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Wagner MS, Kranz M, Krenkel L, Pointner D, Foltan M, Lubnow M, Lehle K. Computer based visualization of clot structures in extracorporeal membrane oxygenation and histological clot investigations for understanding thrombosis in membrane lungs. Front Med (Lausanne) 2024; 11:1416319. [PMID: 38962744 PMCID: PMC11219572 DOI: 10.3389/fmed.2024.1416319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 06/06/2024] [Indexed: 07/05/2024] Open
Abstract
Extracorporeal membrane oxygenation (ECMO) was established as a treatment for severe cardiac or respiratory disease. Intra-device clot formation is a common risk. This is based on complex coagulation phenomena which are not yet sufficiently understood. The objective was the development and validation of a methodology to capture the key properties of clots deposed in membrane lungs (MLs), such as clot size, distribution, burden, and composition. One end-of-therapy PLS ML was examined. Clot detection was performed using multidetector computed tomography (MDCT), microcomputed tomography (μCT), and photography of fiber mats (fiber mat imaging, FMI). Histological staining was conducted for von Willebrand factor (vWF), platelets (CD42b, CD62P), fibrin, and nucleated cells (4', 6-diamidino-2-phenylindole, DAPI). The three imaging methods showed similar clot distribution inside the ML. Independent of the imaging method, clot loading was detected predominantly in the inlet chamber of the ML. The μCT had the highest accuracy. However, it was more expensive and time consuming than MDCT or FMI. The MDCT detected the clots with low scanning time. Due to its lower resolution, it only showed clotted areas but not the exact shape of clot structures. FMI represented the simplest variant, requiring little effort and resources. FMI allowed clot localization and calculation of clot volume. Histological evaluation indicated omnipresent immunological deposits throughout the ML. Visually clot-free areas were covered with leukocytes and platelets forming platelet-leukocyte aggregates (PLAs). Cells were embedded in vWF cobwebs, while vWF fibers were negligible. In conclusion, the presented methodology allowed adequate clot identification and histological classification of possible thrombosis markers such as PLAs.
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Affiliation(s)
- Maria S. Wagner
- Department of Cardiothoracic Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Michael Kranz
- Department of Biofluid Mechanics, Faculty of Mechanical Engineering, Technical University of Applied Sciences (OTH) Regensburg, Regensburg, Germany
- Regensburg Center of Biomedical Engineering, Facility of University Regensburg and Technical University of Applied Sciences (OTH) Regensburg, Regensburg, Germany
| | - Lars Krenkel
- Department of Biofluid Mechanics, Faculty of Mechanical Engineering, Technical University of Applied Sciences (OTH) Regensburg, Regensburg, Germany
- Regensburg Center of Biomedical Engineering, Facility of University Regensburg and Technical University of Applied Sciences (OTH) Regensburg, Regensburg, Germany
| | - Daniel Pointner
- Department of Biofluid Mechanics, Faculty of Mechanical Engineering, Technical University of Applied Sciences (OTH) Regensburg, Regensburg, Germany
- Regensburg Center of Biomedical Engineering, Facility of University Regensburg and Technical University of Applied Sciences (OTH) Regensburg, Regensburg, Germany
| | - Maik Foltan
- Department of Cardiothoracic Surgery, University Hospital Regensburg, Regensburg, Germany
| | - Matthias Lubnow
- Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany
| | - Karla Lehle
- Department of Cardiothoracic Surgery, University Hospital Regensburg, Regensburg, Germany
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Ticagrelor versus clopidogrel in reducing inflammatory cell infiltration of thrombus aspirated in patients with ST-elevation myocardial infarction. Eur J Clin Pharmacol 2022; 78:1391-1398. [PMID: 35674835 DOI: 10.1007/s00228-022-03348-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Accepted: 05/27/2022] [Indexed: 11/03/2022]
Abstract
BACKGROUND Ticagrelor provides more rapid, potent, and consistent anti-platelet efficacy than clopidogrel. This randomized trial aimed to evaluate the anti-inflammation effects of ticagrelor versus clopidogrel on thrombus aspirated from the ST-elevation myocardial infarction (STEMI) patients. METHOD A total of 98 patients with STEMI and intended percutaneous coronary intervention (PCI) were randomly assigned to receive clopidogrel (600-mg loading dose) or ticagrelor (180-mg loading dose), of whom 55 with large thrombus burden underwent thrombus aspiration during PCI. Thrombus specimens were successfully aspirated from 49 patients. Finally, 24 patients in the clopidogrel group and 23 in the ticagrelor group completed the study. Inflammatory cells within thrombi were assessed by hematoxylin-eosin and immunohistochemistry stainings. RESULTS Compared with the clopidogrel group, the number of total inflammatory cells per mm2 thrombus area in the ticagrelor group was decreased by 28% (P = 0.009). The numbers of neutrophils and myeloperoxidase-positive cells per mm2 thrombus area in the ticagrelor group were respectively decreased by 35% (P = 0.016) and 28% (P = 0.047), as compared with those in the clopidogrel group. Moreover, ticagrelor treatment reduced the ratio of monocytes number higher than 250 per mm2 thrombus area compared with clopidogrel treatment (4% versus 29%, P = 0.048). CONCLUSION In patients with undergoing PCI for STEMI, the loading dose ticagrelor regimen was associated with a reduction in inflammatory cell infiltration within thrombus compared with the loading dose clopidogrel regimen.
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Ribeiro DRP, Schmidt MM, Leguisamo N, Cambruzzi E, De Luca G, de Quadros AS. Immunohistochemical characteristics of coronary thrombi in ST-elevation myocardial infarction. AMERICAN HEART JOURNAL PLUS : CARDIOLOGY RESEARCH AND PRACTICE 2022; 18:100175. [PMID: 38559422 PMCID: PMC10978369 DOI: 10.1016/j.ahjo.2022.100175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 06/13/2022] [Accepted: 07/07/2022] [Indexed: 04/04/2024]
Abstract
Background and aims The dynamics and implications of intracoronary thrombus constituency in patients with ST-segment elevation myocardial infarction (STEMI) are not fully understood. We evaluated the expression of CD34, CD61and factor VIII surface markers in thrombi of patients with STEMI and its association with clinical and angiographic characteristics and major adverse cardiovascular events (MACE). Methods Patients presenting with STEMI undergoing aspiration thrombectomy during primary percutaneous coronary intervention (pPCI) were included. Morphological, histopathological and immunohistochemical aspects of thrombi were assessed by two pathologists blinded to clinical variables and outcomes. Results The mean age of the 245 patients included was 58 ± 12 years old, and 70 % were men. Regarding the thrombi microscopic patterns, 61 % were classified as recent, 20 % as lytic and 19 % as organized. There were higher levels of the CD61 index in patients with a history of heart failure. Smokers presented lower CD61 positive cells and CD61 index, but this association did not remain significant after multivariable analysis. There was an inverse correlation between CD61 positive cells and CD61 index with the time from onset of pain to the first medical contact, but no other significant association amongst clinical characteristics and antigenic expression. There was higher expression of the CD61 antigen in patients with in-hospital MACE, but statistical significance was borderline (p = 0.06). Conclusions In this cohort of patients with STEMI, immunohistochemistry of coronary thrombus showed a significantly higher platelet content in patients with previous heart failure and a trend in those with in-hospital MACE. Thrombus' platelet content was inversely related to ischemic time.
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Affiliation(s)
- Daniel Rios Pinto Ribeiro
- Instituto de Cardiologia do RS/Fundação Universitária de Cardiologia do Rio Grande do Sul – IC/FUC, Brazil
| | - Marcia Moura Schmidt
- Instituto de Cardiologia do RS/Fundação Universitária de Cardiologia do Rio Grande do Sul – IC/FUC, Brazil
| | - Natalia Leguisamo
- Instituto de Cardiologia do RS/Fundação Universitária de Cardiologia do Rio Grande do Sul – IC/FUC, Brazil
| | - Eduardo Cambruzzi
- Instituto de Cardiologia do RS/Fundação Universitária de Cardiologia do Rio Grande do Sul – IC/FUC, Brazil
| | - Giuseppe De Luca
- Division of Clinical and Experimental Cardiology AOU Sassari, University of Sassari, Italy
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Abstract
Despite effective therapeutic and preventive strategies, atherosclerosis and its complications still represent a substantial health burden. Leukocytes and inflammatory mechanisms are increasingly recognized as drivers of atherosclerosis. Neutrophil granulocytes within the circulation were recently shown to undergo neutrophil extracellular trap (NET) formation, linking innate immunity with acute complications of atherosclerosis. In this chapter, we summarize mechanisms of NET formation, evidence for their involvement in atherosclerosis and thrombosis, and potential therapeutic regimens specifically targeting NET components.
