Simulation Studies of Cyanide-Caused Cardiac Toxicity

Report No. ARL-TR-3443
Authors: C. K. Zoltani, COL G. E. Platoff, and S. I. Baskin
Date/Pages: March 2005; 20 pages
Abstract: A series of computer studies showing the effect of cyanide (CN) on the electrophysiology of cardiac tissue is presented. A mathematical model of the electrophysiology of cardiac tissue, with initial and boundary conditions based on experimental data from studies using CN as metabolic blockers from the literature, was used to simulate changes in the electrical activity of the heart. Emphasis was on the modulation of ion concentrations in the cells, changes in current magnitudes, and the activation of currents that are dormant under normal circumstances. These calculations showed for the first time: (1) disturbance of the energy homeostasis and ion concentrations in cardiac tissue due to CN results in the reversal of the direction from the normal and change in magnitudes of cellular membrane currents. These, in turn, change the morphology of the action potential and the electrocardiogram (ECG). This is the initial step leading to ventricular fibrillation, the usual endpoint in the effect of CN on the heart. (2) CN causes cell swelling and hemorrhaging in cardiac tissue. Cell swelling activates chloride membrane currents affecting homeostasis of the tissue. These effects were shown to be important for the electrical state of the CN-affected tissue and were included for the first time in a model of CN-affected cardiac tissue. (3) The calculations reproduced aspects of the changes in an ECG of a subject under the effect of a lethal dose of CN. (4) The obtained results suggest and define the characteristics required of a pharmacological intervention needed to overcome or reverse CN poisoning, of vital importance for development of therapeutics for force protection. Primarily, such intervention needs to reduce the calcium overload of the cardiac cell, restore the depolarizing sodium current, and alleviate the accumulation of potassium ions exterior to the cell.
Distribution: Approved for public release
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Last Update / Reviewed: March 1, 2005