(Circulation. 1997;95:1937-1944.)
© 1997 American Heart Association, Inc.
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Unanticipated Lessening of the Rise in Extracellular Potassium During Ischemia by Pinacidil
From the Experimental Cardiology Group, Cardiology Division, Department of Medicine (A.K., I.W., M.L.W., C.L.E., L.S.G.), and the Department of Biostatistics, School of Public Health (S.L., G.C.K.), University of North Carolina at Chapel Hill.
Correspondence to Leonard S. Gettes, MD, UNC School of Medicine, CB #7075, 349 Burnett-Womack Bldg, Chapel Hill, NC 27599-7075. E-mail lsgettes{at}vmax.card.unc.edu
Background The efflux of potassium (K) through the ATP- sensitive K channel is considered an important cause of the rise in extracellular K ([K+]e ) during no-flow ischemia. We postulated that agents that enhance K conductance in this channel would enhance the rise in [K+]e.
Methods and Results We studied the effects of 10 and 25 µmol/L pinacidil, an ATP-sensitive K channel opener that provides metabolic protection to the ischemic myocardium, on the rise in [K+]e recorded by K-sensitive electrodes, the change in action potential duration (APD) recorded by microelectrodes, and the changes in activation during ischemia in in situ pig hearts and Tyrode-perfused rabbit interventricular septa. Pinacidil 25 µmol/L unexpectedly lessened the rise in [K+]e and the activation delay in both preparations. Pinacidil 10 µmol/L had no effect in the rabbit and only a slight effect in the pig. Both concentrations significantly exaggerated the APD shortening induced by ischemia. By varying stimulation frequency, we demonstrated that the rise in [K+]e during ischemia, both before and after pinacidil, correlated with the time that the action potential was at its plateau voltage.
Conclusions Our results indicate that the rise in [K+]e during ischemia is due to multiple factors, including K conductance across membrane channels, K driving force as reflected by the time 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 pinacidil reflects the balance of its effects on these several parameters.
Key Words: potassium • pinacidil • ischemia • action potentials • electrophysiology
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