Sex-specific and exercise-acquired cardioprotection is abolished by sarcolemmal KATP channel blockade in the rat heart

The present study was conducted to determine whether the infarct sparing effect of shortterm exercise is dependent on the operation of the myocardial sarcolemmal ATP-sensitive K+ (K-ATP) channel. Adult male and female Sprague-Dawley rats were exercised on a motorized treadmill for 5 days. Twenty-four hours following the training or sedentary period, hearts were isolated and exposed to 1 h of regional ischemia followed by 2 h of reperfusion on a modified Langendorf apparatus in the presence or absence of the sarcolemmal K-ATP channel antagonist HMR-1098 (30 mu M). Following the ischemia-reperfusion protocol, infarct size was determined as a percentage of the total ischemic zone at risk (ZAR). Short-term exercise reduced infarct size by 24% in males (32 +/- 2% of ZAR; P < 0.01) and by 18% in females (26 +/- 2% of ZAR; P < 0.05). Sarcolemmal K-ATP channel blockade abolished the training-induced cardioprotection in both males and females, increasing infarct size to 43 +/- 3% and 52 +/- 4% of ZAR, respectively. In the absence of HMR-1098, infarct size was significantly lower in sedentary females than in males (33 +/- 4% vs. 42 +/- 2% of ZAR, respectively; P < 0.01). However, the presence of HMR-1098 abolished this sex difference, increasing infarct size by 58% in the sedentary females (P < 0.01) but having no effect on infarct size in sedentary males. This study demonstrates that the sex-specific and exercise-acquired resistance to myocardial ischemia-reperfusion injury is dependent on sarcolemmal K-ATP activitv during ischemia.