Abstract 3951: Acarbose, an Alpha-Glucosidase Inhibitor, Reduces Myocardial Infarct Size by Preventing Postprandial Hyperglycemia and Decreasing Oxyradicals and Opening the Mitochondrial KATP Channels in Rabbits
Background: Acarbose, an anti-diabetic drug, is an α-glucosidase inhibitor that can inhibit glucose absorption in the intestine. We previously reported that acarbose can reduce myocardial infarct size. Since repetitive postprandial hyperglycemia produces oxyradicals and blocks mitochondrial KATP channels, prevention of postprandial hyperglycemia may decrease production of oxyradicals and open the mitochondrial KATP channels. Therefore, we examined whether acarbose reduces myocardial infarct size by preventing postprandial hyperglycemia, decreasing production of oxyradicals and opening the mitochondrial KATP channels.
Methods and Results: Japanese white rabbits underwent 30 min of coronary occlusion followed by 48 h reperfusion. Rabbits were assigned randomly to five groups: the control group (n=10, fed with normal chow for 7 days), the acarbose group (n=10, fed with 30mg acarbose/100g chow for 7 days), the acarbose+5HD group (n=10, fed the same as the acarbose group and i.v. 5mg/kg of 5-hydroxydecanoate, a mitochondrial KATP channel blocker, 10 min before ischemia), and the sucrose group (n=10, fed with 8g sucrose/100g chow for 7 days) and the acarbose+sucrose group (n=10, fed with 30mg acarbose and 8g sucrose/100g chow). Postprandial blood glucose levels was highest in the sucrose group and higher in the control groups, but decreased in the sucrose+acarbose and acarbose groups. The infarct size as a percentage of the left ventricular risk area determined by 1% Evans blue dye and 1% TTC staining was reduced significantly in the sucrose+acarbose group(19.0±5.6%) and acarbose group (19.4±2.3%) as compared with that in the sucrose group (47.4±4.2%) and control group (42.8±5.4%). Myocardial interstitial 2,5-DHBA levels, an indicator of hydroxyl radicals, increased during reperfusion after 30 min of ischemia but this increase was inhibited in the acarbose group. The infarct size-reducing effect of acarbose was abolished by 5HD (43.4±4.7%).
Conclusions: Acarbose reduces myocardial infarct size by preventing postpran-dial hyperglycemia and decreasing oxyradicals and opening the mitochondrial KATP channels in rabbits. This finding may provide new insight into therapeutic strategies for diabetic patients with coronary heart disease.