Similarities between ischemic preconditioning and 17β-estradiol mediated cardiomyocyte KATP channel activation leading to cardioprotective and antiarrhythmic effects during ischemia/reperfusion in the intact rabbit heart

The aims of our present work were to assess whether treatment with either ischemic preconditioning (IPC) or 17 beta-estradiol or both combined produce proarrhythmic or antiarrhythmic effects, and whether opening of the sarcolemmal or mitochondrial K-ATP channels is relatable to this effect; to assess biochemically the effects of IPC and/or 17 beta-estradiol oil oxidant stress and antioxidant defenses in the myocardium; to examine the effects of nitric oxide (NO) synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME) pretreatment in rabbits treated with either IPC or 17 beta-estradiol (because 17 beta-estradiol evoked NO release has been implicated in K-ATP activation and IPC); and examine the effects of ischemic preconditioning and 17 beta-estradiol oil myocardial energy metabolism during ischemia and reperfusion in a well-standardized model of reperfusion arrhythmias in anesthetized adult male New Zealand White rabbits (n = 124) subjected to 30 minutes Occlusion of the left coronary artery followed by 120 minutes Of reperfusion . Pretreatment with either 17 beta-estradiol (10 mu g/kg, i.v.) or one cycle of ischemic preconditioning prior to the period of coronary occlusion offers significant infarct size reduction (18.6 +/- 2.2% and 19.4 +/- 1.9%, respectively versus 40.1 +/- 3.9% in saline control and 39.2 +/- 3.2% in vehicle control groups; P < 0.01) and antiarrhythmic effects. Both 17 beta-estradiol and ischemic preconditioning treatment significantly attenuated the incidence of life-threatening arrhythmias like Sustained VT (13% and 13%, respectively versus 100% in saline control and 100% in vehicle control groups; P < 0.001) and other arrhythmias (25% and 25%, respectively versus 100% in saline control and 100% in vehicle control groups; P < 0.001), and were quite effective in increasing the number of animals that survived without developing any arrhythmia during ischemia and reperfusion. 5-hydroxydecanoate(5-HD; 5 mg/kg, i.v) alone offered no cardioprotective and antiarrhythmic activities. Pretreatment with 5-HD but not HMR 1883 (3 mg/kg, i.v.) abolished the beneficial effects of 17 beta-estradiol and ischemia preconditioning oil reperfusion-induced arrhythmias and cardioprotection suggesting that Such effects have been achieved via the selective activation of cardiomyocyte mito-chondrial K-ATP channels rather than sarcolemmal K-ATP channels. The reduced reperfusion arrhythmic incidence and durations induced by estrogen was not significantly altered by ICI 182 720 (2.5 mg/kg, i.v). The lack of effect of ICI 182 720 oil antiarrhythmic and inflarct-limiting effects of 17 beta-estradiol and ischemic preconditioning suggest that these favorable effects are rapid, direct, and non-genomic effects. This Study demonstrates similarities between 17 beta-estradiol and ischemic preconditioning of the rabbit myocardium in terms Of cardioprotection, antiarrhythmic, and rnetabolic activities. Ischemic preconditioning and 17 beta-estradiol appear to share a final common effector; the mitocliondrial K-ATP, channel.