Shortening of Action Potential Duration is not Prerequisite for Cardiac Protection by Ischemic Preconditioning or a KATPChannel Opener

Abstract Our purpose was to determine whether amelioration of myocardial contractile dysfunction by an ATP-sensitive potassium (K ATP ) channel opener or ischemic preconditioning is mediated by shortening of action potential duration during the early period of ischemia. Extracellular potassium concentration ([K + ] e ), monophasic action potential duration (MAPD) and thickening fraction were measured during ischemia and reperfusion of the left anterior descending coronary artery in anesthetized dogs. Control dogs were subjected to a 10-min occlusion (test occlusion) followed by a 120-min reperfusion. The five dogs, which made up the pinacidil group, received 0.03 mg/kg as an i.v. bolus and then were infused at a rate of 0.04 mg/kg/h for 20 min prior to the test occlusion. In the preconditioning group, six dogs were subjected to a 5-min occlusion and a 10-min reperfusion prior to the test occlusion and reperfusion. Both pinacidil and preconditioning improved regional contraction during reperfusion after the test occlusion. In the control group, MAPD shortened and [K + ] e increased during ischemia. Preconditioning abolished MAPD shortening and blunted the rise of [K + ] e during ischemia. Pinacidil did not affect either the shortening of MAPD or [K + ] e elevation during ischemia. These results suggest that the shortening of MAPD is not a prerequisite for amelioration of contractile dysfunction by a K ATP channel opener or ischemic preconditioning.