The Role of Autophagy During Myocardial Ischemia/Reperfusion Injury

Autophagy is a housekeeping process to degrade protein aggregates, damaged cytoplasmic constituents, and provides adaptation when cells go through a nutrient stress. However, a debate persists on whether autophagy is beneficial to attenuate or promote cell damage under an ischemia/reperfusion (I/R) insult to the heart. This study tested the effects of an autophagy enhancer (e.g. rapamycin and trehalose) on heart function and infarct size after global ischemia (30 min)/reperfusion (45 min) when given prior to ischemia (pretreatment) or at the beginning of reperfusion (posttreatment). We found that rapamycin pretreatment (25 nM, n=5) significantly restored left ventricular developed pressure (LVDP) to 64±5 % of initial baseline compared to control I/R hearts (n=8) which only recovered to 31±10% of initial baseline (p<0.01). Likewise, trehalose pretreatment (5 mM, n=7) and posttreatment (5 mM, n=6) significantly restored final LVDP to 62±5% and 65±4% of initial baseline, respectively compared to control I/R hearts (both p<0.01). Moreover, infarction percentage after I/R is significantly reduced in rapamycin post-treated hearts (23±4%, p<0.05) and trehalose treated hearts (20±4% for pretreatment and 15±3% for posttreatment, both p<0.01) when compared to control I/R hearts (41±4%). The preliminary data suggest that autophagy enhancement before ischemia or at reperfusion may be beneficial for reducing I/R injury.

This study was supported by the Center for Chronic Disorders of Aging, the Division of Research and the Department of Bio-Medical Sciences at Philadelphia College of Osteopathic Medicine.