, sleep abnormalities and cognitive impairments, interact with each other. These two dysfunctions are also closely related to systemic multisystem diseases, including cerebrovascular diseases, psychiatric disorders, and immune regulatory diseases. Purpose: To systematically analyze and visualize research on sleep disturbances and cognitive impairment at high altitudes using a bibliometrics method, and to determine future research directions by analyzing research trends and the latest hotspots. Methods: Publications from 1990 to 2022 on sleep disturbances and cognitive impairment at high altitudes were retrieved from the Web of Science. Using the R Bibliometrix software and Microsoft Excel, all data were examined statistically and qualitatively. For network visualization, the data were later exported into VOSviewer 1.6.17 and CiteSpace 6.1.R6. Results: A total of 487 articles in this area were published from 1990 to 2022. In this period, there was an overall increase in the number of publications. The United States has shown considerable importance in this sector. Bloch Konrad E was the most prolific and valuable author. The most prolific journal was High Altitude Medicine & Biology, and it has been the first choice for publishing in this field in recent years. Analysis of keyword co-occurrences suggested that research interest in the clinical manifestations of sleep disturbances and cognitive impairment caused by altitude hypoxia was mainly focused on "acute mountain-sickness," "insomnia," "apnea syndrome," "depression," "anxiety," "Cheyne-strokes respiration," and "pulmonary hypertension." The mechanisms of disease development related to "oxidative stress," "inflammation," "hippocampus," "prefrontal cortex," "neurodegeneration," and "spatial memory" in the brain have been the focus of recent research. According to burst detection analysis, "mood" and "memory impairment," as terms with high strength, are expected to remain hot topics in the coming years. High-altitude-induced pulmonary hypertension is also in the emerging stage of research, and the treatments will continue to receive attention in the future. Conclusion: More attention is being focused on sleep disturbances and cognitive impairment at high altitudes. This work will serve as a useful reference for the clinical development of treatments for sleep disturbances and cognitive impairment induced by hypobaric hypoxia at high altitudes.
Collapse
Affiliation(s)
- Jiexin Zhang
- Department of Laboratory Medicine, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China
| | - Songyuan Tang
- Faculty of Life Sciences and Engineering, Southwest Jiaotong University, Chengdu, Sichuan, China
| | - Chao Chen
- Department of Osteology, The 5th People’s Hospital of Jinan, Jinan, Shandong, China
| | - Hezhong Jiang
- Faculty of Life Sciences and Engineering, Southwest Jiaotong University, Chengdu, Sichuan, China
| | - Hai Liao
- Department of Laboratory Medicine, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China
| | - Huawei Liu
- Department of Laboratory Medicine, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China
| | - Li Wang
- Sichuan Baicheng Chinese Medicine Technology Co., Chengdu, Sichuan, China
| | - Xin Chen
- Department of Laboratory Medicine, The Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, China,*Correspondence: Xin Chen,
| |
Collapse
|
32
|
Zhao R, Xu Y, Wang X, Zhou X, Liu Y, Jiang S, Zhang L, Yu Z. Withaferin A Enhances Mitochondrial Biogenesis and BNIP3-Mediated Mitophagy to Promote Rapid Adaptation to Extreme Hypoxia. Cells 2022; 12:cells12010085. [PMID: 36611879 PMCID: PMC9818179 DOI: 10.3390/cells12010085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 11/01/2022] [Revised: 12/21/2022] [Accepted: 12/22/2022] [Indexed: 12/28/2022] Open
Abstract
Rapid adaptation to extreme hypoxia is a challenging problem, and there is no effective scheme to achieve rapid adaptation to extreme hypoxia. In this study, we found that withaferin A (WA) can significantly reduce myocardial damage, maintain cardiac function, and improve survival in rats in extremely hypoxic environments. Mechanistically, WA protects against extreme hypoxia by affecting BCL2-interacting protein 3 (BNIP3)-mediated mitophagy and the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)-mediated mitochondrial biogenesis pathway among mitochondrial quality control mechanisms. On the one hand, enhanced mitophagy eliminates hypoxia-damaged mitochondria and prevents the induction of apoptosis; on the other hand, enhanced mitochondrial biogenesis can supplement functional mitochondria and maintain mitochondrial respiration to ensure mitochondrial ATP production under acute extreme hypoxia. Our study shows that WA can be used as an effective drug to improve tolerance to extreme hypoxia.
Collapse
Affiliation(s)
- Ruzhou Zhao
- Department of Aerospace Physiology, Air Force Medical University, 169# Changle West Road, Xi’an 710032, China
- Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China
| | - Yixin Xu
- Beijing Institute of Biotechnology, Academy of Military Medical Sciences (AMMS), Beijing 100071, China
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China
| | - Xiaobo Wang
- Department of Aerospace Physiology, Air Force Medical University, 169# Changle West Road, Xi’an 710032, China
| | - Xiang Zhou
- Department of Aerospace Physiology, Air Force Medical University, 169# Changle West Road, Xi’an 710032, China
| | - Yanqi Liu
- Department of Aerospace Physiology, Air Force Medical University, 169# Changle West Road, Xi’an 710032, China
| | - Shuai Jiang
- Department of Aerospace Physiology, Air Force Medical University, 169# Changle West Road, Xi’an 710032, China
| | - Lin Zhang
- Department of Aerospace Physiology, Air Force Medical University, 169# Changle West Road, Xi’an 710032, China
| | - Zhibin Yu
- Department of Aerospace Physiology, Air Force Medical University, 169# Changle West Road, Xi’an 710032, China
- Correspondence:
| |
Collapse
|
33
|
Abstract
This study was conducted to investigate the effects of high-altitude hypoxic environments on the gut microbiota. Male Sprague-Dawley rats were randomly divided into three groups, namely, the plain, moderate-altitude hypoxic, and high-altitude hypoxic groups. On the 3rd, 7th, 15th, and 30th days of exposure, fecal samples were collected and analyzed via 16S rRNA gene sequencing technology. Fecal microbiota transplantation (FMT) experiments were also performed. The results showed significant differences between the gut microbiota structure and diversity of rats in the high-altitude hypoxic group and those of rats in the other groups. Further, compared with that of rats in the plain group, the gut microbiota of rats in the two hypoxic groups showed the most significant changes on day 7. Furthermore, the gut microbiota of the rats in the FMT groups exhibited changes and became increasingly similar to those of the rats in the hypoxic groups. We also identified the phylum Firmicutes, genus Akkermansia, and genus Lactobacillus as the core microbiota under hypoxic conditions. Phenotypic analysis indicated a decrease in the proportion of aerobic bacteria and an increase in that of anaerobic bacteria, possibly owing to the high-altitude hypoxic environment. Additionally, functional analysis showed significant differences between the different groups with respect to different metabolic pathways, including carbohydrate metabolism, energy metabolism, glycan biosynthesis, and metabolism. These findings indicated significant changes in gut microbiota structure and diversity under high-altitude hypoxia, establishing a foundation for further research on the pathogenesis and development of diseases, as well as drug metabolism, under high-altitude hypoxia. IMPORTANCE In this study, we investigated the effects of high-altitude hypoxic environments with low oxygen levels on the gut microbiota characteristics of rats. We observed that high-altitude hypoxia is an important environmental factor that can affect gut microbiota structure and diversity, thereby affecting homeostasis in the host intestinal environment. These findings provide a basis for further studies on disease initiation and development, as well as drug metabolism, in high-altitude hypoxic environments.
