Research

ISCHEMIA AND SODIUM OVERLOAD

Brief Summary of Publications (for full text, click on titles)

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Gima, K. and Y. Rudy (2002). "Ionic current basis of electrocardiographic waveforms: a model study." Circ Res 90(8): 889-96.

Body surface electrocardiograms and electrograms recorded from the surfaces of the heart are the basis for diagnosis and treatment of cardiac electrophysiological disorders and arrhythmias. Given recent advances in understanding the molecular mechanisms of arrhythmia, it is important to relate these electrocardiographic waveforms to cellular electrophysiological processes. This modeling study establishes the principles that provide a mechanistic cellular basis for interpretation of electrocardiographic waveforms.

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We investigate effects of elevated intracellular sodium on the cardiac action potential (AP) and on intracellular calcium using the Luo-Rudy model of a mammalian ventricular myocyte. By slowing AP depolarization (hence velocity) and shortening APD, Na+-overload acts to enhance inducibility of reentrant arrhythmias. Shortened APD with elevated [Ca2+]i (secondary to Na+-overload) also predisposes the myocardium to arrhythmogenic delayed afterdepolarizations.

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Shaw, R. M. and Y. Rudy (1997). "Electrophysiologic effects of acute myocardial ischemia. A mechanistic investigation of action potential conduction and conduction failure." Circ Res 80(1): 124-38.

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. 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.

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Shaw, R. M. and Y. Rudy (1997). "Electrophysiologic effects of acute myocardial ischemia: a theoretical study of altered cell excitability and action potential duration." Cardiovasc Res 35(2): 256-72.

To study the ionic mechanisms of electrophysiologic changes in cell excitability and action potential duration during the acute phase of myocardial ischemia. Using an ionic-based theoretical model of the cardiac ventricular cell, the dynamic LRd model, we have simulated the three major component conditions of acute ischemia (elevated [K]o, acidosis and anoxia) at the level of individual ionic currents and ionic concentrations. The conditions were applied individually and in combination to identify ionic mechanisms responsible for reduced excitability at rest potentials, delayed recovery of excitability, and shortened action potential duration.

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