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Wadowski PP, Pultar J, Weikert C, Eichelberger B, Tscharre M, Koppensteiner R, Panzer S, Gremmel T. Platelet-to-Lymphocyte Ratio as Marker of Platelet Activation in Patients on Potent P2Y 12 Inhibitors. J Cardiovasc Pharmacol Ther 2022; 27:10742484221096524. [PMID: 35482903 DOI: 10.1177/10742484221096524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
A high platelet-to-lymphocyte ratio (PLR) has recently been associated with ischemic outcomes in cardiovascular disease. Increased platelet reactivity and leukocyte-platelet aggregate formation are directly involved in the progress of atherosclerosis and have been linked to ischemic events following percutaneous coronary intervention (PCI). In order to understand the relation of PLR with platelet reactivity, we assessed PLR as well as agonist-inducible platelet aggregation and neutrophil-platelet aggregate (NPA) formation in 182 acute coronary syndrome (ACS) patients on dual antiplatelet therapy with aspirin and prasugrel (n = 96) or ticagrelor (n = 86) 3 days after PCI. PLR was calculated from the blood count. Platelet aggregation was measured by multiple electrode aggregometry and NPA formation was determined by flow cytometry, both in response to ADP and SFLLRN. A PLR ≥91 was considered as high PLR based on previous data showing an association of this threshold with adverse ischemic outcomes. In the overall cohort and in prasugrel-treated patients, high PLR was associated with higher SFLLRN-inducible platelet aggregation (67 AU [50-85 AU] vs 59.5 AU [44.3-71.3 AU], P = .01, and 73 AU [50-85 AU] vs 61.5 AU [46-69 AU], P = .02, respectively). Further, prasugrel-treated patients with high PLR exhibited higher ADP- (15% [11%-23%] vs 10.9% [7.6%-15.9%], P = .007) and SFLLRN-inducible NPA formation (64.3% [55.4%-73.8%] vs 53.8% [44.1%-70.1%], P = .01) as compared to patients with low PLR. These differences were not seen in ticagrelor-treated patients. In conclusion, high PLR is associated with increased on-treatment platelet reactivity in prasugrel-treated patients, but not in patients on ticagrelor.
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Affiliation(s)
- Patricia P Wadowski
- Department of Internal Medicine II, 27271Medical University of Vienna, Vienna, Austria
| | - Joseph Pultar
- Department of Internal Medicine II, 27271Medical University of Vienna, Vienna, Austria
| | - Constantin Weikert
- Department of Internal Medicine II, 27271Medical University of Vienna, Vienna, Austria
| | - Beate Eichelberger
- Department of Blood Group Serology and Transfusion Medicine, 27271Medical University of Vienna, Vienna, Austria
| | - Maximilian Tscharre
- Department of Internal Medicine II, 27271Medical University of Vienna, Vienna, Austria.,Department of Internal Medicine, Cardiology and Nephrology, Landesklinikum Wiener Neustadt, Wiener Neustadt, Austria
| | - Renate Koppensteiner
- Department of Internal Medicine II, 27271Medical University of Vienna, Vienna, Austria
| | - Simon Panzer
- Department of Blood Group Serology and Transfusion Medicine, 27271Medical University of Vienna, Vienna, Austria
| | - Thomas Gremmel
- Department of Internal Medicine II, 27271Medical University of Vienna, Vienna, Austria.,Department of Internal Medicine I, Cardiology and Intensive Care Medicine, Landesklinikum Mistelbach-Gänserndorf, Mistelbach, Austria.,Institute of Antithrombotic Therapy in Cardiovascular Disease, Karl Landsteiner Society, St. Pölten, Austria
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Maniwa N, Fujino M, Nakai M, Nishimura K, Miyamoto Y, Kataoka Y, Asaumi Y, Tahara Y, Nakanishi M, Anzai T, Kusano K, Akasaka T, Goto Y, Noguchi T, Yasuda S. Anticoagulation combined with antiplatelet therapy in patients with left ventricular thrombus after first acute myocardial infarction. Eur Heart J 2019; 39:201-208. [PMID: 29029233 DOI: 10.1093/eurheartj/ehx551] [Citation(s) in RCA: 102] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Accepted: 09/07/2017] [Indexed: 01/08/2023] Open
Abstract
Aims There are limited data about the optimal anti-thrombotic therapy for preventing embolism while minimizing bleeding events in patients with first acute myocardial infarction (AMI) complicated by left ventricular thrombus (LVT). Methods and results Among 2301 consecutive patients with AMI hospitalized between 2001 and 2014, we studied 1850 patients with first AMI who discharged alive to investigate clinical characteristics, incidence of systemic embolism (SE), and association between anticoagulation and embolic or bleeding events. Left ventricular thrombus was diagnosed by echocardiography, left ventriculography, or cardiac magnetic resonance imaging in 92 (5.0%) patients (62 ± 12 years). During a median follow-up period of 5.4 years (interquartile range 2.1-9.1 years), SE occurred in 15 of 92 patients with LVT (16.3%) and 51 of 1758 patients without LVT (2.9%), respectively. Kaplan-Meier analysis showed a significantly higher incidence of SE in the LVT group (log-rank test, P < 0.001). Multivariate analysis showed that LVT was an independent predictor of SE. Among the LVT patients treated with vitamin K antagonists (n = 84), we compared the patients with therapeutic range (TTR) ≥50% (n = 34) and those with TTR <50% (n = 50). Only one embolic event developed in the TTR ≥50% group and nine embolic events developed in the TTR <50% group (2.9% vs. 19%, P = 0.036). There was no difference in major bleeding events (TTR ≥50%; 9% vs. TTR <50%; 8%, P = 0.89). Conclusion Appropriate anticoagulation therapy may decrease the incidence of embolic events without increasing the incidence of bleeding events in patients with first AMI complicated by LV thrombus.
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Affiliation(s)
- Naoki Maniwa
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan
| | - Masashi Fujino
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan
| | - Michikazu Nakai
- Department of Statistics and Data Analysis, Center for Cerebral and Cardiovascular Disease Information, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan
| | - Kunihiro Nishimura
- Department of Statistics and Data Analysis, Center for Cerebral and Cardiovascular Disease Information, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan
| | - Yoshihiro Miyamoto
- Department of Statistics and Data Analysis, Center for Cerebral and Cardiovascular Disease Information, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan
| | - Yu Kataoka
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan
| | - Yasuhide Asaumi
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan
| | - Yoshio Tahara
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan
| | - Michio Nakanishi
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan
| | - Toshihisa Anzai
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan
| | - Kengo Kusano
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan
| | - Takashi Akasaka
- Department of Cardiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8510, Japan
| | - Yoichi Goto
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan
| | - Teruo Noguchi
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan
| | - Satoshi Yasuda
- Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka 565-8565, Japan
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Sisakian HS, Mkhitaryan AG, Sahakyan VG, Kocharyan AS, Asatryan BA. [Morphological and Immunohystochemical Characteristics of Aspirated Thrombi in Patients with ST-Elevation Myocardial Infarction]. TERAPEVT ARKH 2019; 91:21-25. [PMID: 32598810 DOI: 10.26442/00403660.2019.09.000199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Indexed: 11/22/2022]
Abstract
The aim of study was to evaluate the morphological and immunohystochemical characteristics of aspirated thrombi in patients with ST-elevation myocardial infarction undergoing precutaneous coronary intervention to find the possible platelet activation and inflammatory cell involvement in coronary thrombi. MATERIALS AND METHODS Thrombi collected from 67 patients with ST-elevation myocardial infarction were studied. Macroscopic and immunohystochemical analyses were performed to reveal the cellular components of thrombi. The peroxidase - antiperoxidase immunohystochemical method was applied with monoclonal antibodies to CD4+, CD8+, CD15+, CD63+ and CD105+ using diaminobenzidine agent as a visualization agent to investigate the potential involvement of different cellular subpopulations. RESULTS The macroscopic examination revealed friable thrombi with apparent laminations (lines of Zahn). Microscopic analysis of thrombi revealed a loose meshwork of fibrin fibers with compact accumulation of activated platelets. The platelets were surrounded by neutrophilic granulocytes.The immunohystochemical analysis confirmed that cell aggregates are consisting of CD 63+ activated platelets and leucocytes. The granulocytes also tested positive for CD15 antigen. The immunohystochemical analysis revealed the presence of CD8+ cytotoxic T-lymphocytes and CD4+ helper T-lymphocytes. No expression of iNOS, CD105 and VEGF was found in the analyzed thrombi. CONCLUSIONS The hystopathological evaluation of thrombi in patients with acute ST-elevation myocardial infarction revealed the presence of activated CD63+ platelets and CD15+ neutrophilic granulocytes. Activated platelets and neutrophils may play a role in thromboinflammatory activation course leading to destabilization of atherosclerotic plaque and development of acute thrombosis in patients with ST-elevation acute myocardial infarction.