Collapse
|
34
|
Furian M, Tannheimer M, Burtscher M. Effects of Acute Exposure and Acclimatization to High-Altitude on Oxygen Saturation and Related Cardiorespiratory Fitness in Health and Disease. J Clin Med 2022; 11:6699. [PMID: 36431176 PMCID: PMC9697047 DOI: 10.3390/jcm11226699] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 10/29/2022] [Revised: 11/08/2022] [Accepted: 11/09/2022] [Indexed: 11/16/2022] Open
Abstract
Maximal values of aerobic power (VO2max) and peripheral oxygen saturation (SpO2max) decline in parallel with gain in altitude. Whereas this relationship has been well investigated when acutely exposed to high altitude, potential benefits of acclimatization on SpO2 and related VO2max in healthy and diseased individuals have been much less considered. Therefore, this narrative review was primarily aimed to identify relevant literature reporting altitude-dependent changes in determinants, in particular SpO2, of VO2max and effects of acclimatization in athletes, healthy non-athletes, and patients suffering from cardiovascular, respiratory and/or metabolic diseases. Moreover, focus was set on potential differences with regard to baseline exercise performance, age and sex. Main findings of this review emphasize the close association between individual SpO2 and VO2max, and demonstrate similar altitude effects (acute and during acclimatization) in healthy people and those suffering from cardiovascular and metabolic diseases. However, in patients with ventilatory constrains, i.e., chronic obstructive pulmonary disease, steep decline in SpO2 and V̇O2max and reduced potential to acclimatize stress the already low exercise performance. Finally, implications for prevention and therapy are briefly discussed.
Collapse
Affiliation(s)
- Michael Furian
- Pulmonary Division, University Hospital Zurich, 8092 Zurich, Switzerland
- Research Department, Swiss University of Traditional Chinese Medicine, 5330 Bad Zurzach, Switzerland
| | - Markus Tannheimer
- Department of Sport and Rehabilitation Medicine, University of Ulm, 89075 Ulm, Germany
| | - Martin Burtscher
- Department of Sport Science, University of Innsbruck, 6020 Innsbruck, Austria
| |
Collapse
|
35
|
Zou Y, Yuan Z, Sun Y, Zhai M, Tan Z, Guan R, Aschner M, Luo W, Zhang J. Resetting Proteostasis of CIRBP with ISRIB Suppresses Neural Stem Cell Apoptosis under Hypoxic Exposure. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:3627026. [PMID: 36211820 PMCID: PMC9546721 DOI: 10.1155/2022/3627026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Academic Contribution Register] [Received: 05/11/2022] [Accepted: 07/19/2022] [Indexed: 11/17/2022]
Abstract
Neurological disorders are often progressive and lead to disabilities with limited available therapies. Epidemiological evidence implicated that prolonged exposure to hypoxia leads to neurological damage and a plethora of complications. Neural stem cells (NSCs) are a promising tool for neurological damage therapy in terms of their unique properties. However, the literature on the outcome of NSCs exposed to severe hypoxia is scarce. In this study, we identified a responsive gene that reacts to multiple cellular stresses, marked cold-inducible RNA-binding protein (CIRBP), which could attenuate NSC apoptosis under hypoxic pressure. Interestingly, ISRIB, a small-molecule modulator of the PERK-ATF4 signaling pathway, could prevent the reduction and apoptosis of NSCs in two steps: enhancing the expression of CIRBP through the protein kinase R- (PKR-) like endoplasmic reticulum kinase (PERK) and activating transcription factor 4 (ATF4) axis. Taken together, CIRBP was found to be a critical factor that could protect NSCs against apoptosis induced by hypoxia, and ISRIB could be acted upstream of the axis and may be recruited as an open potential therapeutic strategy to prevent or treat hypoxia-induced brain hazards.
Collapse
Affiliation(s)
- Yuankang Zou
- Department of Occupational and Environmental Health, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, No. 169 Chang Le West Rd., Xi'an, Shaanxi 710032, China
| | - Ziyan Yuan
- Institute of Medical Information and Library, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100020, China
| | - Yafei Sun
- Department of Occupational and Environmental Health, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, No. 169 Chang Le West Rd., Xi'an, Shaanxi 710032, China
| | - Maodeng Zhai
- Department of Occupational and Environmental Health, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, No. 169 Chang Le West Rd., Xi'an, Shaanxi 710032, China
| | - Zhice Tan
- Department of Occupational and Environmental Health, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, No. 169 Chang Le West Rd., Xi'an, Shaanxi 710032, China
| | - Ruili Guan
- Department of Occupational and Environmental Health, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, No. 169 Chang Le West Rd., Xi'an, Shaanxi 710032, China
| | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Wenjing Luo
- Department of Occupational and Environmental Health, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, No. 169 Chang Le West Rd., Xi'an, Shaanxi 710032, China
| | - Jianbin Zhang
- Department of Occupational and Environmental Health, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, No. 169 Chang Le West Rd., Xi'an, Shaanxi 710032, China
| |
Collapse
|
36
|
Gonzalez DE, McAllister MJ, Waldman HS, Ferrando AA, Joyce J, Barringer ND, Dawes JJ, Kieffer AJ, Harvey T, Kerksick CM, Stout JR, Ziegenfuss TN, Zapp A, Tartar JL, Heileson JL, VanDusseldorp TA, Kalman DS, Campbell BI, Antonio J, Kreider RB. International society of sports nutrition position stand: tactical athlete nutrition. J Int Soc Sports Nutr 2022; 19:267-315. [PMID: 35813846 PMCID: PMC9261739 DOI: 10.1080/15502783.2022.2086017] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 05/26/2022] [Accepted: 06/01/2022] [Indexed: 10/26/2022] Open
Abstract
This position stand aims to provide an evidence-based summary of the energy and nutritional demands of tactical athletes to promote optimal health and performance while keeping in mind the unique challenges faced due to work schedules, job demands, and austere environments. After a critical analysis of the literature, the following nutritional guidelines represent the position of the International Society of Sports Nutrition (ISSN). General Recommendations Nutritional considerations should include the provision and timing of adequate calories, macronutrients, and fluid to meet daily needs as well as strategic nutritional supplementation to improve physical, cognitive, and occupational performance outcomes; reduce risk of injury, obesity, and cardiometabolic disease; reduce the potential for a fatal mistake; and promote occupational readiness. Military Recommendations Energy demands should be met by utilizing the Military Dietary Reference Intakes (MDRIs) established and codified in Army Regulation 40-25. Although research is somewhat limited, military personnel may also benefit from caffeine, creatine monohydrate, essential amino acids, protein, omega-3-fatty acids, beta-alanine, and L-tyrosine supplementation, especially during high-stress conditions. First Responder Recommendations Specific energy needs are unknown and may vary depending on occupation-specific tasks. It is likely the general caloric intake and macronutrient guidelines for recreational athletes or the Acceptable Macronutrient Distribution Ranges for the general healthy adult population may benefit first responders. Strategies such as implementing wellness policies, setting up supportive food environments, encouraging healthier food systems, and using community resources to offer evidence-based nutrition classes are inexpensive and potentially meaningful ways to improve physical activity and diet habits. The following provides a more detailed overview of the literature and recommendations for these populations.
