Epicardial infarct repair with basic fibroblast growth factor–enhanced CorMatrix-ECM biomaterial attenuates postischemic cardiac remodeling

Abstract

Dysregulation of extracellular matrix (ECM) following myocardial infarction is a key contributor to myocardial fibrosis, chamber dilation, and progression to heart failure. Basic fibroblast growth factor is a potent inhibitor of fibrosis. We propose a novel surgical procedure leveraging a commercially available ECM biomaterial for the treatment of ischemic heart failure. Epicardial infarct repair using CorMatrix-ECM biomaterial patch (CorMatrix Cardiovascular Inc, Roswell, Ga) was compared with sham in a rat myocardial infarction model. Key indices of ischemic remodeling, including inflammation, fibrosis, and myocardial performance were evaluated 16 weeks post-treatment. Histology and immunohistochemistry demonstrated comprehensive integration of CorMatrix-ECM biomaterial patch without evidence of immune reaction and an increase in basic fibroblast growth factor expression in treated animals. Functional analysis by serial echocardiography of normal (n=13), sham (n=15), nonenhanced CorMatrix-ECM patch (n=18), and basic fibroblast growth factor-enhanced CorMatrix-ECM patch (n=10) animals revealed an improvement in ejection fraction in basic fibroblast growth factor-enhanced CorMatrix-ECM patch animals compared with shams (55.3% ± 8.0% vs 35.1% ± 7.6%; P<.001). Prevention of left ventricle remodeling was also confirmed by pressure volume loop analysis, which demonstrated reduced left ventricular end diastolic volumes in basic fibroblast growth factor-enhanced CorMatrix-ECM patch animals (n=5) compared with shams (n=6) (208.0 ± 59.3 μL vs 363. 1 ± 108.7 μL; P<.01) and improved left ventricle contractility in nonenhanced CorMatrix-ECM patch (n=7) and basic fibroblast growth factor-enhanced CorMatrix-ECM patch animals compared with shams (0.709 ± 0.306 and 0.609 ± 0.160 vs 0.437 ± 0.218; P<.05). Epicardial infarct repair with basic growth factor-enhanced CorMatrix-ECM biomaterial patch attenuates myocardial remodeling and improves cardiac performance after subacute myocardial infarction in a rat coronary ligation model. These observations establish proof-of-concept for this novel surgical approach.