Absence of slow channel-dependent conduction within the His-Purkinje (bundle branch) reentrant circuit: A clinical and experimental study of the effects of verapamil

The effects of intravenous verapamil on intraventricular conduction and reentry within the His-Purkinje system were studied in 10 patients and 8 dogs using His bundle electrograms and the ventricular extrastimulus method. In the clinical study, ventricular stimulation was performed by applying stimuli of two times diastolic threshold current strength and in the dog study by applying stimuli ranging in strength from two times diastolic threshold strength to 40 mA. In the clinical study, verapamil was given intravenously as a bolus injection (0.075 to 0.15 mg/kg body weight) and in the dog study as a rapid infusion (0.7 to 1 mg/kg) over 10 minutes followed by continuous infusion at a rate of 0.014 mg/kg per min. Plasma verapamil concentrations ranged from 91 to 173 ng/ml (mean ± standard deviation 138 ± 27) in the clinical study and from 103 to 638 ng/ml (mean 459 ± 174) in the dog study. In both studies, verapamil produced no change in latency and intramyocardial (duration of QRS complex) and His-Purkinje (V₂-H₂ interval) conduction of even the earliest premature impulses delivered before the repolarization of the His-Purkinje system or ventricular muscle, or both, was completed; that is, some fibers might have been at the level of membrane potential at which conduction becomes wholly or in part dependent on the current flowing through the slow channel. Verapamil did not change significantly the determinants of reentry and did not abolish or modify the zone of reentry in any of the 10 patients. These results show that in patients with normal intraventricular conduction, slow channel-dependent conduction plays no role in the propagation of even the earliest premature impulses through the His-Purkinje reentrant circuit. In the absence of any evidence of slow channel-de-pendent conduction, one must assume that the slow propagation of very early premature impulses was mediated by incompletely reactivated rapid inward current system. These observations suggest that the system responsible for slow conduction cannot be recognized from the magnitude of conduction delay.