Collapse
Affiliation(s)
- Drew E. Gonzalez
- Exercise & Sport Nutrition Laboratory, Human Clinical Research Facility, Department of Health & Kinesiology Texas A&M University, College Station, TX, USA
| | - Matthew J. McAllister
- Texas State University, Metabolic and Applied Physiology Laboratory, Department of Health & Human Performance, San Marcos, TX, USA
| | - Hunter S. Waldman
- University of North Alabama, Department of Kinesiology, Florence, AL, USA
| | - Arny A. Ferrando
- University of Arkansas for Medical Sciences, Department of Geriatrics, Little Rock, AR, USA
| | - Jill Joyce
- Oklahoma State University, Department of Nutritional Sciences, Stillwater, OK, USA
| | - Nicholas D. Barringer
- US. Army-Baylor Master’s Program in Nutrition, Department of Nutrition, San Antonio, TX, USA
| | - J. Jay Dawes
- Oklahoma State University, Department of Kinesiology, Applied Health, and Recreation, Stillwater, OK, USA
| | - Adam J. Kieffer
- Brooke Army Medical Center, Department of Nutritional Medicine, San Antonio, TX, USA
| | - Travis Harvey
- United States Special Operations Command, Preservation of the Force and Family, Tampa, FL, USA
| | - Chad M. Kerksick
- Lindenwood University, Exercise and Performance Nutrition Laboratory, College of Science, Technology, and Health, St. Charles, MO, USA
| | - Jeffrey R. Stout
- University of Central Florida, Institute of Exercise Physiology and Rehabilitation Sciences, School of Kinesiology and Physical Therapy, Orlando, FL, USA
| | | | | | - Jamie L. Tartar
- Nova Southeastern University, Department of Psychology and Neuroscience, Fort Lauderdale, FL, USA
| | - Jeffery L. Heileson
- Baylor University, Department of Health, Human Performance, and Recreation, Waco, TX, USA
| | | | - Douglas S. Kalman
- Dr. Kiran C Patel College of Osteopathic Medicine, Nova Southeastern University, Nutrition Department, Davie, FL, USA
| | - Bill I. Campbell
- University of South Florida, Performance & Physique Enhancement Laboratory, Exercise Science Program, Tampa, FL, USA
| | - Jose Antonio
- Fight Science Laboratory, Nova Southeastern University, Department of Health and Human Performance, Davie, FL, USA
| | - Richard B. Kreider
- Exercise & Sport Nutrition Laboratory, Human Clinical Research Facility, Department of Health & Kinesiology Texas A&M University, College Station, TX, USA
| |
Collapse
|
37
|
Alarcón RF, Huayanay R, Monge E. Poor Knowledge of Acute Mountain Sickness in Latin American Medical Students. Wilderness Environ Med 2022; 33:148-153. [PMID: 35361528 DOI: 10.1016/j.wem.2021.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 01/19/2021] [Revised: 12/07/2021] [Accepted: 12/21/2021] [Indexed: 11/25/2022]
Abstract
INTRODUCTION Acute altitude exposure is a common event in Latin America that can result in mild to severe altitude illness. Medical students from some Latin American countries receive little information on this topic. Our aim was to determine the knowledge and incidence of acute mountain sickness (AMS), as well as the methods used to prevent AMS among medical students attending the Pan-American Student Meeting in Cusco, Peru, a city at high altitude (3400 m). METHODS We conducted a cross-sectional study on medical students attending a conference. Participants completed a questionnaire on the day of registration that collected demographic data and investigated students' knowledge of AMS, its prophylaxis, and their personal experience of symptoms. RESULTS A total of 840 students attended the meeting. Two hundred eighty-eight returned surveys, 51 from high altitude locations. Respondent age was 23±3 y (mean±SD), and 72% were female. Thirty-two percent had basic knowledge about symptoms of AMS. Headache was recognized as a symptom by 79%. Knowledge of AMS prophylaxis was reported by 70%. Coca leaf products and dimenhydrinate were mentioned by 30 and 16%, respectively, whereas acetazolamide was recognized by only 10% of participants. AMS incidence was 42%. Prophylactic measures were adopted by 47% of the participants in our study. Thirty-six percent used dimenhydrinate and 27% used coca tea. Less than 1% used acetazolamide as recommended. CONCLUSIONS We found poor knowledge of AMS and effective prophylaxis among medical students from several South American countries traveling to 3400 m.
Collapse
Affiliation(s)
- Renzo F Alarcón
- Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Peru, Sociedad Cientifica de San Fernando, Lima, Peru
| | - Ronal Huayanay
- Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Peru, Sociedad Cientifica de San Fernando, Lima, Peru.
| | - Eduardo Monge
- Hospital Daniel Carrión. Callao, Perú, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Peru
| |
Collapse
|
38
|
Rodriguez Lima DR, Pinzón Rondón ÁM, Rubio Ramos C, Pinilla Rojas DI, Niño Orrego MJ, Díaz Quiroz MA, Molano-González N, Ceballos Quintero JE, Arroyo Santos AF, Ruiz Sternberg ÁM. Clinical characteristics and mortality associated with COVID-19 at high altitude: a cohort of 5161 patients in Bogotá, Colombia. Int J Emerg Med 2022; 15:22. [PMID: 35597911 PMCID: PMC9123834 DOI: 10.1186/s12245-022-00426-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 09/03/2021] [Accepted: 05/08/2022] [Indexed: 01/08/2023] Open
Abstract
Background There are few data on the clinical outcomes of patients with coronavirus disease 2019 (COVID-19) in cities over 1000 m above sea level (masl). Objectives To describe the clinical characteristics and mortality of patients with COVID-19 treated at a high complexity hospital in Bogotá, Colombia, at 2640 masl. Methods This was an observational study of a cohort including 5161 patients with confirmed COVID-19 infection from 19 March 2020 to 30 April 2021. Demographic data, laboratory values, comorbidities, oxygenation indices, and clinical outcomes were collected. Data were compared between survivors and nonsurvivors. An independent predictive model was performed for mortality and invasive mechanical ventilation (IMV) using classification and regression trees (CART). Results The median cohort age was 66 years (interquartile range (IQR) 53–77), with 1305 patients dying (25%) and 3856 surviving (75%). The intensive care unit (ICU) received 1223 patients (24%). Of 898 patients who received IMV, 613 (68%) of them perished. The ratio of partial pressure arterial oxygen (PaO2) to fraction inspired oxygen (FiO2), or the P/F ratio, upon ICU admission was 105 (IQR 77–146) and 137 (IQR 91–199) in the deceased and survivors, respectively. The CART model showed that the need for IMV, age greater than 79 years, ratio of oxygen saturation (SaO2) to FiO2, or the S/F ratio, less than 259, and lactate dehydrogenase (LDH) greater than 617 U/L at admission were associated with a greater probability of death. Conclusion Among more than 5000 patients with COVID-19 treated in our hospital, mortality at hospital discharge was 25%. Older age, low S/F ratio, and high LDH at admission were predictors of mortality.
