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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Campbell Cardiovascular Translational Research Program, Division of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada.
Holly E M
HE
Mewhort
Campbell Cardiovascular Translational Research Program, Division of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada.
Jeannine D
JD
Turnbull
Campbell Cardiovascular Translational Research Program, Division of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada.
H Christopher
HC
Meijndert
Campbell Cardiovascular Translational Research Program, Division of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada.
Janet M C
JM
Ngu
Campbell Cardiovascular Translational Research Program, Division of Cardiac Surgery, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada. Electronic address: paul.fedak@gmail.com.
Paul W M
PW
Fedak
D000818:Animals; D001672:Biocompatible Materials; D006348:Cardiac Surgical Procedures; D004195:Disease Models, Animal; D004337:Drug Carriers; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D005355:Fibrosis; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D020127:Recovery of Function; D012038:Regeneration / Q000187:drug effects*; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects*
D001672:Biocompatible Materials; D004337:Drug Carriers; D016222:Fibroblast Growth Factor 2