Intracellular Ca dynamics in ventricular fibrillation

Chikaya Omichi, Scott T. Lamp, Shien-Fong Lin, Junzhong Yang, Ali Baher, Shengmei Zhou, Mina Attin, Moon Hyoung Lee, Hrayr S. Karagueuzian, Boris Kogan, Zhilin Qu, Alan Garfinkel, Peng Sheng Chen, James N. Weiss*

*Corresponding author for this work

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

In the heart, membrane voltage (Vm) and intracellular Ca (Cai) are bidirectionally coupled, 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, sarcoplasmic reticulum Cai cycling may exhibit intrinsic dynamics. Non-voltage-gated Cai 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 Cai is associated with V m during VF. Cai 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 (Vm) 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). Cai 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, 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. 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.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume286
Issue number5 55-5
DOIs
StatePublished - 1 May 2004

Keywords

  • Action potential
  • Calcium transient
  • Cardiac restitution
  • Optical mapping

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    Omichi, C., Lamp, S. T., Lin, S-F., Yang, J., Baher, A., Zhou, S., Attin, M., Lee, M. H., Karagueuzian, H. S., Kogan, B., Qu, Z., Garfinkel, A., Chen, P. S., & Weiss, J. N. (2004). Intracellular Ca dynamics in ventricular fibrillation. American Journal of Physiology - Heart and Circulatory Physiology, 286(5 55-5). https://doi.org/10.1152/ajpheart.00123.2003