Collapse
Affiliation(s)
- David Rene Rodriguez Lima
- Critical and Intensive Care Medicine, Hospital Universitario Mayor-Méderi, Bogotá, Colombia. .,Grupo de Investigación Clínica, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia.
| | - Ángela María Pinzón Rondón
- Grupo de Investigación Clínica, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia
| | - Cristhian Rubio Ramos
- Critical and Intensive Care Medicine, Hospital Universitario Mayor-Méderi, Bogotá, Colombia
| | | | - Maria José Niño Orrego
- Grupo de Investigación Clínica, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia
| | - Mateo Andrés Díaz Quiroz
- Grupo de Investigación Clínica, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia
| | - Nicolás Molano-González
- Grupo de Investigación Clínica, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia
| | | | | | - Ángela María Ruiz Sternberg
- Grupo de Investigación Clínica, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia
| |
Collapse
|
39
|
Jiang S, Fan F, Yang L, Chen K, Sun Z, Zhang Y, Cairang N, Wang X, Meng X. Salidroside attenuates high altitude hypobaric hypoxia-induced brain injury in mice via inhibiting NF-κB/NLRP3 pathway. Eur J Pharmacol 2022; 925:175015. [PMID: 35561751 DOI: 10.1016/j.ejphar.2022.175015] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 12/06/2021] [Revised: 04/21/2022] [Accepted: 05/04/2022] [Indexed: 12/18/2022]
Abstract
Salidroside (Sal), an active ingredient from Rhodiola crenulate, has been reported to exert neuroprotection in cerebral injury from hypobaric hypoxia (HH) at high altitude. However, it remains to be understood whether its protective effects are related to inflammation suppression. In the present work, we aimed to reveal the mechanism of Sal attenuating HH-induced brain injury in mice caused by an animal hypobaric and hypoxic chamber. Our results provided that Sal could attenuate HH-evoked pathological injury and oxidative stress response by decreasing the content of ROS and MDA, and elevating the activities of SOD and GSH-Px. Sal treatment could partly enhance the energy metabolism, evidenced by increasing the activities of Na+-K+-ATPase, Ca2+-Mg2+-ATPase, ATP, SDH, HK and PK, while decreasing the release of LDH and LD. Meanwhile, Sal administration reversed the degradation of tight junction proteins ZO-1, Occludin and Claudin-5. Further, the increased levels of TNF-α, IL-1β and IL-6 were confined with Sal administration under the HH condition. Importantly, Sal could downregulate the proteins expression of p-NF-κB-p65, NLRP3, cleaved-Caspase-1 and ASC. Sal also decreased the protein expression of iNOS and COX2 with the increased CD206 and Arg1 expression. Taken together, these data provided that the inhibited NF-κB/NLRP3 pathway by Sal could attenuate HH-induced cerebral oxidative stress injury, inflammatory responses and the blood brain barrier (BBB) damage, attributing to the improved energy metabolism and the microglial phenotype of anti-inflammatory M2. The findings suggested that Sal was expected to be a promising anti-inflammatory agent for high altitude HH-induced brain injury.
Collapse
Affiliation(s)
- Shengnan Jiang
- School of Pharmacy, and Research Institute of Integrated TCM & Western Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China
| | - Fangfang Fan
- School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China
| | - Lu Yang
- School of Pharmacy, and Research Institute of Integrated TCM & Western Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China
| | - Ke Chen
- School of Pharmacy, and Research Institute of Integrated TCM & Western Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China
| | - Zhihao Sun
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China
| | - Yi Zhang
- School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China; Ethnic Medicine Academic Heritage Innovation Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China
| | - Nanjia Cairang
- University of Tibetan Medicine, Lasa, Tibet, 850000, China.
| | - Xiaobo Wang
- School of Pharmacy, and Research Institute of Integrated TCM & Western Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China; State Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China.
| | - Xianli Meng
- School of Pharmacy, and Research Institute of Integrated TCM & Western Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China; State Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China.
| |
Collapse
|
40
|
Lu Y, Han F, Liu Q, Wang Z, Wang T, Yang Z. Evaluation of Potential for Nature-Based Recreation in the Qinghai-Tibet Plateau: A Spatial-Temporal Perspective. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:5753. [PMID: 35565148 PMCID: PMC9100343 DOI: 10.3390/ijerph19095753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Academic Contribution Register] [Received: 04/10/2022] [Revised: 05/06/2022] [Accepted: 05/07/2022] [Indexed: 11/23/2022]
Abstract
Nature-based recreation (NBR) is an important cultural ecosystem service providing human well-being from natural environments. As the most concentrated and high-quality wilderness in China, the Qinghai-Tibet Plateau (QTP) has unique advantages for NBR. In this study, we designed an integrated nature-based recreation potential index (INRPI) based on four aspects: nature-based recreation resources, landscape attractiveness, recreation comfort and opportunity, and recreation reception ability. A combination of the analytic hierarchy process (AHP) and entropy evaluation method was adopted to assess the NBR potential in the QTP from 2000 to 2020. The research shows that: (i) The INRPI for the QTP decreases gradually from southeast to northwest and increases slightly from 2000 to 2020. (ii) The INRPI displays a pronounced difference on either side of the Qilian-Gyirong line. The areas with very high and high potentials mainly distributed in the southeast of the line, while areas with very low and low potentials distributed in the northwest. (iii) The construction of protected areas effectively improves NBR potential. Areas of INRPI at diverse levels within protected areas obviously increased in 2020. (iv) Increasing altitude has a notable effect on INRPI, and 3000 m is a critical dividing line for the NBR in the QTP. These findings can contribute to decision-makers in guiding rational use and spatial planning of natural land and promoting sustainable recreational development.
Collapse
Affiliation(s)
- Yayan Lu
- State Key Laboratory of Desert and Oasis Ecology, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi 830011, China; (Y.L.); (F.H.); (T.W.)
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Fang Han
- State Key Laboratory of Desert and Oasis Ecology, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi 830011, China; (Y.L.); (F.H.); (T.W.)
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Qun Liu
- Fujian Provincial Key Laboratory for Subtropical Resources and Environment, Fujian Normal University, Fuzhou 350007, China;
| | - Zhaoguo Wang
- College of Economic and Management, Shenyang Agricultural University, Shenyang 110866, China;
| | - Tian Wang
- State Key Laboratory of Desert and Oasis Ecology, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi 830011, China; (Y.L.); (F.H.); (T.W.)
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Zhaoping Yang
- State Key Laboratory of Desert and Oasis Ecology, Xinjiang Institute of Ecology and Geography, Chinese Academy of Sciences, Urumqi 830011, China; (Y.L.); (F.H.); (T.W.)
- University of Chinese Academy of Sciences, Beijing 100049, China
| |
Collapse
|
41
|
Biological Effect of Quercetin in Repairing Brain Damage and Cerebral Changes in Rats: Molecular Docking and In Vivo Studies. BIOMED RESEARCH INTERNATIONAL 2022; 2022:8962149. [PMID: 35528172 PMCID: PMC9071882 DOI: 10.1155/2022/8962149] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Academic Contribution Register] [Received: 01/24/2022] [Revised: 03/14/2022] [Accepted: 03/31/2022] [Indexed: 02/06/2023]
Abstract
This study examined the protective effect of quercetin against high-altitude-induced brain damage in rats. A molecular docking study was performed to investigate the potential effect of quercetin in reducing brain damages through its ability to target the oxidative stress enzymes. Biomarker assessment screening assays were also performed then followed by in vivo studies. Three groups of rats were divided into the control group, an untreated animal model group with induced brain damage, and finally, the quercetin treated group that received quercetin dose equal to 20 mg/kg of their body weights. Molecular docking studies and biomarker assessment screening assays proved the potential effect of quercetin to affect the level of representative biomarkers glutathione (GSH), glutathione reductase (GR), glutathione-S-transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA). Additionally, the protective effect of quercetin against high altitude, low pressure, and low oxygen was also investigated by exploring the brain histopathology of experimental rats. Brain damage was observed in the untreated animal model group. After treatment with quercetin, the cerebral edema in the brain tissues was improved significantly, confirming the protective effects of quercetin. Therefore, quercetin can be used as a natural food additive to protect from the highaltitude-induced brain damage.
