title: Intracellular Ca dynamics in ventricular fibrillation.
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 Vm 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 (Cai). 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.
authors.affiliation: Division of Cardiology, Cedars-Sinai Medical Center and Center for Health Sciences, University of California-Los Angeles Cardiovascular Research Laboratory, David Geffen School of Medicine, UCLA, Los Angeles, California 90095-1760, USA.
authors.forename: Chikaya
authors.initials: C
authors.lastname: Omichi
authors.forename: Scott T
authors.initials: ST
authors.lastname: Lamp
authors.forename: Shien-Fong
authors.initials: SF
authors.lastname: Lin
authors.forename: Junzhong
authors.initials: J
authors.lastname: Yang
authors.forename: Ali
authors.initials: A
authors.lastname: Baher
authors.forename: Shengmei
authors.initials: S
authors.lastname: Zhou
authors.forename: Mina
authors.initials: M
authors.lastname: Attin
authors.forename: Moon-Hyoung
authors.initials: MH
authors.lastname: Lee
authors.forename: Hrayr S
authors.initials: HS
authors.lastname: Karagueuzian
authors.forename: Boris
authors.initials: B
authors.lastname: Kogan
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Qu
authors.forename: Alan
authors.initials: A
authors.lastname: Garfinkel
authors.forename: Peng-Sheng
authors.initials: PS
authors.lastname: Chen
authors.forename: James N
authors.initials: JN
authors.lastname: Weiss
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002304:Cardiac Pacing, Artificial; D004594:Electrophysiology; D005260:Female; D005456:Fluorescent Dyes; D005583:Fourier Analysis; D006575:Heterocyclic Compounds, 3-Ring; D007425:Intracellular Membranes / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D008955:Models, Cardiovascular; D011726:Pyridinium Compounds; D013552:Swine; D017180:Tachycardia, Ventricular / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D005456:Fluorescent Dyes; D006575:Heterocyclic Compounds, 3-Ring; D011726:Pyridinium Compounds; C068483:rhod-2; C048153:4-(6-(4-dibutylaminophenyl)-1,3,5-hexatrienyl)-1-(4'-sulfobutyl)pyridinium; D002118:Calcium