ENDOTHELIN-1-INDUCED REDUCTION OF MYOCARDIAL INFARCT SIZE BY ACTIVATION OF ATP-SENSITIVE POTASSIUM CHANNELS IN A RABBIT MODEL OF MYOCARDIAL-ISCHEMIA AND REPERFUSION

1 This study examined whether endothelin-1 (ET-1) reduces infarct size in a rabbit model of acute coronary artery occlusion (60 min) and reperfusion (120 min). In addition, we investigated whether the observed cardioprotective effect of ET-1 was due to the activation of ATP-sensitive potassium (K-ATP) channels by using two selective antagonists, glibenclamide and sodium 5-hydroxydecanoate (5-HD). 2 In the anaesthetized rabbit, infarct size (expressed as a percentage of the area at risk) after 60 min of coronary artery occlusion followed by 2 h of reperfusion was 55+/-4% (n=11). ET-1 (0.3 nmol kg(-1)), administered as a bolus injection into the left ventricle, had no effect on infarct size (62+/-2%, n=4). A lower dose of ET-1 (0.03 nmol kg(-1)) resulted in a significant reduction in infarct size (infarct size 43+/-3%; P<0.05, n=16). The higher dose (0.3 nmol kg(-1)), but not the lower dose of ET-1 caused a significant rise in blood pressure, pressure rate index and hence, myocardial oxygen consumption. 3 The reduction in infarct size afforded by ET-1 (0.03 nmol kg(-1)) was abolished by pretreatment of rabbits with the K-ATP channel inhibitors, glibenclamide (0.3 mg kg(-1)) and 5-HD (5 mg kg(-1)), (infarct size 59+/-3 and 63+/-4% respectively; n=4-9). 4 We propose that ET-1 reduces infarct size by opening K-ATP channels.