Collapse
|
42
|
Wang Y, Shi Y, Li W, Wang S, Zheng J, Xu G, Li G, Shen X, Yang J. Gut microbiota imbalance mediates intestinal barrier damage in high-altitude exposed mice. FEBS J 2022; 289:4850-4868. [PMID: 35188712 DOI: 10.1111/febs.16409] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 10/20/2021] [Revised: 01/14/2022] [Accepted: 02/18/2022] [Indexed: 12/14/2022]
Abstract
The environmental conditions in high-altitude areas can induce gastrointestinal disorders and changes in gut microbiota. The gut microbiota is closely related to a variety of gastrointestinal diseases, although the underlying pathogenic mechanisms are not well-identified. The present study aimed to investigate the regulatory effect of high altitude on intestinal dysfunction via gut microbiota disturbance. Forty C57BL/6J mice were divided into four groups: one plain control group (CON) and three high-altitude exposure groups (HAE) (altitude: 4000 m a.s.l.; oxygen content: 12.7%; 1-, 2- and 4-week exposure). Another set of 40 mice was divided into two CON and two HAE subgroups. Antibiotic cocktails were administered to one CON and HAE groups and autoclaved water was administered to the second CON and HAE groups for 4 weeks, respectively. In the fecal microbiota transplantation experiment, there were four transplantation groups, which received, respectively: phosphate-buffered saline for 2 weeks, feces from CON for 2 weeks, feces from HAE-4W for 2 weeks, and HAE-4W for 4 weeks. Hematoxylin and eosin staining, periodic acid-Schiff staining, a terminal deoxynucleotidyl transferase dUTP nick end labeling assay and a quantitative reverse transcriptase-polymerase chain reaction were applied to detect changes in intestinal cellular structure, morphology, apoptosis and intestinal inflammatory response. Fecal microbiota was analyzed using 16S rDNA amplicon sequencing. A high-altitude environment changed the ecological balance of gut microbiota in mice and caused damage to the intestinal structure and mucosal barrier. Interestingly, similar damage, which was inhibited by antibiotic cocktails at high altitude, was observed in mice transplanted with fecal microbiota from HAE. A high-altitude environment contributes to dyshomeostasis of gut microbiota, thereby impairing the intestinal mucosal barrier, eventually inducing and exacerbating intestinal damage.
Collapse
Affiliation(s)
- Yuhao Wang
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases & Digestive Diseases of Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Yi Shi
- Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an, China
| | - Wenhao Li
- Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an, China
| | - Shu Wang
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases & Digestive Diseases of Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Jiyang Zheng
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases & Digestive Diseases of Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Guanghui Xu
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases & Digestive Diseases of Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Guixiang Li
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases & Digestive Diseases of Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Xuefeng Shen
- Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an, China
| | - Jianjun Yang
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases & Digestive Diseases of Xijing Hospital, Fourth Military Medical University, Xi'an, China
| |
Collapse
|
43
|
Chen CY, Chou CC, Lin KX, Mündel T, Chen MT, Liao YH, Tsai SC. A Sports Nutrition Perspective on the Impacts of Hypoxic High-Intensity Interval Training (HIIT) on Appetite Regulatory Mechanisms: A Narrative Review of the Current Evidence. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19031736. [PMID: 35162760 PMCID: PMC8835478 DOI: 10.3390/ijerph19031736] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Academic Contribution Register] [Received: 12/20/2021] [Revised: 01/27/2022] [Accepted: 01/30/2022] [Indexed: 01/11/2023]
Abstract
High-intensity interval training (HIIT) and low-oxygen exposure may inhibit the secretion of appetite-stimulating hormones, suppress appetite, and inhibit dietary intake. Physiological changes affecting appetite are frequent and include appetite hormone (ghrelin, leptin, PYY, and GLP-1) effects and the subjective loss of appetite, resulting in nutritional deficiencies. This paper is a narrative review of the literature to verify the HIIT effect on appetite regulation mechanisms and discusses the possible relationship between appetite effects and the need for high-intensity exercise training in a hypoxic environment. We searched MEDLINE/PubMed and the Web of Science databases, as well as English articles (gray literature by Google Scholar for English articles) through Google Scholar, and the searched studies primarily focused on the acute effects of exercise and hypoxic environmental factors on appetite, related hormones, and energy intake. In a general normoxic environment, regular exercise habits may have accustomed the athlete to intense training and, therefore, no changes occurred in their subjective appetite, but there is a significant effect on the appetite hormones. The higher the exercise intensity and the longer the duration, the more likely exercise is to cause exercise-induced appetite loss and changes in appetite hormones. It has not been clear whether performing HIIT in a hypoxic environment may interfere with the exerciser’s diet or the nutritional supplement intake as it suppresses appetite, which, in turn, affects and interferes with the recovery efficiency after exercise. Although appetite-regulatory hormones, the subjective appetite, and energy intake may be affected by exercise, such as hypoxia or hypoxic exercise, we believe that energy intake should be the main observable indicator in future studies on environmental and exercise interventions.
Collapse
Affiliation(s)
- Chung-Yu Chen
- Department of Exercise and Health Sciences, University of Taipei, Taipei City 111, Taiwan;
| | - Chun-Chung Chou
- Physical Education Office, National Taipei University of Technology, Taipei City 106, Taiwan;
| | - Ke-Xun Lin
- Department of Exercise and Health Science, National Taipei University of Nursing and Health Sciences, Taipei City 112, Taiwan;
| | - Toby Mündel
- School of Sport, Exercise and Nutrition, Massey University, Palmerston North 4442, New Zealand;
| | - Mu-Tsung Chen
- Department of Food and Beverage Management, Shih Chien University, Taipei City 104, Taiwan;
| | - Yi-Hung Liao
- Department of Exercise and Health Science, National Taipei University of Nursing and Health Sciences, Taipei City 112, Taiwan;
- Correspondence: (Y.-H.L.); (S.-C.T.)
| | - Shiow-Chwen Tsai
- Institute of Sports Sciences, University of Taipei, Taipei City 111, Taiwan
- Correspondence: (Y.-H.L.); (S.-C.T.)
