Nicorandil improves ischemic changes on epicardial ECG during short-term coronary occlusion by opening ATP-sensitive potassium channels in pigs

The aims of this study were to investigate whether nicorandil (NIC), an ATP-sensitive potassium channel(KATP) opener and nitrate, has antiischemic effects during transient ischemia in pigs, and to investigate whether its effects are due to Its K-ATP-opening action or nitrate action. Myocardial ischemia was induced by ligating the proximal portion of the left anterior descending coronary artery for 1 minute in anesthetized open-chest pigs, and was measured as the magnitude of ST-segment elevation on epicardial electrocardiogram (ECG). Epicardial ST-segment elevation during coronary occlusion was significantly reduced by pretreatment with NIC (3 mg, intracoronary [ic]), but not by pretreatment with nitroglycerin (NTG, 0.2 mg, ic). Pretreatment with glibenclamide (GLB, a KATP blocker, 6 mg, ic) significantly augmented the ST-segment elevation during coronary occlusion. The augmentation of ST-segment elevation by GLB was significantly reduced by subsequent administration of NIC, but not by that of NTG (0.2 mg, ic). There were no significant differences between hemodynamic variables immediately before coronary occlusion with and without pretreatment. The intracoronary administration of NIC (3 mg) significantly shortened the endocardial monophasic action potential durations at 50% (MAPD50) and 90% repolarization (MAPD90) by 28.3 +/- 6.9% and 17.0 +/- 4.7%, respectively. These results suggest that the intracoronary administration of NIC has antiischemic effects during transient ischemia via KATP activation in myocardium.