BLOCKADE OF ATP-SENSITIVE POTASSIUM CHANNELS BY 5-HYDROXYDECANOATE SUPPRESSES MONOPHASIC ACTION-POTENTIAL SHORTENING DURING REGIONAL MYOCARDIAL-ISCHEMIA

We tested 5-hydroxydecanoate (5-HD), a specific blocker of ATP-sensiti ve potassium channels (IK.ATP), to determine if it mitigates electroph ysiologic changes produced by regional myocardial ischemia in vivo. A sequence of 5-minute occlusion of the distal LAD and 30-minute reperfu sion was repeated while recording the monophasic action potential (MAP ) and bipolar electrogram (EG) from the epicardial center of the ische mic myocardium in anesthetized dogs. 5-HD (30 mg/kg, IV) or glibenclam ide (0.15 or 0.3 mg/kg kg, IV) was administered before the third occlu sion, and the data were compared to the second occlusion data. 5-HD di d not affect baseline MAP duration at 90% and 50% repolarization (APD9 0, APD50) before LAD occlusion but suppressed occlusion-induced shorte ning of APD90 (16 +/- 2% during the second occlusion vs. 5 +/- 3% duri ng the third occlusion, n = 8, p < 0.01) and APD50 (16 +/- 3% vs. 10 /- 3%, n = 8, p < 0.05). Pretreatment with glibenclamide also suppress ed occlusion-induced MAP shortening and eliminated an additional effec t of 5-HD (n = 3). 5-HD did not affect the occlusion-induced increase in duration and activation time of EG. 5-HD, as well as glibenclamide, suppressed regional ischemia-induced MAP shortening, probably by bloc king activation of IK.ATP, without affecting conduction delay. These d ifferential effects of 5-HD on repolarization and conduction during th e early phase of regional ischemia might have the potential to suppres s reentrant ventricular arrhythmias.