| |
Collapse
|
44
|
Duan Y, Bai X, Yang J, Zhou Y, Gu W, Liu G, Wang Q, Zhu J, La L, Li X. Exposure to High-Altitude Environment Is Associated with Drug Transporters Change: microRNA-873-5p-Mediated Alteration of Function and Expression Levels of Drug Transporters under Hypoxia. Drug Metab Dispos 2022; 50:174-186. [PMID: 34844996 DOI: 10.1124/dmd.121.000681] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 09/17/2021] [Accepted: 11/12/2021] [Indexed: 11/22/2022] Open
Abstract
Hypoxia is the main characteristic of a high-altitude environment, affecting drug metabolism. However, so far, the mechanism of microRNA (miRNA) involved in the regulation of drug metabolism and transporters under high-altitude hypoxia is still unclear. This study aims to investigate the functions and expression levels of multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein 2 (MRP2), breast cancer resistance protein (BCRP), peptide transport 1 (PEPT1), and organic anion-transporting polypeptides 2B1 (OATP2B1) in rats and colon cancer (Caco-2) cells after exposure to high-altitude hypoxia. The protein and mRNA expression of MDR1, MRP2, BCRP, PEPT1, and OATP2B1 were determined by Western blot and qPCR. The functions of MDR1, MRP2, BCRP, PEPT1, and OATP2B1 were evaluated by determining the effective intestinal permeability and absorption rate constants of their specific substrates in rats under high-altitude hypoxia, and uptake and transport studies were performed on Caco-2 cells. To screen the miRNA associated with hypoxia, Caco-2 cells were examined by high throughput sequencing. We observed that the miR-873-5p was significantly decreased under hypoxia and might target MDR1 and pregnane X receptor (PXR). To clarify whether miR-873-5p regulates MDR1 and PXR under hypoxia, Caco-2 cells were transfected with mimics or inhibitors of miR-873-5p and negative control (NC). The function and expression of drug transporters were found to be significantly increased in rats and Caco-2 cells under hypoxia. We found that miR-873-5p regulated MDR1 and PXR expression. Herein, it is shown that miRNA may affect the expression of drug transporter and nuclear receptor under hypoxia. SIGNIFICANCE STATEMENT: This study explores if alterations to the microRNAs (miRNAs), induced by high-altitude hypoxia, can be translated to altered drug transporters. Among miRNAs, which show a significant change in a hypoxic environment, miR-873-5p can act on the multidrug resistance protein 1 (MDR1) gene; however, there are multiple miRNAs that can act on the pregnane X receptor (PXR). This study speculates that the miRNA-PXR-drug transporter axis is important in the physiological disposition of drugs.
Collapse
Affiliation(s)
- Yabin Duan
- Department of Clinical Pharmacy, Qinghai University Affiliated Hospital, Xining, China (Y.D.); Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China (Y.D., X.B., J.Y., G.L., J.Z., L.L.); and State Key Laboratory of Plateau Ecology and Agriculture (X.L.), and Medical College (Y.Z., W.G., Q.W., X.L.), Qinghai University, Xining, China
| | - Xue Bai
- Department of Clinical Pharmacy, Qinghai University Affiliated Hospital, Xining, China (Y.D.); Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China (Y.D., X.B., J.Y., G.L., J.Z., L.L.); and State Key Laboratory of Plateau Ecology and Agriculture (X.L.), and Medical College (Y.Z., W.G., Q.W., X.L.), Qinghai University, Xining, China
| | - Jianxin Yang
- Department of Clinical Pharmacy, Qinghai University Affiliated Hospital, Xining, China (Y.D.); Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China (Y.D., X.B., J.Y., G.L., J.Z., L.L.); and State Key Laboratory of Plateau Ecology and Agriculture (X.L.), and Medical College (Y.Z., W.G., Q.W., X.L.), Qinghai University, Xining, China
| | - Yang Zhou
- Department of Clinical Pharmacy, Qinghai University Affiliated Hospital, Xining, China (Y.D.); Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China (Y.D., X.B., J.Y., G.L., J.Z., L.L.); and State Key Laboratory of Plateau Ecology and Agriculture (X.L.), and Medical College (Y.Z., W.G., Q.W., X.L.), Qinghai University, Xining, China
| | - Wenqi Gu
- Department of Clinical Pharmacy, Qinghai University Affiliated Hospital, Xining, China (Y.D.); Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China (Y.D., X.B., J.Y., G.L., J.Z., L.L.); and State Key Laboratory of Plateau Ecology and Agriculture (X.L.), and Medical College (Y.Z., W.G., Q.W., X.L.), Qinghai University, Xining, China
| | - Guiqin Liu
- Department of Clinical Pharmacy, Qinghai University Affiliated Hospital, Xining, China (Y.D.); Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China (Y.D., X.B., J.Y., G.L., J.Z., L.L.); and State Key Laboratory of Plateau Ecology and Agriculture (X.L.), and Medical College (Y.Z., W.G., Q.W., X.L.), Qinghai University, Xining, China
| | - Qian Wang
- Department of Clinical Pharmacy, Qinghai University Affiliated Hospital, Xining, China (Y.D.); Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China (Y.D., X.B., J.Y., G.L., J.Z., L.L.); and State Key Laboratory of Plateau Ecology and Agriculture (X.L.), and Medical College (Y.Z., W.G., Q.W., X.L.), Qinghai University, Xining, China
| | - Junbo Zhu
- Department of Clinical Pharmacy, Qinghai University Affiliated Hospital, Xining, China (Y.D.); Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China (Y.D., X.B., J.Y., G.L., J.Z., L.L.); and State Key Laboratory of Plateau Ecology and Agriculture (X.L.), and Medical College (Y.Z., W.G., Q.W., X.L.), Qinghai University, Xining, China
| | - Linli La
- Department of Clinical Pharmacy, Qinghai University Affiliated Hospital, Xining, China (Y.D.); Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China (Y.D., X.B., J.Y., G.L., J.Z., L.L.); and State Key Laboratory of Plateau Ecology and Agriculture (X.L.), and Medical College (Y.Z., W.G., Q.W., X.L.), Qinghai University, Xining, China
| | - Xiangyang Li
- Department of Clinical Pharmacy, Qinghai University Affiliated Hospital, Xining, China (Y.D.); Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, China (Y.D., X.B., J.Y., G.L., J.Z., L.L.); and State Key Laboratory of Plateau Ecology and Agriculture (X.L.), and Medical College (Y.Z., W.G., Q.W., X.L.), Qinghai University, Xining, China
| |
Collapse
|
45
|
Fan F, Xu N, Sun Y, Li X, Gao X, Yi X, Zhang Y, Meng X, Lin JM. Uncovering the Metabolic Mechanism of Salidroside Alleviating Microglial Hypoxia Inflammation Based on Microfluidic Chip-Mass Spectrometry. J Proteome Res 2021; 21:921-929. [PMID: 34851127 DOI: 10.1021/acs.jproteome.1c00647] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 01/23/2023]
Abstract
Microglia are the main immune cells in the brain playing a critical role in neuroinflammation, and numerous pieces of evidence have proved that energy metabolism is closely associated with inflammation in activated microglia. Salidroside (Sal) isolated from Tibetan medicine Rhodiola crenulate can inhibit microglial hypoxia inflammation (HI). However, whether the inhibition is due to the intervening energy metabolic process in microglia is not clear. In this work, the hypoxic microenvironment of BV2 microglial cells was simulated using deferoxamine (DFO) in vitro and the change of cell metabolites (lactate, succinate, malate, and fumarate) was real-time online investigated based on a cell microfluidic chip-mass spectrometry (CM-MS) system. Meanwhile, for confirming the metabolic mechanism of BV2 cells under hypoxia, the level of HI-related factors (LDH, ROS, HIF-1α, NF-κB p65, TNF-α, IL-1β, and IL-6) was detected by molecular biotechnology. Integration of the detected results revealed that DFO-induced BV2 cell HI was associated with the process of energy metabolism, in which cell energy metabolism changed from oxidative phosphorylation to glycolysis. Furthermore, administration of Sal treatment could effectively invert this change, and two metabolites of Sal were identified: tyrosol and 4-hydroxyphenylacetic acid. In general, we illustrated a new mechanism of Sal for reducing BV2 cell HI injury and presented a novel analysis strategy that opened a way for real-time online monitoring of the energy metabolic mechanism of the effect of drugs on cells and further provided a superior strategy to screen natural drug candidates for HI-related brain disease treatment.
