UNANTICIPATED LESSENING OF THE RISE IN EXTRACELLULAR POTASSIUM DURINGISCHEMIA BY PINACIDIL

Background The efflux of potassium (K) through the ATP-sensitive K cha nnel is considered an important cause of the rise in extracellular K ( [K+](e)) during no-flow ischemia. We postulated that agents that enhan ce K conductance in this channel would enhance the rise in [K+](e). Me thods and Results We studied the effects of 10 and 25 mu mol/L pinacid il, an ATP-sensitive K channel opener that provides metabolic protecti on to the ischemic myocardium, on the rise in [K+](e) recorded by K-se nsitive electrodes, the change in action potential duration (APD) reco rded by microelectrodes, and the changes in activation during ischemia in in situ pig hearts and Tyrode-perfused rabbit interventricular sep ta. Pinacidil 25 mu mol/L unexpectedly lessened the rise in [K+](e) an d the activation delay in both preparations. Pinacidil 10 mu mol/L had no effect in the rabbit and only a slight effect in the pig. Both con centrations significantly exaggerated the APD short shortening induced by ischemia. By varying stimulation frequency, we demonstrated that t he rise in [K+](e) during ischemia, both before and after pinacidil, c orrelated with the time that the action potential was at its plateau v oltage. Conclusions Our results indicate that the rise in [K+](e) duri ng ischemia is due to multiple factors, including K conductance across membrane channels, K driving force as reflected by the rime that the action potential is at its plateau voltage, and the metabolic effects of ischemia. The unanticipated lessening of the rise in [K+](e) by pin acidil reflects the balance of its effects on these several parameters .