Background
Age and acute hyperglycemia are known risk factors for myocardial ischemia-reperfusion injury and combined frequently in clinical circumstances. However, there are limited data to examine myocardial ischemia-reperfusion injury in animal models exhibiting these co-morbidities concomitantly. Thus, we investigated the effect of acute hyperglycemia on myocardial ischemia-reperfusion injury in different age-groups and possible mechanisms. 

Methods
Three different age groups of male Sprague Dawley rats were included (young-aged, 3 months; middle-aged, 10-12 months; and old-aged, 20-22 months). Rats received 1.2 g/kg of dextrose (hyperglycemic group) or same volume of normal saline (normoglycemic group) according to the group. Rats were subjected to coronary artery occlusion for 45 min followed by reperfusion for 240 min. By measuring the infarct size and ejection fraction, we estimated the susceptibility to ischemia-reperfusion injury in rat. Proteins related to apoptosis (C-PARP, Bcl-2, Bax, and cytochrome C) and autophagy (Bnip3, Beclin-1, Atg5r, and LC3B-II) were evaluated by western blot assay.

Results
Infarct size was increased by acute hyperglycemia in young- and middle-aged rats but not in old-aged rats, while reduction of ejection fraction after ischemia-reperfusion was aggravated by acute hyperglycemia in all age groups. Acute hyperglycemia increased expression of Bnip3 and Beclin-1 after ischemia-reperfusion in young- and middle-aged rats but not in old-aged rats. Also, increased expression of Bax, Cytochrome C, Atg5, and LC3B-II by acute hyperglycemia occurred only in young- or middle-aged rats.   

Conclusion
The results of current study demonstrated that acute hyperglycemia did not aggravate myocardial ischemia-reperfusion injury in old-aged rats, unlike young and middle-aged rats. This heterogeneity may be a consequence of attenuation in changes of apoptotic and autophagic signalling after ischemia-reperfusion injury under acute hyperglycemia in old-aged heart.


10 / Age-related difference in the effect of acute hyperglycemia on myocardial ischemia-reperfusion injury