Observational Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Dec 26, 2017; 9(12): 822-829
Published online Dec 26, 2017. doi: 10.4330/wjc.v9.i12.822
Endothelin-1 activation in pediatric patients undergoing surgical coarctation of the aorta repair
Benjamin Steven Frank, Tracy T Urban, Suhong Tong, Courtney Cassidy, Max B Mitchell, Christopher S Nichols, Jesse A Davidson
Benjamin Steven Frank, Jesse A Davidson, Division of Cardiology, Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, United States
Tracy T Urban, Children’s Hospital Colorado Research Institute, Aurora, CO 80045, United States
Suhong Tong, Department of Biostatistics, University of Colorado Denver, Aurora, CO 80045, United States
Courtney Cassidy, Department of Pediatric Cardiology, Children’s Hospital Colorado, Aurora, CO 80045, United States
Max B Mitchell, Department of Surgery, University of Colorado Denver, Aurora, CO 80045, United States
Christopher S Nichols, Department of Anesthesiology, University of Colorado Denver, Aurora, CO 80045, United States
Author contributions: Frank BS and Davidson JA primarily designed the research; Urban TT, Tong S, Cassidy C, Mitchell MB and Nichols CS contributed to study conception and design; Frank BS and Urban TT collected the clinical data; Cassidy C collected and analyzed the echocardiographic data; Tong S performed the statistical analysis; Frank BS and Davidson JA primarily wrote the article; Urban TT, Tong S, Cassidy C, Mitchell MB and Nichols CS contributed to editing, reviewing, and final approval of the article.
Supported by NIH/NCATS Colorado CTSA, No. UL1 TR00 1082-04. Contents are the authors’ sole responsibility and do not necessarily represent official NIH views. The study sponsor had no input into the study design, collection, analysis, and interpretation of data, the writing of the report, and the decision to submit the paper for publication.
Institutional review board statement: This study was reviewed and approved by the Colorado Multiple Institution Review Board.
Informed consent statement: Written informed consent was obtained from the study subjects’ parents in all cases. Written assent was obtained from all subjects aged between seven years and eighteen years.
Conflict-of-interest statement: The authors have no conflicts of interest to disclose. Dr. Davidson is supported by NIH/NHLBI 1K23HL123634. This funding source was not used to generate the data presented in this manuscript.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Benjamin Steven Frank, MD, Academic Fellow, Division of Cardiology, Department of Pediatrics, University of Colorado Denver, 13123 E. 16th Ave, Box B100, Aurora, CO 80045, United States. benjamin.frank@childrenscolorado.org
Telephone: +1-720-7771954 Fax: +1-720-7777290
Received: August 24, 2017
Peer-review started: August 25, 2017
First decision: September 25, 2017
Revised: October 21, 2017
Accepted: November 10, 2017
Article in press: November 10, 2017
Published online: December 26, 2017
Processing time: 119 Days and 4.2 Hours
ARTICLE HIGHLIGHTS
Research background

Patients with coarctation of the aorta are at risk for a variety of short- and long-term complications after surgical repair. Endothelin-1 (ET-1) is a peptide hormone known to cause both cardiac myocyte hypertrophy and vasoconstriction that has been linked to late ventricular hypertrophy in this population. Peri-operative endothelin concentration in this population has not been previously defined.

Research motivation

Defining ET-1 activation in the perioperative period could offer significant insight into the variable short and long term physiologic responses to coarctation seen in this population.

Research objectives

The authors sought to define pre-operative ET-1 activation, perioperative changes in concentrations with surgical relief, and the association with early myocardial change.

Research methods

Here authors present a prospective, cohort study of ET-1 concentration and pathologic myocardial remodeling both prior to surgical correction of coarctation/aortic arch obstruction and in the immediate post-operative period. ET-1 analysis was performed by ELISA. Echocardiograms were obtained immediately prior to surgical repair and between 24 and 72 h post-operatively. All images were obtained with a GE Vivid E9 or E95 machine (General Electric, Chicago, Ill). Relative wall thickness (RWT) was measured at end-diastole from the parasternal short axis view as the ratio of the sum of the posterior and septal mural thickness to the left ventricular internal end-diastolic diameter; a value of 41% is conventionally taken as the upper limit of normal for RWT. LV mass was calculated by the area-length (AL) method, indexed to height2.7, and compared to previously published normal values.

Research results

The authors demonstrate that neonates with coarctation of the aorta have high pre-operative ET-1 levels that decrease post-operatively. Older coarctation patients have more modest ET-1 activation that is unchanged post-operatively.

Research conclusions

This study is the first to assess early ET-1 activation and its association with LV remodeling at the time of surgery for coarctation of the aorta. Key findings include increased concentration among neonates preoperatively with a decline after anatomic correction. This pattern is contrasted with more modest ET-1 level before surgery in older children and no significant post-operative change. The authors find preliminary evidence supporting two potentially distinct stimuli for ET-1: One mechanism, associated with high LV afterload and sympathetic nervous system activation, persists through the immediate post-operative period and the other, likely driven by altered pulmonary artery physiology, is rapidly reversible. The authors further find preliminary evidence supporting an association between ET-1 activity and early pathologic LV remodeling.

Research perspectives

Longitudinal studies will be needed to evaluate ET-1’s role both in myocyte hypertrophy prior to repair and reverse remodeling after surgical correction. Given the normal pulmonary hemodynamics in the author’s older cohort and the mechanistic explanation offered by previous work, the authors posit that the ET-1 levels seen in this sub-group could reflect sympathetic activation due to the abnormality in LV and systemic vascular physiology. Future studies will be needed to confirm this hypothesis. The variable activation pattern between neonatal and older patients supports a role for the different pulmonary artery mechanics between the two subgroups affecting the variable ET-1 levels seen. Further studies will be needed to clarify the role of pulmonary artery pressure and pulmonary blood flow on ET-1 concentration.