Apical Resection Prolongs the Cell Cycle Activity and Promotes Myocardial Regeneration After Left Ventricular Injury in Neonatal Pig
Meng Zhao, Éric Zhang, Yuhua Wei, Yang Zhou, Gregory P. Walcott, Jianyi Zhang
Abstract
stem cells swine A dult mammals are unable to regenerate the cardiac muscle lost to myocardial injury. 1 However, we have previously shown that hearts of neonatal pigs can recover from acute myocardial infarction (MI) occurring on postnatal day (P) 1, with little evidence of scar formation or wall thinning 30 days later, 1,2 and cardiac tissue removed during apical resection in P1 mice was shown to have fully regenerated 3 weeks later. 1 Because the primary mechanism of regeneration in both early postnatal animal species appeared to involve the proliferation of preexisting cardiomyocytes located near the injury site, we were curious whether the proliferative cardiomyocytes could be induced to undergo further proliferation after a second cardiac injury. We hypothesized that because of the state of activated cellular proliferation machinery in the proliferative cardiomyocytes and potential extension of the developmentally regulated cardiomyocyte proliferative window resulting from activation of injury repair mechanisms, a second injury induced by left anterior descending coronary artery (LAD) ligation distal to the second diagonal 4 weeks after initial apex resection (AR) at P1 (AR+MI) would result in significantly less myocardial structural and functional damage when evaluated 4 weeks later.