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Affiliation(s)
- H S Sisakian
- Yerevan State Medical University.,Clinic of General and Invasive Cardiology, University Hospital №1
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Cubedo J, Blasco A, Padró T, Ramaiola I, Juan-Babot O, Goicolea J, Fernández-Díaz J, Oteo J, Badimon L. Molecular signature of coronary stent thrombosis: oxidative stress and innate immunity cells. Thromb Haemost 2017. [DOI: 10.1160/th17-03-069] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
SummaryThe clinical impact of in-stent thrombosis is high because it is associated with high mortality and 20 % of the patients suffer a recurrent event within the two following years. The aim of this study was to characterise the morphologic and proteomic profile of in-stent thrombi (IST) in comparison to thrombi developed on native coronary arteries (CT) to identify a differential molecular signature. The study included 45 patients with ST-elevation-myocardial-infarction (STEMI) treated by primary-percutaneous-intervention and thrombus aspiration: 21 had IST and 24 had CT. Thrombi were characterised by morphologic immunohistochemical analysis and differential proteomic profiling (2-DE+MALDI-TOF/TOF). Bioinformatic analysis revealed differences in proteins related to oxidative-stress and cell death/survival. IST showed a higher content of structural proteins (gelsolin, actin-cytoplasmic-1, tropomyosin, and myosin) together with an imbalance in redox-homeostasis related proteins (increased superoxide-dismutase and decreased peroxiredoxin-2 thrombus content), and a coordinated increase of chaperones (HSP60 and HSC70) and cellular quality control-related proteins (26S–protease-regulatory-subunit-7). These changes were reflected into a significant decrease in HSC70 systemic levels and a significant increase in advanced-oxidation-protein-products (AOPP) indicative of increased oxidative stress-mediated protein damage in IST. Our results reveal an imbalance in redox-related proteins indicative of an exacerbated oxidative-stress that leads to an accumulation of AOPP serum levels in IST. Moreover, the coordinated increase in chaperones and regulatory proteins reflects the activation of intracellular protection mechanisms to maintain protein integrity in IST. The failure to counterbalance the stress situation could trigger cellular apoptosis leading to the destabilization of the thrombus and to a worse prognosis of IST-STEMI-patients.Supplementary Material to this article is available online at www.thrombosis-online.com.
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Parakh N, Utagi B, Arava S, Verma S, Karthikeyan G, Singh S, Bhargava B, Ray R, Patel CD, Bahl VK. Clinical significance of intracoronary thrombus aspirated during primary percutaneous intervention: An immunohistopathological study. CARDIOVASCULAR REVASCULARIZATION MEDICINE 2017; 19:241-246. [PMID: 29113867 DOI: 10.1016/j.carrev.2017.09.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Revised: 09/12/2017] [Accepted: 09/13/2017] [Indexed: 11/18/2022]
Abstract
BACKGROUND Manual thrombus aspiration during primary percutaneous intervention provides us with aspirated thrombus sample, that may contain material from the disrupted plaque. Immunohistopathological analysis of thrombus can yield valuable information about the clinical and cardiovascular outcomes and possible mechanisms of myocardial infarction. MATERIAL AND METHODS We studied and analysed the immunohistopathological features of coronary thrombus aspirated from patients undergoing primary percutaneous coronary angioplasty. Immunohistological staining included markers namely CD68, SMA and CD34 for macrophages, smooth muscle actin and endothelium, respectively. Major adverse cardiac events, angiographic outcome and infarct size were also noted. RESULTS Fifty-three patients (Mean age - 51.3±13years; males-47) who underwent primary percutaneous coronary intervention with aspiration thrombectomy were enrolled. Thrombus was successfully aspirated in 40 of 53 patients (75.4%). Patients with successful thrombus aspiration had higher ST-segment resolution (≥50%) as compared to patients with failed thrombus aspiration. Presence of RBC-rich thrombus on microscopy was more commonly associated with post-procedure TIMI flow of <2 as compared to patients with fibrin-rich thrombus and a trend towards lower myocardial blush grade<2 (P=0.10), and a significantly higher final infarct size (37.5±5% vs 25±15%; P=0.04 of myocardium) on nuclear scan. Immunohistology revealed presence of plaque material in 72% (26/36) of the samples. CONCLUSIONS Immunohistopathological evaluation of intracoronary thrombus may be of prognostic importance. High prevalence of plaque material in the aspirated intracoronary thrombus suggests plaque rupture as a possible etiology for vessel occlusion in these patients. SHORT SUMMARY Immunohistopathological evaluation of intracoronary thrombus reveals high prevalence of plaque material in the aspirated intracoronary thrombus suggesting plaque rupture as a possible etiology for vessel occlusion in Indian STEMI patients.
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Affiliation(s)
- Neeraj Parakh
- Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India.
| | - Basavaraj Utagi
- Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
| | - Sudhir Arava
- Department of Cardiac Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Sunil Verma
- Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
| | - Ganesan Karthikeyan
- Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
| | - Sandeep Singh
- Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
| | - Balram Bhargava
- Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
| | - Ruma Ray
- Department of Cardiac Pathology, All India Institute of Medical Sciences, New Delhi, India
| | - Chetan D Patel
- Department of Nuclear Cardiology, All India Institute of Medical Sciences, New Delhi, India
| | - Vinay K Bahl
- Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India
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Fuijkschot WW, Groothuizen WE, Appelman Y, Radonic T, van Royen N, van Leeuwen MA, Krijnen PA, van der Wal AC, Smulders YM, Niessen HW. Inflammatory cell content of coronary thrombi is dependent on thrombus age in patients with ST-elevation myocardial infarction. J Cardiol 2017; 69:394-400. [DOI: 10.1016/j.jjcc.2016.10.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Revised: 09/16/2016] [Accepted: 10/12/2016] [Indexed: 10/20/2022]
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Sheng F, Chen B, He M, Zhang M, Shen G. Neutrophil to Lymphocyte Ratio Is Related to Electrocardiographic Sign of Spontaneous Reperfusion in Patients with ST-segment Elevation Myocardial Infarction. Arch Med Res 2016; 47:180-5. [PMID: 27344371 DOI: 10.1016/j.arcmed.2016.06.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2015] [Accepted: 06/08/2016] [Indexed: 10/21/2022]
Abstract
BACKGROUND AND AIMS ST-segment resolution ≥70% on consecutive electrocardiograms (ECGs) before administration of definitive reperfusion therapy is considered as an electrocardiographic sign of spontaneous reperfusion (SR) in STEMI patients and it indicates not only the patency of the infarct-related artery (IRA) but also the microvascular and myocardial reperfusion. Neutrophil/lymphocyte (N/L) ratio has been demonstrated to be associated with the patency of the IRA and no-reflow in patients with STEMI before mechanical reperfusion therapy. However, the association between N/L ratio and ST-segment resolution in STEMI patients with SR was not investigated. The aim of this study was to focus on the relation between N/L ratio and ST-segment resolution in STEMI patients with SR. METHODS One hundred sixty two consecutive patients with their first diagnosed STEMI were enrolled in this study. ECGs of all the patients at admission and 1 h later were obtained. According to electrocardiographic sign of SR, the patients were divided into two groups as SR group and non-SR group. Clinical data between two groups were evaluated. RESULTS Patients in SR group had lower neutrophil counts, higher lymphocyte counts, and lower N/L ratio than patients in non-SR group. Moreover, after undertaking primary PCI, patients in SR group had lower peak cTnT value and higher LVEF than patients in non-SR group. Furthermore, N/L ratio was an independent predictor of electrocardiographic sign of SR in patients with STEMI. CONCLUSION N/L ratio, an easily available laboratory data, may be related to microvascular reperfusion in STEMI patients with electrocardiographic sign of SR.
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Affiliation(s)
- Fuqiang Sheng
- Department of Cardiology, Shanghai Songjiang District Central Hospital, Shanghai, China.
