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1 Department of Medicine, physiology, UCLA Cardiovascular Research Laboratory, Los Angeles, CA, USA
2 Division of Cardiology, Cedars-Sinai Medical Center and Center for Health Sciences, UCLA Cardiovascular Research Laboratory, Los Angeles, CA, USA
3 Physiological Science and Computer Science, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
* To whom correspondence should be addressed. E-mail: jweiss{at}mednet.ucla.edu.
Background- In heart, membrane voltage (Vm) and intracellular Ca (Cai) are bidirectionallycoupled, so that ionic membrane currents regulate Cai cycling and Cai affects ionic currents regulating action potential duration (APD). Although Cai reliably and consistently tracks Vm at normal heart rates, it is possible that at very rapid rates, SR Cai cycling may exhibit intrinsic dynamics. Non-voltage gated Cai release might cause local alternations in APD and refractoriness which influence wavebreak during ventricular fibrillation (VF). In this study we tested this hypothesis by examining the extent to which Cai is associated with Vm during VF. Methods- Cai transients were mapped optically in isolated arterially-perfused swine right ventricles (RVs) using the fluorescent dye Rhod-2-AM, while simultaneously recording intracellular membrane potential either locally with a microelectrode (5 preparations) or globally with the voltage sensitive dye RH-237 (5 preparations). Results- Mutual information (MI) is a quantitative statistical measure of the extent to which knowledge of one variable (Vm) predicts the value of a second variable (Cai). MI was high during pacing and VT (1.13±0.21 and 1.69±0.18, respectively), but fell dramatically during VF (0.28±0.06, p<0.001). Cai at sites 4- 6 mm apart also showed decreased MI during VF (0.63±0.13) compared to pacing (1.59±0.34, p<0.001) or VT (2.05±0.67, p<0.001). Spatially, Cai 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 Vm and Cai signals analyzed by fast Fourier transform were similar during VT but differed significantly during VF. Conclusions- Cai is closely associated with Vm closely during pacing and VT, but not during VF. These findings suggest that during VF, non voltage-gated Cai release events occur, and may influence wavebreak by altering Vm and APD locally.
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