Epicardial infarct repair with bioinductive extracellular matrix promotes vasculogenesis and myocardial recovery

Holly E M Mewhort, Jeannine D Turnbull, Alessandro Satriano, Kelvin Chow, Jacqueline A Flewitt, Adin-Cristian Andrei, David G Guzzardi, Daniyil A Svystonyuk, James A White, Paul W M Fedak, Holly E M Mewhort, Jeannine D Turnbull, Alessandro Satriano, Kelvin Chow, Jacqueline A Flewitt, Adin-Cristian Andrei, David G Guzzardi, Daniyil A Svystonyuk, James A White, Paul W M Fedak

Abstract

Background: Infarcted myocardium can remodel after successful reperfusion, resulting in left ventricular dilation and heart failure. Epicardial infarct repair (EIR) using a bioinductive extracellular matrix (ECM) biomaterial is a novel surgical approach to promote endogenous myocardial repair and functional recovery after myocardial infarction. Using a pre-clinical porcine model of coronary ischemia-reperfusion, we assessed the effects of EIR on regional functional recovery, safety, and possible mechanisms of benefit.

Methods: An ECM biomaterial (CorMatrix ECM) was applied to the epicardium after 75 minutes of coronary ischemia in a porcine model. Following ischemia-reperfusion injury, animals were randomly assigned in 2:1 fashion to EIR (n = 8) or sham treatment (n = 4). Serial cardiac magnetic resonance imaging was performed on normal (n = 4) and study animals at baseline (1 week) and 6 weeks after treatment. Myocardial function and tissue characteristics were assessed.

Results: Functional myocardial recovery was significantly increased by EIR compared with sham treatment (change in regional myocardial contraction at 6 weeks, 28.6 ± 14.0% vs 4.2 ± 13.5% wall thickening, p < 0.05). Animals receiving EIR had reduced adhesions compared with animals receiving sham treatment (1.44 ± 0.51 vs 3.08 ± 0.89, p < 0.05). Myocardial fibrosis was not increased, and EIR did not cause myocardial constriction, as left ventricular compliance by passive pressure distention at matched volumes was similar between groups (13.9 ± 4.0 mm Hg in EIR group vs 16.0 ± 5.2 mm Hg in sham group, p = 0.61). Animals receiving EIR showed evidence of vasculogenesis in the region of functional recovery.

Conclusions: In addition to the beneficial effects of successful reperfusion, EIR using a bioinductive ECM enhances myocardial repair and functional recovery. Clinical translation of EIR early after myocardial infarction as an adjunct to surgical revascularization may be warranted in the future.

Keywords: angiogenesis; cardiac MRI; extracellular matrix; heart failure; ischemia-reperfusion; myocardial infarction.

Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Source: PubMed

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