Electrophysiological effects of verapamil

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Abstract
Previous studies have demonstrated that verapamil possess potent anti-arrhythmic effects. The present study has been designed to define the cardiovascular effects of this drug. Isolated tissue studies performed in rabbit right atrium demonstrated that prompt and prominent slowing of the sinus rate even at a dose of 1 × 10−7 mol·litre−1. This dose produced significant decrease in action potential amplitude and phase 4 slope, shifted the ‘threshold potential’ to a less negative value, prolonged action potential duration but did not change maximum diastolic potential. At this dose of verapamil, sinoatrial conduction time prolonged significantly (control: 40.0± 4.8 ms; 1 × 10−7mollitre−1 verapamil: 50.0± 6.4 ms). Purkinje fibre studies demonstrated decreases in dV/dt, resting potential, total amplitude, action potential duration at 75, 95% of recovery and effective refractory period only after exposure to >1 × 10−5 mol·litre−1 verapamil. Electrophysiological studies in conscious dogs demonstrated, after bolus administration of verapamil, progressive increases in the A–H interval and heart rate, but no changes in H–V and QRS intervals. Anaesthetised dog studies showed the lack of significant effect on A–H and H–V intervals or QRS duration regardless of the bolus dose of verapamil. However, verapamil produced statistically significant increases in heart rate after 0.025 mg·kg−1. Verapamil administration did not produce a statistically significant change in escape pacemaker rate in vagal stimulation experiments or with spontaneously beating isolated Purkinje fibres. Finally, the effect of increasing intravenous bolus doses of verapamil on ischaemic arrhythmias was studied in five conscious dogs 24 h following LAD ligation. Only one dog with ventricular tachycardia and another dog with junctional escape rhythm were converted to sinus rhythm after the 0.05 mg·kg−1 and 0.2 mg·kg−1 doses, respectively. In conclusion, these studies demonstrated that administration of verapamil specifically depresses tissue with electrophysiological dependence on slow channel current. Therefore, sinus and A–V nodal events would be suppressed and slow-channel mediated events in ischaemic ventricle also would be inhibited. Clinically, acute administration of verapamil would lead to depression of sinus and A–V nodal function as well as potentially eliminate slow current mechanisms in ischaemic arrhythmias.