title: Epicardial infarct repair with bioinductive extracellular matrix promotes vasculogenesis and myocardial recovery.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Division of Cardiac Surgery.
authors.forename: Holly E M
authors.initials: HE
authors.lastname: Mewhort
authors.affiliation: Division of Cardiac Surgery.
authors.forename: Jeannine D
authors.initials: JD
authors.lastname: Turnbull
authors.affiliation: Stephenson Cardiovascular MR Centre, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Satriano
authors.affiliation: Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Kelvin
authors.initials: K
authors.lastname: Chow
authors.affiliation: Stephenson Cardiovascular MR Centre, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Flewitt
authors.affiliation: Bluhm Cardiovascular Institute, Northwestern University, Chicago, Illinois.
authors.forename: Adin-Cristian
authors.initials: AC
authors.lastname: Andrei
authors.affiliation: Division of Cardiac Surgery.
authors.forename: David G
authors.initials: DG
authors.lastname: Guzzardi
authors.affiliation: Division of Cardiac Surgery.
authors.forename: Daniyil A
authors.initials: DA
authors.lastname: Svystonyuk
authors.affiliation: Stephenson Cardiovascular MR Centre, Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, University of Calgary, Calgary, Alberta, Canada.
authors.forename: James A
authors.initials: JA
authors.lastname: White
authors.affiliation: Division of Cardiac Surgery; Bluhm Cardiovascular Institute, Northwestern University, Chicago, Illinois. Electronic address: paul.fedak@gmail.com.
authors.forename: Paul W M
authors.initials: PW
authors.lastname: Fedak
mesh_terms: D000818:Animals; D005109:Extracellular Matrix; D006321:Heart; D009200:Myocardial Contraction; D009203:Myocardial Infarction; D015428:Myocardial Reperfusion Injury; D009206:Myocardium; D013552:Swine
keywords: angiogenesis; cardiac MRI; extracellular matrix; heart failure; ischemia-reperfusion; myocardial infarction