The purpose of the study was to determine whether a newKATP channel opener, Y 26763 (Y), can influence theelectrophysiological properties in the ischemic myocardium as well as todetermine whether the blunting effect of the α1-adrenoceptorantagonist bunazosin (BN) on an ischemia-induced shortening of repolarizationtime can be related to the KATP channel activity. The anteriordescending branch of the left coronary artery was ligated four times for 5minutes, separated by 15 minutes of reperfusion (stages 1–4) to testthe dose-dependent effect of drugs on repolarization. Dogs received eithervehicle (n = 9), Y (0.4, 2.0, and 4.0 μg/kg at stages 2, 3, and 4,respectively, with 0.4 μg/kg/min drip infusion at each of stages2–4, n = 7), BN (0.1 mg at each of stages 2–4, n =8), or a combination of these two drugs (BN + Y, the same dose of BNand Y in groups BN and Y, respectively, n = 9). Drugs wereadministered into the left atrium. The monophasic action potential (MAP)and regional electrograms were recorded. The MAP90 and theduration of the slow deflections (DSD) of the regional electrogram were usedas markers of repolarization. The Vmax of the MAP and the rapiddeflections (DRD) of the regional electrogram were used as markers ofconduction. Y augmented an ischemia-induced shortening of MAP90and DSD in proportion to an increase in the dose given and the plasmaconcentration (P < .05–.01), especially at the epicardialsite. BN and BN + Y blunted the ischemia-related shortening ofMAP90 and DSD, causing a reduction in repolarization timedispersion between the ischemic and normal zones. There were no significantchanges in the Vmax or DRD in the ischemic zone between periodsbefore and after an increase in each drug dose in the four groups. None ofthe seven dogs developed ventricular tachycardia (VT)/ventricularfibrillation (VF) in the Y group, whereas two of the eight dogs in theBN group, three of the nine dogs in the BN + Y group, and three ofthe nine dogs in the control group developed VT/VF. These results suggestthat the α1-adrenergic blocker bunazosin blunts theshortening effect of KATP channel activator on repolarizationtime, and that the KATP channel opener Y may be antiarrhythmic,although the repolarization time dispersion during myocardial ischemia isincreased.