Intramyocardial injection of heart tissue-derived extracellular matrix improves postinfarction cardiac function in rats.
OBJECTIVE
We determined whether implantation of heart tissue-derived decellularized matrix, which contains native biochemical and structural matrix composition, could thicken the infarcted left ventricular (LV) wall and improve LV function in a rat myocardial infarction model.


RESULTS
Myocardial infarction 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. At 6 weeks after injection, cardiac function was assessed by left ventriculogram, echocardiography, and Millar catheter. The hearts were pressure fixed to measure postmortem LV volume and processed for histology. Left ventriculogram demonstrated that LV ejection fraction (EF) was significantly greater in the matrix-treated (56.7% ± 1.4%) than in the saline-treated group (52.4% ± 1.5%; P = .043), and paradoxical LV systolic bulging was significantly reduced in the matrix-treated group (6.2% ± 1.6% of the LV circumference) compared to the saline-treated group (10.3% ± 1.3%; P = .048). Matrix implantation significantly increased the thickness of infarcted LV wall (0.602 ± 0.029 mm) compared to the saline-treated group (0.484 ± 0.03 mm; P = .0084). Infarct expansion index was significantly lower in the matrix-treated group (1.053 ± 0.051) than in the saline-treated group (1.382 ± 0.096, P = .0058). Blood vessel density and c-kit positive staining cells within the infarct area were comparable between the 2 groups.


CONCLUSIONS
Implantation of heart tissue-derived decellularized matrix thickens the LV infarcted wall, prevents paradoxical LV systolic bulging, and improves LV EF after myocardial infarction in rats. This benefit was not dependent on the enhanced angiogenesis or the recruitment of endogenous stem cells to the injury site.
The Heart Institute of Good Samaritan Hospital and Division of Cardiovascular Medicine of the Keck School of Medicine, University of Southern California, Los Angeles, CA 90017, USA. wangdedai@yahoo.com
Wangde
W
Dai
Paul
P
Gerczuk
Yuanyuan
Y
Zhang
Leona
L
Smith
Oleg
O
Kopyov
Gregory L
GL
Kay
Aarne J
AJ
Jyrala
Robert A
RA
Kloner
D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000737:chemistry*; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015552:Injections, Intralesional; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000737:chemistry*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010316:Particle Size; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013318:Stroke Volume / Q000187:drug effects; D014020:Tissue Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
D043925:Angiogenesis Inducing Agents; D015415:Biomarkers; D002316:Cardiotonic Agents; D014020:Tissue Extracts; D019009:Proto-Oncogene Proteins c-kit