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.