Neuromuscular and electrocardiographic responses to verapamil in dogs

Because severe muscular weakness was noted in animals receiving verapamil in doses exceeding those used in humans, we studied the effects of verapamil on neuromuscular function and its correlation with myocardial conduction. The flexor carpi radialis and its nerves were surgically exposed in mechanically ventilated dogs during pentobarbital anesthesia. Indirect and direct electrical stimulation was applied and twitch height recorded following the intravenous administration of verapamil. Twenty animals received one of four dose schedules. The results showed a significant dose-related depression of twitch height to indirect stimulation. Twitch height to direct stimulation was reduced only with the highest dose. The onset of depression of indirect stimulation was temporally associated with onset of A-V conduction delay. However, recovery following indirect stimulation lagged behind recovery of the ECG by 30 min. Recovery times of twitch height following indirect stimulation ranged from 60-208 min and also were dose-related. The qualitative similarity of pancuronium and verapamil on indirect twitch height suggests a similar site of action, i.e., the neuromuscular junction. A presynaptic or postsynaptic effect of verapamil could not be discerned in this study. Verapamil may produce an unrecognized source of weakness in the anesthetized patient either alone or through interaction with anesthetic agents or adjuncts.