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Circulation, Vol 80, 369-379, Copyright © 1989 by American Heart Association

ARTICLES

Cell calcium in the pathophysiology of ventricular fibrillation and in the pathogenesis of postarrhythmic contractile dysfunction

Y Koretsune and E Marban
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

The mechanism of ventricular fibrillation is poorly understood at the cellular level. We explored the role of intracellular free calcium in the pathophysiology and pathogenesis of ventricular fibrillation in perfused ferret hearts loaded with the Ca2+ indicator 5F-BAPTA. Nuclear magnetic resonance spectroscopy was used to measure [Ca2+]i, pH, and high-energy phosphates. During ventricular fibrillation induced by burst pacing, [Ca2+]i rose rapidly and dramatically, exceeding by four times the control within 5 minutes. [Ca2+]i remained markedly elevated throughout 20 minutes of fibrillation, but it returned to control values shortly after defibrillation. In a group of hearts kept isovolumic by a balloon in the left ventricle, acidosis and high-energy phosphate depletion developed despite the maintenance of normal coronary pressure. To distinguish the effects of superimposed ischemia from those of the arrhythmia itself, we lowered left ventricular volume during fibrillation in a second group of hearts. This maneuver decreased wall stress such that fibrillation had no significant adverse effect on intracellular pH, high-energy phosphates, or lactate efflux. [Ca2+]i still increased remarkably despite the absence of ischemic changes. Developed pressure did not recover to control levels after defibrillation in either group; the hearts appeared "stunned." We conclude that intracellular calcium increases as a direct consequence of ventricular fibrillation. The increase in [Ca2+]i may cause the contractile dysfunction observed in postarrhythmic hearts. Its possible role in initiating or maintaining the arrhythmia is less clear.

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