Age-Related Difference in the Effect of Acute Hyperglycemia on Myocardial Ischemia-Reperfusion Injury

Abstract

Age and acute hyperglycemia are known risk factors of myocardial ischemia-reperfusion injury. We investigated age-related difference in the effect of acute hyperglycemia on myocardial ischemia-reperfusion injury in Sprague-Dawley rats (young, 3 months; middle-aged, 10-12 months; and old, 22-24 months). The rats received 1.2 g/kg dextrose or normal saline and were subjected to coronary artery occlusion for 45 minutes followed by reperfusion for 240 minutes. Infarct size and ejection fraction were measured. The levels of apoptosis-related proteins (C-PARP, Bcl-2, Bax, and cytochrome c) and autophagy-related proteins (Bnip3, Beclin-1, Atg5, and LC3B-II) were evaluated. Infarct size increased with acute hyperglycemia in young and middle-aged rats but not in old rats, whereas the reduction of ejection fraction after ischemia-reperfusion was aggravated by acute hyperglycemia in all age groups. Acute hyperglycemia increased Bnip3 and Beclin-1 expressions after ischemia-reperfusion in young and middle-aged rats but not in old rats, whereas it increased the expression of Bax, cytochrome c, Atg5, and LC3B-II only in young or middle-aged rats. Conclusively, acute hyperglycemia does not aggravate myocardial ischemia-reperfusion injury in old rats, unlike in young and middle-aged rats. This heterogeneity may be due to attenuated changes in protein signaling after ischemia-reperfusion injury under acute hyperglycemia in old rats.