Abstract 20205: Role of Cardiomyocyte Regeneration in Mechanical Unloading Induced Reverse Cardiac Remodeling

Background: Mechanical unloading with left ventricular assist devices promotes significant myocardial functional improvement in some heart failure patients. The exact mechanism underlying this phenomenon, described as reverse remodeling, remains poorly characterised. Recent reports suggest that the intrinsic regenerative capacity of the heart might contribute to this recovery. We hypothesise that mechanical unloading of the failing heart following myocardial infarction potentiates the proliferation of new cardiomyocytes. Methods: Syngeneic male Lewis rats weighing 200 to 300g were studied. Acute myocardial infarction was induced by coronary artery ligation. Two broad groups were created. A permanent ligation group (A) and a reperfusion (coronary circulation restored after 90 minutes) group (B). In each group hearts were either loaded (AL or BL) or unloaded (AU or BU). In the loaded subgroup rats were recovered after coronary ligation. In the unloaded subgroup, the infarcted hearts were explanted after 90 minutes and transplanted into the abdomen of healthy recipients via heterotopic abdominal heart transplantation. The recipient’s heart acted as control. Hearts were explanted on day 7 for immunohistochemistry. Results: Twelve rats were studied. There was a significant reduction (24%) in ventricular weight in the unloaded compared to the loaded subgroup (p = 0.026). Coronary reperfusion confers increased proliferative capacity (fig) and this is augmented by mechanical unloading (AL vs BL p = 0.0430, AU vs BU p = 0.0061). There was a 14% increase in cardiomyocyte regeneration with mechanical unloading and proliferating myocytes aggregated mostly around the infarct borderzone. Conclusion: In line with published reports, this data shows that adult cardiomyocytes possess an intrinsic regenerative capacity that is stimulated after myocardial injury. Mechanical unloading in addition to coronary reperfusion might augment this regenerative capacity.