| | - Bin Chen
- Department of Cardiology, East Hospital, Affiliated Shanghai 6(th) Renmin Hospital, Shanghai, China
| | - Maorong He
- Department of Cardiology, Shanghai Songjiang District Central Hospital, Shanghai, China
| | - Meilin Zhang
- Department of Cardiology, Shanghai Songjiang District Central Hospital, Shanghai, China
| | - Guoying Shen
- Department of Cardiology, Shanghai Songjiang District Central Hospital, Shanghai, China
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The Role of Spleen-Derived Immune Cells in Ischemic Brain Injury. SPRINGER SERIES IN TRANSLATIONAL STROKE RESEARCH 2016. [DOI: 10.1007/978-3-319-32337-4_10] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Shibata T, Kawakami S, Noguchi T, Tanaka T, Asaumi Y, Kanaya T, Nagai T, Nakao K, Fujino M, Nagatsuka K, Ishibashi-Ueda H, Nishimura K, Miyamoto Y, Kusano K, Anzai T, Goto Y, Ogawa H, Yasuda S. Prevalence, Clinical Features, and Prognosis of Acute Myocardial Infarction Attributable to Coronary Artery Embolism. Circulation 2015. [PMID: 26216084 DOI: 10.1161/circulationaha.114.015134] [Citation(s) in RCA: 224] [Impact Index Per Article: 22.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Coronary artery embolism (CE) is recognized as an important nonatherosclerotic cause of acute myocardial infarction. Its prevalence, clinical features, and prognosis remain insufficiently characterized. METHODS AND RESULTS We screened 1776 consecutive patients who presented with de novo acute myocardial infarction between 2001 and 2013. CE was diagnosed based on criteria encompassing histological, angiographic, and other diagnostic imaging findings. The prevalence, clinical characteristics, treatment strategies, in-hospital outcomes, and long-term risk of CE recurrence or major adverse cardiac and cerebrovascular events (cardiac death, fatal arrhythmia, or recurrent thromboembolism) were evaluated. The prevalence of CE was 2.9% (n=52), including 8 (15%) patients with multivessel CE. Atrial fibrillation was the most common cause (n=38, 73%). Only 39% of patients with CE were treated with vitamin K antagonists, and the median international normalized ratio was 1.42 (range, 0.95-1.80). Eighteen of the 30 CE patients with nonvalvular atrial fibrillation had a CHADS2 score of 0 or 1. When those patients were reevaluated using CHA2DS2-VASc, 61% were reassigned to a higher risk category. During a median follow-up of 49 months, CE and thromboembolism recurred in 5 atrial fibrillation patients. The 5-year rate of major adverse cardiac and cerebrovascular events was 27.1%. In the propensity score-matched cohorts (n=45 each), Kaplan-Meier analysis showed a significantly higher incidence of cardiac death in the CE group than in the non-CE group (hazard ratio, 9.29; 95% confidence interval, 1.13-76.5; P<0.001). CONCLUSIONS Atrial fibrillation is the most frequent cause of CE. Patients with CE represent a high-risk subgroup of patients with acute myocardial infarction and require close follow-up.
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Affiliation(s)
- Tatsuhiro Shibata
- From Departments of Cardiovascular Medicine (T.S., S.K., T. Noguchi, Y.A., T.K., T. Nagai, K. Nakao, M.F., K.K., T.A., Y.G., H.O., S.Y.), Stroke and Cerebrovascular Disease (T.T., K. Nagatsuka), Pathology (H.I.-U.), and Preventive Medicine and Epidemiologic Informatics, Center for Cerebral and Cardiovascular Disease Information (K. Nishimura, Y.M.), National Cerebral and Cardiovascular Center, Suita, Japan
| | - Shoji Kawakami
- From Departments of Cardiovascular Medicine (T.S., S.K., T. Noguchi, Y.A., T.K., T. Nagai, K. Nakao, M.F., K.K., T.A., Y.G., H.O., S.Y.), Stroke and Cerebrovascular Disease (T.T., K. Nagatsuka), Pathology (H.I.-U.), and Preventive Medicine and Epidemiologic Informatics, Center for Cerebral and Cardiovascular Disease Information (K. Nishimura, Y.M.), National Cerebral and Cardiovascular Center, Suita, Japan
| | - Teruo Noguchi
- From Departments of Cardiovascular Medicine (T.S., S.K., T. Noguchi, Y.A., T.K., T. Nagai, K. Nakao, M.F., K.K., T.A., Y.G., H.O., S.Y.), Stroke and Cerebrovascular Disease (T.T., K. Nagatsuka), Pathology (H.I.-U.), and Preventive Medicine and Epidemiologic Informatics, Center for Cerebral and Cardiovascular Disease Information (K. Nishimura, Y.M.), National Cerebral and Cardiovascular Center, Suita, Japan.
| | - Tomotaka Tanaka
- From Departments of Cardiovascular Medicine (T.S., S.K., T. Noguchi, Y.A., T.K., T. Nagai, K. Nakao, M.F., K.K., T.A., Y.G., H.O., S.Y.), Stroke and Cerebrovascular Disease (T.T., K. Nagatsuka), Pathology (H.I.-U.), and Preventive Medicine and Epidemiologic Informatics, Center for Cerebral and Cardiovascular Disease Information (K. Nishimura, Y.M.), National Cerebral and Cardiovascular Center, Suita, Japan
| | - Yasuhide Asaumi
- From Departments of Cardiovascular Medicine (T.S., S.K., T. Noguchi, Y.A., T.K., T. Nagai, K. Nakao, M.F., K.K., T.A., Y.G., H.O., S.Y.), Stroke and Cerebrovascular Disease (T.T., K. Nagatsuka), Pathology (H.I.-U.), and Preventive Medicine and Epidemiologic Informatics, Center for Cerebral and Cardiovascular Disease Information (K. Nishimura, Y.M.), National Cerebral and Cardiovascular Center, Suita, Japan
| | - Tomoaki Kanaya
- From Departments of Cardiovascular Medicine (T.S., S.K., T. Noguchi, Y.A., T.K., T. Nagai, K. Nakao, M.F., K.K., T.A., Y.G., H.O., S.Y.), Stroke and Cerebrovascular Disease (T.T., K. Nagatsuka), Pathology (H.I.-U.), and Preventive Medicine and Epidemiologic Informatics, Center for Cerebral and Cardiovascular Disease Information (K. Nishimura, Y.M.), National Cerebral and Cardiovascular Center, Suita, Japan
| | - Toshiyuki Nagai
- From Departments of Cardiovascular Medicine (T.S., S.K., T. Noguchi, Y.A., T.K., T. Nagai, K. Nakao, M.F., K.K., T.A., Y.G., H.O., S.Y.), Stroke and Cerebrovascular Disease (T.T., K. Nagatsuka), Pathology (H.I.-U.), and Preventive Medicine and Epidemiologic Informatics, Center for Cerebral and Cardiovascular Disease Information (K. Nishimura, Y.M.), National Cerebral and Cardiovascular Center, Suita, Japan
| | - Kazuhiro Nakao
- From Departments of Cardiovascular Medicine (T.S., S.K., T. Noguchi, Y.A., T.K., T. Nagai, K. Nakao, M.F., K.K., T.A., Y.G., H.O., S.Y.), Stroke and Cerebrovascular Disease (T.T., K. Nagatsuka), Pathology (H.I.-U.), and Preventive Medicine and Epidemiologic Informatics, Center for Cerebral and Cardiovascular Disease Information (K. Nishimura, Y.M.), National Cerebral and Cardiovascular Center, Suita, Japan
| | - Masashi Fujino
- From Departments of Cardiovascular Medicine (T.S., S.K., T. Noguchi, Y.A., T.K., T. Nagai, K. Nakao, M.F., K.K., T.A., Y.G., H.O., S.Y.), Stroke and Cerebrovascular Disease (T.T., K. Nagatsuka), Pathology (H.I.-U.), and Preventive Medicine and Epidemiologic Informatics, Center for Cerebral and Cardiovascular Disease Information (K. Nishimura, Y.M.), National Cerebral and Cardiovascular Center, Suita, Japan
| | - Kazuyuki Nagatsuka
- From Departments of Cardiovascular Medicine (T.S., S.K., T. Noguchi, Y.A., T.K., T. Nagai, K. Nakao, M.F., K.K., T.A., Y.G., H.O., S.Y.), Stroke and Cerebrovascular Disease (T.T., K. Nagatsuka), Pathology (H.I.-U.), and Preventive Medicine and Epidemiologic Informatics, Center for Cerebral and Cardiovascular Disease Information (K. Nishimura, Y.M.), National Cerebral and Cardiovascular Center, Suita, Japan
| | - Hatsue Ishibashi-Ueda
- From Departments of Cardiovascular Medicine (T.S., S.K., T. Noguchi, Y.A., T.K., T. Nagai, K. Nakao, M.F., K.K., T.A., Y.G., H.O., S.Y.), Stroke and Cerebrovascular Disease (T.T., K. Nagatsuka), Pathology (H.I.-U.), and Preventive Medicine and Epidemiologic Informatics, Center for Cerebral and Cardiovascular Disease Information (K. Nishimura, Y.M.), National Cerebral and Cardiovascular Center, Suita, Japan
| | - Kunihiro Nishimura
- From Departments of Cardiovascular Medicine (T.S., S.K., T. Noguchi, Y.A., T.K., T. Nagai, K. Nakao, M.F., K.K., T.A., Y.G., H.O., S.Y.), Stroke and Cerebrovascular Disease (T.T., K. Nagatsuka), Pathology (H.I.-U.), and Preventive Medicine and Epidemiologic Informatics, Center for Cerebral and Cardiovascular Disease Information (K. Nishimura, Y.M.), National Cerebral and Cardiovascular Center, Suita, Japan
| | - Yoshihiro Miyamoto
- From Departments of Cardiovascular Medicine (T.S., S.K., T. Noguchi, Y.A., T.K., T. Nagai, K. Nakao, M.F., K.K., T.A., Y.G., H.O., S.Y.), Stroke and Cerebrovascular Disease (T.T., K. Nagatsuka), Pathology (H.I.-U.), and Preventive Medicine and Epidemiologic Informatics, Center for Cerebral and Cardiovascular Disease Information (K. Nishimura, Y.M.), National Cerebral and Cardiovascular Center, Suita, Japan
| | - Kengo Kusano
