Opioid-induced cardioprotection against myocardial infarction and arrhythmias: Mitochondrial versus sarcolemmal ATP-sensitive potassium channels

We examined the role of the sarcolemmal and mitochondrial ATP-sensitive pot assium (K-ATP) channel in a rat model of myocardial infarction after stimul ation with the selective delta(1)-opioid receptor agonist TAN-67. Hearts we re subjected to 30 min of regional ischemia and 2 h of reperfusion. Infarct size was expressed as a percentage of the area at risk. TAN-67 significant ly reduced infarct size/area at risk (29.6 +/- 3.3) versus control (63.1 +/ - 2.3). The sarcolemmal-selective K-ATP channel antagonist HMR 1098, admini stered 10 min before TAN-67, did not significantly attenuate cardioprotecti on (26.0 +/- 7.3) at a dose (3 mg/kg) that had no effect in the absence of TAN-67 (56.3 +/- 4.3). Pretreatment with the mitochondrial selective antago nist 5-hydroxydecanoic acid (5-HD) 5 min before the 30-min occlusion comple tely abolished TAN- 67-induced cardioprotection (54.3 +/- 2.7), but had no effect in the absence of TAN-67 (62.6 +/- 4.1), suggesting the involvement of the mitochondrial K-ATP channel. Additionally, we examined the antiarrhy thmic effects of TAN-67 in the presence or absence of 5-HD and HMR 1098 dur ing 30 min of ischemia. Control animals had an average arrhythmia score of 10.40 +/- 2.41. TAN-67 significantly reduced the arrhythmia score during 30 min of ischemia (2.38 +/- 0.85). 5-HD and HMR 1098 in the absence of TAN-6 7 produced an insignificant decrease in the arrhythmia score (8.80 +/- 2.56 and 4.20 +/- 1.07, respectively). 5-HD administration before TAN-67 treatm ent abolished its antiarrhythmic effect (4.71 +/- 1.11). However, HMR 1098 did not abolish TAN-67-induced protection against arrhythmias (1.67 +/- 0.8 0). These data suggest that delta(1)-opioid receptor stimulation is cardiop rotective against myocardial ischemia and sublethal arrhythmias and suggest a role for the mitochondrial K-ATP channel in mediating these cardioprotec tive effects.