© 1997 American Heart Association, Inc.
Articles |
Electrophysiologic Effects of Acute Myocardial Ischemia
A Mechanistic Investigation of Action Potential Conduction and Conduction Failure
the Cardiac Bioelectricity Research and Training Center, Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.
A multicellular ventricular fiber model was used to determine mechanisms of slowed conduction and conduction failure during acute ischemia. We simulated the three major pathophysiological component conditions of acute ischemia: elevated [K+]o, acidosis, and anoxia. Elevated [K+]o was the major determinant of conduction, causing supernormal conduction, depressed conduction, and conduction block as [K+]o was gradually increased from 4.5 to 14.4 mmol/L. Only elevated [K+]o caused conduction failure when varied within the range reported for acute ischemia. Before block, depressed upstrokes consisted of two distinct components: the first to the fast Na+ current (INa) and the second to the L-type Ca2+ current (ICa(L)). Even in highly depressed conduction, excitability was maintained by INa, with conduction block occurring at 95% INa inactivation. However, because ICa(L) supported the later phase of the depressed upstroke, ICa(L) enhanced conduction and delayed block by increasing the electrotonic source current. At [K+]o=18 mmol/L, slow action potentials generated by ICa(L) were obtained with 10% ICa(L) augmentation. However, in the presence of acidosis and anoxia, significantly larger (120%) ICa(L) augmentation was required. The depressant effect was due mostly to anoxic activation of outward ATP-sensitive K+ current, which counteracts inward ICa(L) and, by lowering the action potential amplitude, decreases the electrotonic current available to depolarize downstream cells. The simulations highlight the interactive nature of electrophysiological ischemic changes during propagation and demonstrate that both membrane changes and load factors (by downstream fiber) must be considered.
Key Words: myocardial ischemia • hyperkalemia • acidosis • anoxia • supernormal conduction • conduction failure
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