- From Departments of Cardiovascular Medicine (T.S., S.K., T. Noguchi, Y.A., T.K., T. Nagai, K. Nakao, M.F., K.K., T.A., Y.G., H.O., S.Y.), Stroke and Cerebrovascular Disease (T.T., K. Nagatsuka), Pathology (H.I.-U.), and Preventive Medicine and Epidemiologic Informatics, Center for Cerebral and Cardiovascular Disease Information (K. Nishimura, Y.M.), National Cerebral and Cardiovascular Center, Suita, Japan
| | - Toshihisa Anzai
- From Departments of Cardiovascular Medicine (T.S., S.K., T. Noguchi, Y.A., T.K., T. Nagai, K. Nakao, M.F., K.K., T.A., Y.G., H.O., S.Y.), Stroke and Cerebrovascular Disease (T.T., K. Nagatsuka), Pathology (H.I.-U.), and Preventive Medicine and Epidemiologic Informatics, Center for Cerebral and Cardiovascular Disease Information (K. Nishimura, Y.M.), National Cerebral and Cardiovascular Center, Suita, Japan
| | - Yoichi Goto
- From Departments of Cardiovascular Medicine (T.S., S.K., T. Noguchi, Y.A., T.K., T. Nagai, K. Nakao, M.F., K.K., T.A., Y.G., H.O., S.Y.), Stroke and Cerebrovascular Disease (T.T., K. Nagatsuka), Pathology (H.I.-U.), and Preventive Medicine and Epidemiologic Informatics, Center for Cerebral and Cardiovascular Disease Information (K. Nishimura, Y.M.), National Cerebral and Cardiovascular Center, Suita, Japan
| | - Hisao Ogawa
- From Departments of Cardiovascular Medicine (T.S., S.K., T. Noguchi, Y.A., T.K., T. Nagai, K. Nakao, M.F., K.K., T.A., Y.G., H.O., S.Y.), Stroke and Cerebrovascular Disease (T.T., K. Nagatsuka), Pathology (H.I.-U.), and Preventive Medicine and Epidemiologic Informatics, Center for Cerebral and Cardiovascular Disease Information (K. Nishimura, Y.M.), National Cerebral and Cardiovascular Center, Suita, Japan
| | - Satoshi Yasuda
- From Departments of Cardiovascular Medicine (T.S., S.K., T. Noguchi, Y.A., T.K., T. Nagai, K. Nakao, M.F., K.K., T.A., Y.G., H.O., S.Y.), Stroke and Cerebrovascular Disease (T.T., K. Nagatsuka), Pathology (H.I.-U.), and Preventive Medicine and Epidemiologic Informatics, Center for Cerebral and Cardiovascular Disease Information (K. Nishimura, Y.M.), National Cerebral and Cardiovascular Center, Suita, Japan
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Affiliation(s)
- Jean-Baptiste Michel
- From the UMR 1148, Inserm-Laboratory for Vascular Translation Science, Denis Diderot Université, Paris, France.
| | - Benoît Ho-Tin-Noé
- From the UMR 1148, Inserm-Laboratory for Vascular Translation Science, Denis Diderot Université, Paris, France
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Badimon L, Vilahur G. Neutrophil extracellular traps: a new source of tissue factor in atherothrombosis. Eur Heart J 2015; 36:1364-6. [PMID: 25845929 DOI: 10.1093/eurheartj/ehv105] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Affiliation(s)
- Lina Badimon
- Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain Cardiovascular Research Chair, UAB, Barcelona, Spain
| | - Gemma Vilahur
- Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain
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17
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Kupstyte N, Zaliunas R, Tatarunas V, Skipskis V, Zaliaduonyte-Peksiene D, Grabauskyte I, Dovidaitiene D, Bumblauskas K, Gustiene O, Lesauskaite V. Effect of clinical factors and gene polymorphism of CYP2C19*2, *17 and CYP4F2*3 on early stent thrombosis. Pharmacogenomics 2015; 16:181-9. [DOI: 10.2217/pgs.14.165] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Aim: To determine the main clinical and genetic factors having impact on early coronary stent thrombosis. Materials & methods: Genotyping of CYP2C19*2, *17 and CYP4F2*3 in patients with (n = 31) and without stent thrombosis (n = 456) was performed. Clinical and genetic data were analyzed by binary logistic regression. Results: Smoking (OR: 0.317; 95% CI: 0.131–0.767), high-density lipoprotein level in mmol/l (OR: 0.142; 95% CI: 0.040–0.506), CYP2C19*2*2 versus *1*1 and *1*2 genotype (OR: 11.625; 95% CI: 3.498–38.633), CYP4F2 AA versus GA and GG genotype (OR: 3.532; 95% CI: 1.153–10.822) were associated with early stent thrombosis. Conclusion: For the first time we have identified a clinically important polymorphism (CYP4F2 G1347A) that was independently associated with early stent thrombosis. Original submitted 18 August 2014; Revision submitted 10 November 2014
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Affiliation(s)
- Nora Kupstyte
- Institute of Cardiology of Lithuanian University of Health Sciences, Sukileliu 17, Kaunas, LT 50009, Lithuania
- Department of Cardiology of Lithuanian University of Health Sciences, Eiveniu 2, Kaunas, LT 50009, Lithuania
| | - Remigijus Zaliunas
- Department of Cardiology of Lithuanian University of Health Sciences, Eiveniu 2, Kaunas, LT 50009, Lithuania
| | - Vacis Tatarunas
- Institute of Cardiology of Lithuanian University of Health Sciences, Sukileliu 17, Kaunas, LT 50009, Lithuania
| | - Vilius Skipskis
- Institute of Cardiology of Lithuanian University of Health Sciences, Sukileliu 17, Kaunas, LT 50009, Lithuania
| | - Diana Zaliaduonyte-Peksiene
- Department of Cardiology of Lithuanian University of Health Sciences, Eiveniu 2, Kaunas, LT 50009, Lithuania
| | - Ingrida Grabauskyte
- Institute of Cardiology of Lithuanian University of Health Sciences, Sukileliu 17, Kaunas, LT 50009, Lithuania
| | - Dovile Dovidaitiene
- Department of Cardiology of Lithuanian University of Health Sciences, Eiveniu 2, Kaunas, LT 50009, Lithuania
| | - Karolis Bumblauskas
- Department of Cardiology of Lithuanian University of Health Sciences, Eiveniu 2, Kaunas, LT 50009, Lithuania
| | - Olivija Gustiene
- Department of Cardiology of Lithuanian University of Health Sciences, Eiveniu 2, Kaunas, LT 50009, Lithuania
| | - Vaiva Lesauskaite
- Institute of Cardiology of Lithuanian University of Health Sciences, Sukileliu 17, Kaunas, LT 50009, Lithuania
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18
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Helseth R, Seljeflot I, Opstad T, Solheim S, Freynhofer M, Arnesen H, Huber K, Weiss T. Genes expressed in coronary thrombi are associated with ischemic time in patients with acute myocardial infarction. Thromb Res 2015; 135:329-33. [DOI: 10.1016/j.thromres.2014.11.028] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2014] [Revised: 10/29/2014] [Accepted: 11/30/2014] [Indexed: 11/17/2022]
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19
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Maugeri N, Campana L, Gavina M, Covino C, De Metrio M, Panciroli C, Maiuri L, Maseri A, D'Angelo A, Bianchi ME, Rovere-Querini P, Manfredi AA. Activated platelets present high mobility group box 1 to neutrophils, inducing autophagy and promoting the extrusion of neutrophil extracellular traps. J Thromb Haemost 2014; 12:2074-88. [PMID: 25163512 DOI: 10.1111/jth.12710] [Citation(s) in RCA: 379] [Impact Index Per Article: 34.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2014] [Accepted: 08/08/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Increasing evidence implicates both platelets and neutrophils in the formation, stabilization, and growth of peripheral and coronary thrombi. Neutrophil extracellular traps (NETs) play a key role. The early events in the deregulated cross-talk between platelets and neutrophils are poorly characterized. OBJECTIVES To identify at the molecular level the mechanism through which platelets induce the generation of NETs in sterile conditions. PATIENTS/METHODS The presence of NETs was determined in 26 thrombi from patients with acute myocardial infarction by immunohistochemistry and immunofluorescence and markers of NETs assessed in the plasma. In vitro NET generation was studied in static and in physiological flow conditions. RESULTS Coronary thrombi mainly consist of activated platelets, neutrophils, and NETs in close proximity of platelets. Activated platelets commit neutrophils to NET generation. The event abates in the presence of competitive antagonists of the high mobility group box 1 (HMGB1) protein. Hmgb1(-/-) platelets fail to elicit NETs, whereas the HMGB1 alone commits neutrophils to NET generation. Integrity of the HMGB1 receptor, Receptor for Advanced Glycation End products (RAGE), is required for NET formation, as assessed using pharmacologic and genetic tools. Exposure to HMGB1 prevents depletion of mitochondrial potential, induces autophagosome formation, and prolongs neutrophil survival. These metabolic effects are caused by the activation of autophagy. Blockade of the autophagic flux reverts platelet HMGB1-elicited NET generation. CONCLUSIONS Activated platelets present HMGB1 to neutrophils and commit them to autophagy and NET generation. This chain of events may be responsible for some types of thromboinflammatory lesions and indicates novel paths for molecular intervention.
