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Mechanistic investigation of extracellular K+ accumulation during acute myocardial ischemia: a simulation study.

B Rodriguez‚ JM Jr Ferrero and B Trenor

Abstract

In this study, we have used computer simulations to study the mechanisms of extracellular K+ accumulation during acute ischemia. A modified version of the Luo-Rudy phase II action potential model was used to simulate the electrical behavior of one ventricular myocyte during 14 min of simulated ischemia. Our results show the following: 1) only the integrated effect of activation of ATP-dependent K+ current, an ischemic Na+ inward current, and inhibition of Na(+)-K(+) pump activity in the absence of coronary flow replicates the biphasic time course of extracellular K+ concentration observed during acute ischemia; 2) the time to onset of the plateau phase and the plateau level value are determined by the rate of stimulation and by the rate of alteration of the three mechanisms. However, acidosis and reduction of extracellular volume produce only a slight anticipation of the plateau phase; and 3) cellular K+ loss is mainly due to an increase of K+ efflux via the time-independent K+ current and ATP-dependent K+ current rather than to a decrease of K+ influx.

Details

Journal

American Journal of Physiology−Heart and Circulatory Physiology

Keywords

Acidosis Acute Disease Adenosine Triphosphate Computer Simulation Electric Conductivity Extracellular Space Heart Rate Humans Models‚ Cardiovascular Myocardial Ischemia Potassium Potassium Channels

Number

2

Pages

H490−H500

Publisher

Am Physiological Soc

Volume

283

Year

2002

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