title: Modulation of ventricular fibrillation in the isolated heart: the role of slow calcium channel activity under continuous perfusion.
abstract: The individual activities of sodium versus calcium channels in the initiation and maintenance of ventricular fibrillation (VF) have not been fully elucidated. Therefore we studied in isolated heart under nonischemic conditions (a) VF characteristics in untreated hearts, (b) initiation and maintenance of VF during attenuation and blockade of slow calcium channel activity by verapamil, (c) the effect of these interventions on the characteristics of the induced arrhythmia, and (d) the impact of heart weight on the observed results. Measurements were carried out in both ventricles of isolated feline hearts during ventricular pacing and 8 min of electrically induced tachyarrhythmias. Measurements during ventricular pacing included epicardial conduction time (CON), refractoriness (VRP), and all tissue resistivity (ATR; an indirect measure of changes in intercellular electrical coupling). Measurements during arrhythmia included ATR, peak frequency [PKF; a measure of the prevailing frequency based on Fast Fourier Transform (FFT) analysis], and normalized entropy (ENTROP; a measure of the degree of arrhythmia organization). Measurements during sinus rhythm and arrhythmia were repeated after blocking of calcium channel activity by verapamil at a high concentration (1.8x10(-4) M; n = 8) and at two low concentrations (1.5 and 3.0x10(-7) M; n = 8). In untreated hearts, mainly VF episodes were induced, exhibiting a low degree of organization with no significant change in this parameter throughout the arrhythmia (8 min). In the left ventricle (LV; and to a much smaller extent in the right ventricle; RV), a gradual increase in PKF was observed throughout the arrhythmia, with no significant change in ATR. Verapamil at a high concentration increased CON, but did not affect VRP. These findings were similar in both ventricles. In lower verapamil concentrations, CON was not affected, and VRP was slightly shortened. After treatment with a high verapamil concentration, VF could not be induced in small hearts but was always inducible in large hearts. Transient arrhythmia episodes appeared in 9% of untreated hearts, in 25% with "high" verapamil, and in 25-37% with "low" verapamil. With all verapamil concentrations, the induced arrhythmia was modulated from a predominantly VF to PVT or MVT type, manifested by a decrease in ENTROP. This effect was less pronounced with increasing heart weight. No significant change in PKF and in ATR was obtained with verapamil throughout the arrhythmia. It is suggested that verapamil modulation of arrhythmia organization is associated mainly with a direct blockade of calcium channel activity (perhaps by causing reduction in the safety factor for conduction), rather than with indirect modulation of electrophysiological parameters.
authors.affiliation: Neufeld Cardiac Research Institute, Sackler School of Medicine, Tel Aviv University, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Amitzur
authors.forename: V
authors.initials: V
authors.lastname: Pogatz
authors.forename: I
authors.initials: I
authors.lastname: Novikov
authors.forename: E
authors.initials: E
authors.lastname: Kaplinsky
authors.forename: M
authors.initials: M
authors.lastname: Eldar
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002415:Cats; D004558:Electric Stimulation; D004594:Electrophysiology; D005260:Female; D005583:Fourier Analysis; D006321:Heart / Q000503:physiopathology*; D006329:Heart Conduction System / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects / Q000502:physiology; D010477:Perfusion; D012032:Refractory Period, Electrophysiological / Q000187:drug effects / Q000502:physiology; D013610:Tachycardia / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000473:pathology / Q000503:physiopathology*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014700:Verapamil