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Affiliation(s)
- N Maugeri
- Division of Regenerative Medicine, Gene Therapy and Stem Cells, Department of Medicine, San Raffaele Scientific Institute and Vita Salute San Raffaele University, Milan, Italy
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20
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Yalcinkaya E, Yuksel UC, Celik M, Kabul HK, Barcin C, Gokoglan Y, Yildirim E, Iyisoy A. Relationship between neutrophil-to-lymphocyte ratio and electrocardiographic ischemia grade in STEMI. Arq Bras Cardiol 2014; 104:112-9. [PMID: 25424159 PMCID: PMC4375654 DOI: 10.5935/abc.20140179] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2014] [Accepted: 08/25/2014] [Indexed: 11/21/2022] Open
Abstract
Background Neutrophil-to-lymphocyte ratio (NLR) has been found to be a good predictor of future
adverse cardiovascular outcomes in patients with ST-segment elevation myocardial
infarction (STEMI). Changes in the QRS terminal portion have also been associated with
adverse outcomes following STEMI. Objective To investigate the relationship between ECG ischemia grade and NLR in patients
presenting with STEMI, in order to determine additional conventional risk factors for
early risk stratification. Methods Patients with STEMI were investigated. The grade of ischemia was analyzed from the ECG
performed on admission. White blood cells and subtypes were measured as part of the
automated complete blood count (CBC) analysis. Patients were classified into two groups
according to the ischemia grade presented on the admission ECG, as grade 2 ischemia
(G2I) and grade 3 ischemia (G3I). Results Patients with G3I had significantly lower mean left ventricular ejection fraction than
those in G2I (44.58 ± 7.23 vs. 48.44 ± 7.61, p = 0.001). As expected, in-hospital
mortality rate increased proportionally with the increase in ischemia grade (p = 0.036).
There were significant differences in percentage of lymphocytes (p = 0.010) and
percentage of neutrophils (p = 0.004), and therefore, NLR was significantly different
between G2I and G3I patients (p < 0.001). Multivariate logistic regression analysis
revealed that only NLR was the independent variable with a significant effect on ECG
ischemia grade (odds ratio = 1.254, 95% confidence interval 1.120–1.403, p <
0.001). Conclusion We found an association between G3I and elevated NLR in patients with STEMI. We believe
that such an association might provide an additional prognostic value for risk
stratification in patients with STEMI when combined with standardized risk scores.
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Affiliation(s)
| | - Uygar Cagdas Yuksel
- Department of Cardiology, School of Medicine, Gulhane Military Medical Academy
| | - Murat Celik
- Department of Cardiology, School of Medicine, Gulhane Military Medical Academy
| | - Hasan Kutsi Kabul
- Department of Cardiology, School of Medicine, Gulhane Military Medical Academy
| | - Cem Barcin
- Department of Cardiology, School of Medicine, Gulhane Military Medical Academy
| | - Yalcin Gokoglan
- Department of Cardiology, School of Medicine, Gulhane Military Medical Academy
| | - Erkan Yildirim
- Department of Cardiology, School of Medicine, Gulhane Military Medical Academy
| | - Atila Iyisoy
- Department of Cardiology, School of Medicine, Gulhane Military Medical Academy
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Coronary thrombi neovascularization in patients with ST-elevation myocardial infarction - clinical and angiographic implications. Thromb Res 2014; 134:1038-45. [DOI: 10.1016/j.thromres.2014.09.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2014] [Revised: 08/14/2014] [Accepted: 09/09/2014] [Indexed: 11/23/2022]
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Abstract
BACKGROUND Spontaneous early patency of infarct-related artery (IRA) on arrival for primary percutaneous coronary intervention is associated with better short- and long-term prognosis in patients with ST-segment elevation myocardial infarction (STEMI). We aimed to investigate whether the hemographic parameters on admission are associated with spontaneous IRA patency. METHODS This was a retrospective study of 1,625 patients with acute STEMI who underwent primary percutaneous coronary intervention<12 hours after the onset of symptoms. RESULTS Angiography showed patent IRA (prethrombolysis in myocardial infarction [TIMI] grade 3 flow) in 160 (9.8%) patients. Neutrophil count on admission (7.8±2.4×10³/μL versus 9.7±3.8×10³/μL; P<0.001) was significantly lower and lymphocyte count (2.4±1.0×10³/μL versus 1.9±1.1×10³/μL; P<0.001) on admission was significantly higher in the patent IRA group. Neutrophil to lymphocyte ratio (NLR) was significantly lower in the patent IRA group (4.1±3.2 versus 6.9±5.5; P<0.001). Admission leukocyte counts (13±4.0×10³/μL versus 12±3.4×10³/μL; P<0.001) and NLR (7.2±5.8 versus 5.5±4.4; P<0.001) of the patients with TIMI thrombus score≥4 were significantly higher than patients with TIMI thrombus score<4. In the multivariate analysis, NLR≥4.5 (3.17 [95% confidence interval: 2.04-4.92]; P<0.001) was found to be independently predicting an occluded IRA on initial angiography with a sensitivity of 62.7% and a specificity of 70%. CONCLUSIONS NLR on admission is significantly related to angiographic thrombus burden and spontaneous early IRA patency in patients with acute STEMI.
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Vecchio S, Varani E, Chechi T, Balducelli M, Vecchi G, Aquilina M, Ricci Lucchi G, Dal Monte A, Margheri M. Coronary thrombus in patients undergoing primary PCI for STEMI: Prognostic significance and management. World J Cardiol 2014; 6:381-392. [PMID: 24976910 PMCID: PMC4072828 DOI: 10.4330/wjc.v6.i6.381] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2013] [Revised: 03/26/2014] [Accepted: 04/11/2014] [Indexed: 02/06/2023] Open
Abstract
Acute ST-elevation myocardial infarction (STEMI) usually results from coronary atherosclerotic plaque disruption with superimposed thrombus formation. Detection of coronary thrombi is a poor prognostic indicator, which is mostly proportional to their size and composition. Particularly, intracoronary thrombi impair both epicardial blood flow and myocardial perfusion, by occluding major coronary arteries and causing distal embolization, respectively. Thus, although primary percutaneous coronary intervention is the preferred treatement strategy in STEMI setting, the associated use of adjunctive antithrombotic drugs and/or percutaneous thrombectomy is crucial to optimize therapy of STEMI patients, by improving either angiographical and clinical outcomes. This review article will focus on the prognostic significance of intracoronary thrombi and on current antithrombotic pharmacological and interventional strategies used in the setting of STEMI to manage thrombotic lesions.
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Abstract
PURPOSE OF REVIEW This article will summarize recent observations that provide mechanistic insight into the molecular and cellular links between inflammation and thrombosis in the context of cardiovascular and other thromboinflammatory disease states. RECENT FINDINGS Several disease conditions are characterized by a thromboinflammatory state in which interactions of blood cells and components with the vascular wall perpetuate both thrombotic and inflammatory pathways. Targeting these pathways may be of benefit in inflammatory conditions and cardiovascular disease. SUMMARY Ongoing clinical trials should provide additional insight into the hypothesis that the thromboinflammatory state contributes to adverse clinical outcomes.
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The CXCR1/2 ligand NAP-2 promotes directed intravascular leukocyte migration through platelet thrombi. Blood 2013; 121:4555-66. [PMID: 23550035 DOI: 10.1182/blood-2012-09-459636] [Citation(s) in RCA: 97] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Thrombosis promotes leukocyte infiltration into inflamed tissues, leading to organ injury in a broad range of diseases; however, the mechanisms by which thrombi guide leukocytes to sites of vascular injury remain ill-defined. Using mouse models of endothelial injury (traumatic or ischemia reperfusion), we demonstrate a distinct process of leukocyte recruitment, termed "directed intravascular migration," specifically mediated by platelet thrombi. Single adherent platelets and platelet aggregates stimulated leukocyte shape change at sites of endothelial injury; however, only thrombi were capable of inducing directed intravascular leukocyte migration. Leukocyte recruitment and migration induced by platelet thrombi occurred most prominently in veins but could also occur in arteries following ischemia-reperfusion injury. In vitro studies demonstrated a major role for platelet-derived NAP-2 (CXCL-7) and its CXCR1/2 receptor in regulating leukocyte polarization and motility. In vivo studies demonstrated the presence of an NAP-2 chemotactic gradient within the thrombus body. Pharmacologic blockade of CXCR1/2 as well as genetic deletion of NAP-2 markedly reduced leukocyte shape change and intrathrombus migration. These studies define a distinct process of leukocyte migration that is initiated by homotypic adhesive interactions between platelets, leading to the development of an NAP-2 chemotactic gradient within the thrombus body that guides leukocytes to sites of vascular injury.