Collapse
Affiliation(s)
- Fangfang Fan
- State Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.,School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.,Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China
| | - Ning Xu
- Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China.,Institute of Quality Standard and Testing Technology for Agro-Products, The Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Yucheng Sun
- Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China
| | - Xuanhao Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Xinchang Gao
- Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China
| | - Xizhen Yi
- Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China
| | - Yi Zhang
- School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Xianli Meng
- State Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.,School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Jin-Ming Lin
- Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China
| |
Collapse
|
46
|
Stone RM, Ainslie PN, Tremblay JC, Akins JD, MacLeod DB, Tymko MM, DeSouza CA, Bain AR. GLOBAL REACH 2018: intra-arterial vitamin C improves endothelial-dependent vasodilatory function in humans at high altitude. J Physiol 2021; 600:1373-1383. [PMID: 34743333 DOI: 10.1113/jp282281] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 08/19/2021] [Accepted: 10/11/2021] [Indexed: 12/20/2022] Open
Abstract
High altitude-induced hypoxaemia is often associated with peripheral vascular dysfunction. However, the basic mechanism(s) underlying high-altitude vascular impairments remains unclear. This study tested the hypothesis that oxidative stress contributes to the impairments in endothelial function during early acclimatization to high altitude. Ten young healthy lowlanders were tested at sea level (344 m) and following 4-6 days at high altitude (4300 m). Vascular endothelial function was determined using the isolated perfused forearm technique with forearm blood flow (FBF) measured by strain-gauge venous occlusion plethysmography. FBF was quantified in response to acetylcholine (ACh), sodium nitroprusside (SNP) and a co-infusion of ACh with the antioxidant vitamin C (ACh+VitC). The total FBF response to ACh (area under the curve) was ∼30% lower at high altitude than at sea level (P = 0.048). There was no difference in the response to SNP at high altitude (P = 0.860). At sea level, the co-infusion of ACh+VitC had no influence on the FBF dose response (P = 0.268); however, at high altitude ACh+VitC resulted in an average increase in the FBF dose response by ∼20% (P = 0.019). At high altitude, the decreased FBF response to ACh, and the increase in FBF in response to ACh+VitC, were associated with the magnitude of arterial hypoxaemia (R2 = 0.60, P = 0.008 and R2 = 0.63, P = 0.006, respectively). Collectively, these data support the hypothesis that impairments in vascular endothelial function at high altitude are in part attributable to oxidative stress, a consequence of the magnitude of hypoxaemia. These data extend our basic understanding of vascular (mal)adaptation to high-altitude sojourns, with important implications for understanding the aetiology of high altitude-related vascular dysfunction. KEY POINTS: Vascular dysfunction has been demonstrated in lowlanders at high altitude (>4000 m). However, the extent of impairment and the delineation of contributing mechanisms have remained unclear. Using the gold-standard isolated perfused forearm model, we determined the extent of vasodilatory dysfunction and oxidative stress as a contributing mechanism in healthy lowlanders before and 4-6 days after rapid ascent to 4300 m. The total forearm blood flow response to acetylcholine at high altitude was decreased by ∼30%. Co-infusion of acetylcholine with the antioxidant vitamin C partially restored the total forearm blood flow by ∼20%. The magnitude of forearm blood flow reduction, as well as the impact of oxidative stress, was positively associated with the individual severity of hypoxaemia. These data extend our basic understanding of vascular (mal)adaptation to high-altitude sojourns, with important implications for understanding the aetiology of high altitude-related changes in endothelial-mediated vasodilatory function.
Collapse
Affiliation(s)
- Rachel M Stone
- Faculty of Human Kinetics, University of Windsor, Ontario, Canada
| | - Philip N Ainslie
- Kelowna, Centre for Heart Lung and Vascular Health, University of British Columbia, Vancouver, Canada
| | - Joshua C Tremblay
- Kelowna, Centre for Heart Lung and Vascular Health, University of British Columbia, Vancouver, Canada
| | | | - David B MacLeod
- Duke University School of Medicine, Durham, North Carolina, USA
| | | | | | - Anthony R Bain
- Faculty of Human Kinetics, University of Windsor, Ontario, Canada
| |
Collapse
|
47
|
Zhao R, Zhao X, Wang X, Liu Y, Yang J, Jiang S, Zhou X, Jiao B, Zhang L, Liu Y, Yu Z. Fasting promotes acute hypoxic adaptation by suppressing mTOR-mediated pathways. Cell Death Dis 2021; 12:1045. [PMID: 34732698 PMCID: PMC8566556 DOI: 10.1038/s41419-021-04351-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 07/13/2021] [Revised: 10/18/2021] [Accepted: 10/20/2021] [Indexed: 11/09/2022]
Abstract
Rapid adaptation to a hypoxic environment is an unanswered question that we are committed to exploring. At present, there is no suitable strategy to achieve rapid hypoxic adaptation. Here, we demonstrate that fasting preconditioning for 72 h reduces tissue injuries and maintains cardiac function, consequently significantly improving the survival rates of rats under extreme hypoxia, and this strategy can be used for rapid hypoxic adaptation. Mechanistically, fasting reduces blood glucose and further suppresses tissue mTOR activity. On the one hand, fasting-induced mTOR inhibition reduces unnecessary ATP consumption and increases ATP reserves under acute hypoxia as a result of decreased protein synthesis and lipogenesis; on the other hand, fasting-induced mTOR inhibition improves mitochondrial oxygen utilization efficiency to ensure ATP production under acute hypoxia, which is due to the significant decrease in ROS generation induced by enhanced mitophagy. Our findings highlight the important role of mTOR in acute hypoxic adaptation, and targeted regulation of mTOR could be a new strategy to improve acute hypoxic tolerance in the body.
Collapse
Affiliation(s)
- Ruzhou Zhao
- Department of Aerospace Physiology, Air Force Medical University, Xi'an, China
| | - Xingcheng Zhao
- Department of Aerospace Physiology, Air Force Medical University, Xi'an, China
| | - Xiaobo Wang
- Department of Aerospace Physiology, Air Force Medical University, Xi'an, China
| | - Yanqi Liu
- Department of Aerospace Physiology, Air Force Medical University, Xi'an, China
| | - Jie Yang
- Department of Aerospace Physiology, Air Force Medical University, Xi'an, China
| | - Shuai Jiang
- Department of Aerospace Physiology, Air Force Medical University, Xi'an, China
| | - Xiang Zhou
- Department of Aerospace Physiology, Air Force Medical University, Xi'an, China
- Department of Nuclear Medicine, Xijing Hospital, Air Force Medical University, Xi'an, China
| | - Bo Jiao
- Department of Aerospace Physiology, Air Force Medical University, Xi'an, China
| | - Lin Zhang
- Department of Aerospace Physiology, Air Force Medical University, Xi'an, China
| | - Yong Liu
- Department of Aerospace Physiology, Air Force Medical University, Xi'an, China.
