Attenuation of KATP channel-opener induced shortening of repolarization time by alpha 1-adrenoceptor antagonist during ischemia in canine heart

The purpose of the study was to determine whether a new K-ATP channel opene r, Y 26763 (Y), can influence the electrophysiological properties in the is chemic myocardium as well as to determine whether the blunting effect of th e alpha(1)-adrenoceptor antagonist bunazosin (BN) on an ischemia-induced sh ortening of repolarization time can be related to the K-ATP channel activit y. The anterior descending branch of the left coronary artery was ligated f our times for 5 minutes, separated by 15 minutes of reperfusion (stages 1-4 ) to test the dose-dependent effect of drugs on repolarization. Dogs receiv ed either vehicle (n = 9), Y (0.4, 2.0, and 4.0 mu g/kg at stages 2, 3, and 4, respectively, with 0.4 mu g/kg/min drip infusion at each of stages 2-4, n = 7), BN (0.1 mg at each of stages 2-4, n = 8), or a combination of thes e two drugs (BN + Y, the same dose of BN and Y in groups BN and Y, respecti vely, n = 9). Drugs were administered into the left atrium. The monophasic action potential (MAP) and regional electrograms were recorded. The MAP(90) and the duration of the slow deflections (DSD) of the regional electrogram were used as markers of repolarization. The V-max of the MAP and the rapid deflections (DRD) of the regional electrogram were used as markers of cond uction. Y augmented an ischemia-induced shortening of MAP(90) and DSD in pr oportion to an increase in the dose given and the plasma concentration (P < .05-.01), especially at the epicardial site. BN and BN + Y blunted the isc hemia-related shortening of MAP(90) and DSD, causing a reduction in repolar ization time dispersion between the ischemic and normal zones. There were n o significant changes in the V-max or DRD in the ischemic zone between peri ods before and after an increase in each drug dose in the four groups. None of the seven dogs developed ventricular tachycardia (VT)/ventricular fibri llation (VF) in the Y group, whereas two of the eight dogs in the BN group, three of the nine dogs in the BN + Y group, and three of the nine dogs in the control group developed VT/VF. These results suggest that the alpha(1)- adrenergic blocker bunazosin blunts the shortening effect of K-ATP channel activator on repolarization time, and that the K-ATP channel opener Y may b e antiarrhythmic, although the repolarization time dispersion during myocar dial ischemia is increased.