Abstract 11718: Extracellular Matrix Implantation Prevents Left Ventricular Paradoxical Systolic Bulging and Postinfarction Remodeling in Rats Independent of Cardiac Stem Cell Recruitment
BACKGROUND: Biomaterial implantation provides a promising approach to limit adverse remodelling following myocardial infarction (MI). In this study, we determined whether implantation of heart tissue-derived decellularized extracellular matrix (ECM), which contains native biochemical and structural matrix composition, could prevent left ventricular (LV) paradoxical systolic bulging and post-MI remodeling by thickening the infarcted wall in a rat MI model.
METHODS: ECM was derived from rat hearts. MI was induced by left coronary ligation in Fischer rats. One week later, saline (75 μl, n=17) or matrix (75 μl, n=19) was directly injected into the infarcted area. Cardiac function and the infarct wall motion were assessed by left ventriculogram at 6 weeks after injection, and the hearts were harvested and processed for histology.
RESULTS: The average infarcted LV wall was 24.4% thicker in the ECM- treated group than in the saline-treated group (p=0.0084) and infarct expansion index was reduced by 23.9% in the ECM group (p=0.0058). The thickness of the infarcted wall even at its thinnest point was 0.43 ± 0.03 mm in ECM group versus 0.32 ± 0.03 mm in saline group (p=0.01). The infarct size was similar between the saline group (48.0 ± 1.2 %) and ECM group (45.7 ± 2.2 %, p=0.37). The density of blood vessels within the scar area was 189±12 vessels/mm2 in the saline group and 165±23 vessels/mm2 in the ECM group (P=NS). Immunohistochemical c-kit staining demonstrated that the number of c-kit+ cells was similar between the saline group (105±13 positive stained cells per 200× image field) and ECM-treated group (111±11 positive stained cells per 200× image field, P=NS). Left ventriculogram demonstrated that paradoxical LV systolic bulging was significantly reduced in the ECM-treated group (6.2 ± 1.6% of the LV circumference) compared to the saline-treated group (10.3 ± 1.3%; p=0.048), and ECM treatment increased LV ejection fraction by 4.3%compared to saline treatment (p=0.043).
CONCLUSIONS: ECM treatment thickens the LV infarcted wall, prevents paradoxical LV systolic bulging and remodeling, and improves cardiac function after MI in rats. This benefit was not dependent upon enhanced angiogenesis or the recruitment of endogenous stem cells to the injury site.
- © 2012 by American Heart Association, Inc.