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Intracellular Ca dynamics in ventricular fibrillation

Division of Cardiology, Cedars-Sinai Medical Center and Center for Health Sciences, University of California-Los Angeles (UCLA) Cardiovascular Research Laboratory, Departments of Medicine, Physiology, Physiological Science, and Computer Science, David Geffen School of Medicine, UCLA, Los Angeles, California 90095

Submitted 13 February 2003 ; accepted in final form 16 December 2003

In the heart, membrane voltage (V_m) and intracellular Ca (Ca_i) are bidirectionally coupled, so that ionic membrane currents regulate Ca_i cycling and Ca_i affects ionic currents regulating action potential duration (APD). Although Ca_i reliably and consistently tracks V_m at normal heart rates, it is possible that at very rapid rates, sarcoplasmic reticulum Ca_i cycling may exhibit intrinsic dynamics. Non-voltage-gated Ca_i release might cause local alternations in APD and refractoriness that influence wavebreak during ventricular fibrillation (VF). In this study, we tested this hypothesis by examining the extent to which Ca_i is associated with V_m during VF. Ca_i transients were mapped optically in isolated arterially perfused swine right ventricles using the fluorescent dye rhod 2 AM while intracellular membrane potential was simultaneously recorded either locally with a microelectrode (5 preparations) or globally with the voltage-sensitive dye RH-237 (5 preparations). Mutual information (MI) is a quantitative statistical measure of the extent to which knowledge of one variable (V_m) predicts the value of a second variable (Ca_i). MI was high during pacing and ventricular tachycardia (VT; 1.13 ± 0.21 and 1.69 ± 0.18, respectively) but fell dramatically during VF (0.28 ± 0.06, P < 0.001). Ca_i at sites 4–6 mm apart also showed decreased MI during VF (0.63 ± 0.13) compared with pacing (1.59 ± 0.34, P < 0.001) or VT (2.05 ± 0.67, P < 0.001). Spatially, Ca_i waves usually bore no relationship to membrane depolarization waves during nonreentrant fractionated waves typical of VF, whereas they tracked each other closely during pacing and VT. The dominant frequencies of V_m and Ca_i signals analyzed by fast Fourier transform were similar during VT but differed significantly during VF. Ca_i is closely associated with V_m closely during pacing and VT but not during VF. These findings suggest that during VF, non-voltage-gated Ca_i release events occur and may influence wavebreak by altering V_m and APD locally.

calcium transient; action potential; cardiac restitution; optical mapping

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