MECHANISM OF ACTION OF VERAPAMIL ON SINUS AND AV-NODES

The mechanism of action of verapamil upon the sinus and AV nodes was investigated. Concurrent changes in left circumflex coronary flow, contractile force, ECG (lead II) and blood pressure were recorded in chloralosed artificially respired mongrel dogs. Intra-arterial verapamil decreased the voltage of the P wave with subsequent development of a nodal rhythm and progressive depression of AV conduction without associated changes in coronary flow, contractile force or blood pressure. Pretreatment with verapamil effectively antagonized sinus arrest and atrial fibrillation produced by intra-arterial acetylcholine. Stimulation of the vagus nerve produced cardiac slowing, atrial fibrillation, marked decrease in coronary flow, contractile force and blood pressure with subsequent temporary cardiac arrest. Repeated stimulation after verapamil could not reproduce these changes for long periods. It is concluded that the mechanism of action of verapamil on the sinus and AV nodes involve a direct cardiac effect as well as an antagonism of vagal mechanisms. © 1969.