| | - Zhibin Yu
- Department of Aerospace Physiology, Air Force Medical University, Xi'an, China.
| |
Collapse
|
48
|
Hypoxic Exercise Exacerbates Hypoxemia and Acute Mountain Sickness in Obesity: A Case Analysis. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18179078. [PMID: 34501667 PMCID: PMC8430682 DOI: 10.3390/ijerph18179078] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Academic Contribution Register] [Received: 07/11/2021] [Revised: 08/14/2021] [Accepted: 08/23/2021] [Indexed: 12/21/2022]
Abstract
Acute mountain sickness (AMS) is a common syndrome characterized by headache, dizziness, loss of appetite, weakness, and nausea. As a major public health issue, obesity has increased in high altitude urban residents and intermittent commuters to high altitudes. The present study investigated acute hypoxic exposure and hypoxic exercise on hypoxemia severity and AMS symptoms in a physically active obese man. In this case analysis, peripheral oxygen saturation (SpO2) was used to evaluate hypoxemia, heart rate (HR) and blood pressure (BP) were used to reflect the function of autonomic nervous system (ANS), and Lake Louise scoring (LLS) was used to assess AMS. The results showed that acute hypoxic exposure led to severe hypoxemia (SpO2 = 72%) and tachycardia (HRrest = 97 bpm), and acute hypoxic exercise exacerbated severe hypoxemia (SpO2 = 59%) and ANS dysfunction (HRpeak = 167 bpm, SBP/DBP = 210/97 mmHg). At the end of the 6-h acute hypoxic exposure, the case developed severe AMS (LLS = 10) symptoms of headache, gastrointestinal distress, cyanosis, vomiting, poor appetite, and fatigue. The findings of the case study suggest that high physical activity level appears did not show a reliable protective effect against severe hypoxemia, ANS dysfunction, and severe AMS symptoms in acute hypoxia exposure and hypoxia exercise.
Collapse
|
49
|
Nijiati Y, Yang T, Aimaiti M, Maimaitiyiming D, Aikemu A. Irbesartan ameliorates chronic mountain sickness in a rat model via the cholesterol metabolism: An iTRAQ -based proteomics analysis. Biomed Pharmacother 2021; 141:111802. [PMID: 34147903 DOI: 10.1016/j.biopha.2021.111802] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 03/24/2021] [Revised: 05/31/2021] [Accepted: 06/07/2021] [Indexed: 12/26/2022] Open
Abstract
OBJECTIVE To study the effects of irbesartan on pulmonary artery lesions in a rat model with chronic mountain sickness (CMS) and identify the biomarkers involved. METHODS In this study, we used a rat model of CMS to evaluate the therapeutic effect of irbesartan by measuring pulmonary artery pressure and evaluating the histopathology of the pulmonary artery. We also used proteomics technology to identify differentially expressed proteins (DEPs) in the serum and performed bioinformatics analysis. Results were then verified by enzyme linked immunosorbent assay (ELISA) and immunohistochemistry (IHC). RESULTS Irbesartan treatment induced a significant decrease (P < 0.05) in the pulmonary artery pressure of CMS rats. Histopathological and electron microscope further confirmed that high altitude hypoxia induced changes in the structure of the pulmonary artery tissue and caused ultrastructural lesions. Proteomics analysis identified 40 DEPs; bioinformatics analysis further revealed that the cholesterol metabolism pathway plays a crucial role in the occurrence of CMS. ELISA and IHC verified that several DEPs (Apo-A1, Apo-C1, Apo-E, IGF-1, Profilin1, and Col1a1) represent critical biological markers in pulmonary artery disease caused by CMS. CONCLUSIONS Irbesartan significantly improved pulmonary artery damage in a rat model of CMS possibly by impacting on the cholesterol metabolism pathway and by reducing damage to vascular endothelial cells. Irbesartan also inhibited the expression levels of IGF-1, Profilin1 and Col1a1 to relieve pulmonary artery pressure and improve lung function by inhibiting vascular remodeling. Several proteins were identified as potential biomarkers of CMS, including Apo-A1, Apo-C1, Apo-E, IGF-1, Profilin1, and Col1a1.
Collapse
Affiliation(s)
- Yiliyaer Nijiati
- Department of Drug Analysis, College of Pharmacy, Xinjiang Medical University, Urumqi 830017, Xinjiang, China; Central Laboratory of Xinjiang Medical University, Urumqi 830011, Xinjiang, China
| | - Tao Yang
- Central Laboratory of Xinjiang Medical University, Urumqi 830011, Xinjiang, China
| | - Mutalifu Aimaiti
- Central Laboratory of Xinjiang Medical University, Urumqi 830011, Xinjiang, China
| | - Dilinuer Maimaitiyiming
- Heart Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang, China
| | - Ainiwaer Aikemu
- Department of Drug Analysis, College of Pharmacy, Xinjiang Medical University, Urumqi 830017, Xinjiang, China; Key Laboratory of Active Components of Xinjiang Natural Medicine and Drug Release Technology, Xinjiang Medical University, Urumqi 830017, China.
| |
Collapse
|
50
|
Mallet RT, Burtscher J, Richalet JP, Millet GP, Burtscher M. Impact of High Altitude on Cardiovascular Health: Current Perspectives. Vasc Health Risk Manag 2021; 17:317-335. [PMID: 34135590 PMCID: PMC8197622 DOI: 10.2147/vhrm.s294121] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 04/14/2021] [Accepted: 05/12/2021] [Indexed: 12/12/2022] Open
Abstract
Globally, about 400 million people reside at terrestrial altitudes above 1500 m, and more than 100 million lowlanders visit mountainous areas above 2500 m annually. The interactions between the low barometric pressure and partial pressure of O2, climate, individual genetic, lifestyle and socio-economic factors, as well as adaptation and acclimatization processes at high elevations are extremely complex. It is challenging to decipher the effects of these myriad factors on the cardiovascular health in high altitude residents, and even more so in those ascending to high altitudes with or without preexisting diseases. This review aims to interpret epidemiological observations in high-altitude populations; present and discuss cardiovascular responses to acute and subacute high-altitude exposure in general and more specifically in people with preexisting cardiovascular diseases; the relations between cardiovascular pathologies and neurodegenerative diseases at altitude; the effects of high-altitude exercise; and the putative cardioprotective mechanisms of hypobaric hypoxia.
Collapse
Affiliation(s)
- Robert T Mallet
- Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX, USA
| | - Johannes Burtscher
- Department of Biomedical Sciences, University of Lausanne, Lausanne, CH-1015, Switzerland
- Institute of Sport Sciences, University of Lausanne, Lausanne, CH-1015, Switzerland
| | - Jean-Paul Richalet
- Laboratoire Hypoxie & Poumon, UMR Inserm U1272, Université Sorbonne Paris Nord 13, Bobigny Cedex, F-93017, France
| | - Gregoire P Millet
- Department of Biomedical Sciences, University of Lausanne, Lausanne, CH-1015, Switzerland
- Institute of Sport Sciences, University of Lausanne, Lausanne, CH-1015, Switzerland
| | - Martin Burtscher
- Department of Sport Science, University of Innsbruck, Innsbruck, A-6020, Austria
- Austrian Society for Alpine and High-Altitude Medicine, Mieming, Austria
| |
Collapse
|