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Yunoki K, Naruko T, Inoue T, Sugioka K, Inaba M, Iwasa Y, Komatsu R, Itoh A, Haze K, Yoshiyama M, Becker AE, Ueda M. Relationship of thrombus characteristics to the incidence of angiographically visible distal embolization in patients with ST-segment elevation myocardial infarction treated with thrombus aspiration. JACC Cardiovasc Interv 2013; 6:377-85. [PMID: 23523458 DOI: 10.1016/j.jcin.2012.11.011] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2012] [Revised: 11/14/2012] [Accepted: 11/21/2012] [Indexed: 01/11/2023]
Abstract
OBJECTIVES This study sought to investigate the association between pathological characteristics of aspirated intracoronary thrombi and the incidence of angiographically visible distal embolization (AVDE) during primary percutaneous coronary intervention (p-PCI) in patients with ST-segment elevation myocardial infarction (STEMI) treated with thrombus aspiration. BACKGROUND AVDE of atherosclerotic and thrombotic material has been shown to impair myocardial perfusion and contribute to poor clinical outcome in patients with STEMI. Recent studies have shown that thrombus composition and size are associated with the incidence of AVDE. METHODS Aspirated thrombi from 164 STEMI patients within 12 h of symptom onset were investigated immunohistochemically using antibodies against platelets, erythrocytes, and inflammatory cells. RESULTS The angiographic results showed that AVDE during p-PCI occurred in 22 (13.4%) patients. Pathological analysis revealed that thrombi from patients with AVDE had a greater erythrocyte-positive area (60 ± 15% vs. 43 ± 21%, p < 0.0005) and more myeloperoxidase-positive cells (943 ± 324 cells/mm(2) vs. 592 ± 419 cells/mm(2), p < 0.0005) than those from patients without AVDE. Thrombus size, quantified as the thrombus surface area, was positively correlated with the erythrocyte component (r = 0.362, p < 0.0001). Moreover, multivariate logistic analysis demonstrated that erythrocyte-positive area in the thrombi, glucose levels on admission, larger vessel diameter (≥ 3.5 mm), and pre-balloon dilation were independent predictors of the incidence of AVDE. CONCLUSIONS This study demonstrated that the erythrocyte-rich component of aspirated thrombi may be associated with the incidence of AVDE during p-PCI in patients with STEMI.
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Affiliation(s)
- Kei Yunoki
- Department of Cardiology, Osaka City General Hospital, Osaka, Japan
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Yunoki K, Naruko T, Sugioka K, Inaba M, Itoh A, Haze K, Yoshiyama M, Ueda M. Thrombus Aspiration Therapy and Coronary Thrombus Components in Patients with Acute ST-Elevation Myocardial Infarction. J Atheroscler Thromb 2013; 20:524-37. [DOI: 10.5551/jat.17608] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
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Ghasemzadeh M, Hosseini E. Platelet-leukocyte crosstalk: Linking proinflammatory responses to procoagulant state. Thromb Res 2012; 131:191-7. [PMID: 23260445 DOI: 10.1016/j.thromres.2012.11.028] [Citation(s) in RCA: 112] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2012] [Revised: 11/20/2012] [Accepted: 11/23/2012] [Indexed: 01/18/2023]
Abstract
Platelet activation is known to be associated with the release of a vast array of chemokines and proinflammatory lipids which induce pleiotropic effects on a wide variety of tissues and cells, including leukocytes. During thrombosis, the recruitment of leukocytes to activated platelets is considered an important step which not only links thrombosis to inflammatory responses but may also enhance procoagulant state. This phenomenon is highly regulated and influenced by precise mutual interactions between the cells at site of vascular injury and thrombi formation. Platelet-leukocyte interaction involves a variety of mediators including adhesion molecules, chemokines and chemoattractant molecules, shed proteins, various proinflammatory lipids and other materials. The current review addresses the detailed mechanisms underlying platelet-leukocyte crosstalk. This includes their adhesive interactions, transcellular metabolisms, induced tissue factor activity and neutrophil extracellular traps formation as well as the impacts of these phenomena in modulation of the proinflammatory and procoagulant functions in a reciprocal manner that enhances the physiological responses.
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Affiliation(s)
- Mehran Ghasemzadeh
- Australian Centre for Blood Diseases, Monash University, Melbourne, Australia
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Yunoki K, Naruko T, Sugioka K, Inaba M, Iwasa Y, Komatsu R, Itoh A, Haze K, Inoue T, Yoshiyama M, Becker AE, Ueda M. Erythrocyte-rich thrombus aspirated from patients with ST-elevation myocardial infarction: association with oxidative stress and its impact on myocardial reperfusion. Eur Heart J 2012; 33:1480-90. [PMID: 22240493 DOI: 10.1093/eurheartj/ehr486] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
AIMS Recent studies have demonstrated that erythrocytes are a potential component in atheromatous lesions and thrombus formation in patients with ST-elevation myocardial infarction (STEMI). The purpose of this study was to determine the associations of red blood cell (RBC) component of coronary thrombi with oxidative stress and myocardial reperfusion. METHODS AND RESULTS Aspirated thrombi from 178 STEMI patients within 12 h of symptom onset were investigated immunohistochemically using antibodies against platelets, RBCs, fibrin, macrophages, and neutrophils [myeloperoxidase (MPO)]. The thrombi were divided into tertiles according to the percentage of glycophorin-A-positive area: low (glycophorin-A-positive area <33%; n = 60), intermediate (<54 to 33%; n = 59), and high group (≥54%; n = 59). We also measured plasma MPO levels on admission. In the thrombi, the number of MPO-positive cells in the high-RBC group was significantly greater than that in the low-RBC group (high, 927 ± 385; intermediate, 765 ± 406; low, 279 ± 220 cells/mm(2); P< 0.0001). Plasma MPO levels were significantly higher in the high-RBC group than that in the low-RBC group [low 43.1 (25.0-71.6); intermediate 71.0 (32.9-111.2); high 74.3 (31.1-126.4)ng/mL; P< 0.005]. Distal embolization occurred more frequently in the high-RBC group (P= 0.0009). Moreover, the signs of impaired myocardial reperfusion, as indicated by incomplete ST-segment resolution (STR) and lower myocardial blush grades (MBG), and progression of left ventricular remodelling at 6 months were frequently observed in the high-RBC group (high vs. low: STR, P= 0.056; MBG, P< 0.01; remodelling, P< 0.01). CONCLUSION The present study demonstrated that erythrocyte-rich thrombi contain more inflammatory cells and reflect high thrombus burden, leading to impaired myocardial reperfusion in STEMI patients.
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Affiliation(s)
- Kei Yunoki
- Department of Cardiology, Osaka City General Hospital, Osaka, Japan
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Activated inflammatory cells participate in thrombus size through tissue factor and plasminogen activator inhibitor-1 in acute coronary syndrome: Immunohistochemical analysis. Thromb Res 2011; 127:443-9. [DOI: 10.1016/j.thromres.2011.02.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2010] [Revised: 01/24/2011] [Accepted: 02/03/2011] [Indexed: 11/20/2022]
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Uchida Y, Uchida Y, Sakurai T, Kanai M, Shirai S, Morita T. Characterization of coronary fibrin thrombus in patients with acute coronary syndrome using dye-staining angioscopy. Arterioscler Thromb Vasc Biol 2011; 31:1452-60. [PMID: 21415387 DOI: 10.1161/atvbaha.110.221671] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
OBJECTIVE Because fibrin is transparent and almost invisible by any conventional imaging methodologies, clinical examinations of coronary fibrin thrombus have been ignored, and little is known about its role in the genesis of acute coronary syndrome (ACS). The present study was performed to visualize coronary fibrin thrombus and to examine its role in ACS. METHODS AND RESULTS Dye-staining coronary angioscopy using Evans blue dye, which selectively stains fibrin blue but does not stain blood corpuscles, was performed for observation of globular coronary thrombi in 111 ACS patients. The thrombi were aspirated for histological examination. The thrombi were classified by visual appearance into 8 transparent, 3 light-red, 2 frosty glass-like and membranous, 32 white, 8 brown, 34 red, and 19 red-and-white in a mosaic pattern. Transparent thrombi that were not visible by conventional angioscopy were visualized as a blue structure by dye-staining angioscopy, and they were observed in patients with unstable angina (UA) and non-ST elevation myocardial infarction (NSTEMI). The thrombi caused total or subtotal coronary occlusion. The aspirated thrombi were composed of fibrin alone by histology. Fibrin-rich thrombi were visualized using dye-staining angioscopy in 60% of 50 patients with UA+NSTEMI and in 29% of 61 patients with ST-elevation myocardial infarction. By histology of the aspirated thrombi, fibrin-rich thrombi were observed in 71% of 33 patients with UA+NSTEMI and in 28% of 35 patients with ST-elevation myocardial infarction. CONCLUSION Fibrin-rich coronary thrombi were frequently observed by both dye-staining angioscopy and histology in ACS patients. Rarely, fibrin itself formed a globular thrombus and caused coronary occlusion.
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Affiliation(s)
- Yasumi Uchida
- Japan Foundation for Cardiovascular Research, Funabashi, Japan.
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Lee HY, Kim JH, Kim BO, Kang YJ, Ahn HS, Hwang MW, Park KM, Byun YS, Goh CW, Rhee KJ. Effect of Aspiration Thrombectomy on Microvascular Dysfunction in ST-Segment Elevation Myocardial Infarction With an Elevated Neutrophil Count. Korean Circ J 2011; 41:68-75. [PMID: 21430991 PMCID: PMC3053563 DOI: 10.4070/kcj.2011.41.2.68] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2010] [Revised: 06/22/2010] [Accepted: 07/19/2010] [Indexed: 11/11/2022] Open
Abstract
Background and Objectives Aspiration thrombectomy (AT) during primary percutaneous coronary intervention (PCI) is an effective adjunctive therapy for ST-segment elevation myocardial infarction (STEMI). An elevated neutrophil count in STEMI is associated with microvascular dysfunction and adverse outcomes. We evaluated whether AT can improve microvascular dysfunction in patients with STEMI and an elevated neutrophil count. Subjects and Methods Seventy patients with STEMI undergoing primary PCI from August 2007 to February 2009 in our institution were classified by tertiles of neutrophil count on admission (<5,300/mm3, 5,300-7,600/mm3, and >7,600/mm3). The angiographic outcome was post-procedural thrombolysis in myocardial infarction (TIMI) flow grade. Microvascular dysfunction was assessed by TIMI myocardial perfusion (TMP) grade and ST-segment resolution on electrocardiography 90 minutes after PCI. The clinical outcome was major adverse cardiac event (MACE), defined as cardiac death, re-infarction, and target lesion revascularization at 9 months. Results There were no significant differences in the clinical characteristics and pre- and post-procedural TIMI flow grades between the neutrophil tertiles. As the neutrophil count increased, a lower tendency toward TMP grade 3 (83% vs. 52% vs. 54%, p=0.06) and more persistent residual ST-segment elevation (>4 mm: 13% vs. 26% vs. 58%, p=0.005) was observed. The 9-month MACE rate was similar between the groups. On subgroup analysis of AT patients (n=52) classified by neutrophil tertiles, the same tendency toward less frequent TMP grade 3 (77% vs. 56% vs. 47%, p=0.06) and persistent residual ST-segment elevation (>4 mm: 12% vs. 28% vs. 53%, p=0.05) was observed as neutrophil count increased. Conclusion A higher neutrophil count at presentation in STEMI is associated with more severe microvascular dysfunction after primary PCI, which is not improved with AT.
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Affiliation(s)
- Hye Young Lee
- Division of Cardiology, Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea
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Ito N, Nanto S, Doi Y, Kurozumi Y, Tonomura D, Natsukawa T, Sawano H, Masuda D, Yamashita S, Okada KI, Hayashi Y, Kai T, Hayashi T. Distal Protection During Primary Coronary Intervention Can Preserve the Index of Microcirculatory Resistance in Patients With Acute Anterior ST-Segment Elevation Myocardial Infarction. Circ J 2011; 75:94-8. [DOI: 10.1253/circj.cj-10-0133] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Noritoshi Ito
- Senri Critical Care Medical Center, Critical & Cardiovascular Care Unit, Osaka Saiseikai Senri Hospital
| | - Shinsuke Nanto
- Department of Advanced Cardiovascular Therapeutics, Osaka University Graduate School of Medicine
| | - Yasuji Doi
- Division of Cardiovascular Medicine, Critical & Cardiovascular Care Unit, Osaka Saiseikai Senri Hospital
| | - Yuma Kurozumi
- Senri Critical Care Medical Center, Critical & Cardiovascular Care Unit, Osaka Saiseikai Senri Hospital
| | - Daisuke Tonomura
- Senri Critical Care Medical Center, Critical & Cardiovascular Care Unit, Osaka Saiseikai Senri Hospital
| | - Tomoaki Natsukawa
- Senri Critical Care Medical Center, Critical & Cardiovascular Care Unit, Osaka Saiseikai Senri Hospital
| | - Hirotaka Sawano
- Senri Critical Care Medical Center, Critical & Cardiovascular Care Unit, Osaka Saiseikai Senri Hospital
| | - Daisaku Masuda
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine
| | - Shizuya Yamashita
- Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine
| | - Ken-ichiro Okada
- Division of Cardiovascular Medicine, Critical & Cardiovascular Care Unit, Osaka Saiseikai Senri Hospital
| | - Yasuyuki Hayashi
- Senri Critical Care Medical Center, Osaka Saiseikai Senri Hospital
| | - Tatsuro Kai
- Senri Critical Care Medical Center, Osaka Saiseikai Senri Hospital
| | - Toru Hayashi
- Division of Cardiovascular Medicine, Critical & Cardiovascular Care Unit, Osaka Saiseikai Senri Hospital
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Katashima T, Naruko T, Terasaki F, Fujita M, Otsuka K, Murakami S, Sato A, Hiroe M, Ikura Y, Ueda M, Ikemoto M, Kitaura Y. Enhanced expression of the S100A8/A9 complex in acute myocardial infarction patients. Circ J 2010; 74:741-748. [PMID: 20190427 DOI: 10.1253/circj.cj-09-0564] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND S100A8/A9 complex (S100A8/A9) is expressed in activated human neutrophils and macrophages. Enhanced expression of S100A8/A9 in atherosclerotic plaque of patients with unstable angina pectoris (UAP) has been demonstrated, but its profile in acute myocardial infarction (AMI) has not been clarified. METHODS AND RESULTS Serum S100A8/A9 levels were serially measured in patients with AMI (n=55) and UAP (n=16) during the acute period. The expression of S100A8/A9 was examined immunohistochemically in the infarcted myocardium of 7 autopsied patients with AMI. Serum S100A8/A9 levels on the 1st day were 1,118+/-115 (SE) ng/ml in AMI patients as compared with 787+/-147 ng/ml in UAP patients. On days 3-5, serum S100A8/A9 levels in AMI patients reached a peak value and were significantly higher than the values in UAP patients (1,690+/-144 ng/ml vs 844+/-100 ng/ml; P<0.0001). In AMI patients, peak S100A8/A9 levels positively correlated with peak white blood cell and neutrophil counts, and peak creatine kinase-MB and peak C-reactive protein levels. Double immunostaining revealed that S100A8/A9 was specifically expressed in neutrophils and macrophages infiltrating the infarcted myocardium. CONCLUSIONS S100A8/A9 is implicated in the pathophysiology of AMI and may be an additional biomarker of the local inflammatory response following AMI.
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Affiliation(s)
- Takashi Katashima
- Department of Internal Medicine III, Osaka Medical College, Takatsuki, Japan
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Heusch G, Kleinbongard P, Böse D, Levkau B, Haude M, Schulz R, Erbel R. Coronary microembolization: from bedside to bench and back to bedside. Circulation 2009; 120:1822-36. [PMID: 19884481 DOI: 10.1161/circulationaha.109.888784] [Citation(s) in RCA: 329] [Impact Index Per Article: 20.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Coronary microembolization from the erosion or rupture of a vulnerable atherosclerotic plaque occurs spontaneously in acute coronary syndromes and iatrogenically during percutaneous coronary interventions. Typical consequences of coronary microembolization are microinfarcts with an inflammatory response, contractile dysfunction, and reduced coronary reserve. Apart from transient elevations of creatine kinase and troponin, microemboli can be visualized by intracoronary Doppler and the resulting microinfarcts by late-enhancement nuclear magnetic resonance. Statins, antiplatelet agents, and coronary vasodilators protect against microembolization and microinfarction when started before percutaneous coronary interventions. Distal protection devices can retrieve atherothrombotic debris and prevent its embolization into the microcirculation, but their effect on clinical outcome has been disappointing so far, except for saphenous vein bypass grafts. Devices for aspiration of thrombi and thrombus-derived vasoconstrictor, thrombogenic, and inflammatory substances, however, reduce thrombus burden, improve perfusion, and provide protection in patients with acute myocardial infarction.
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Affiliation(s)
- Gerd Heusch
- Institut für Pathophysiologie, Universitätsklinikum Essen, Essen, Germany.
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Yasuda S, Shimokawa H. Acute Myocardial Infarction The Enduring Challenge for Cardiac Protection and Survival. Circ J 2009; 73:2000-8. [DOI: 10.1253/circj.cj-09-0655] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Satoshi Yasuda
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
| | - Hiroaki Shimokawa
- Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine
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