Effect of drugs on conduction delay and incidence of ventricular arrhythmias induced by acute coronary occlusion in dogs.
The effects of various drugs on delayed activation of the ischemic myocardium and the incidence of ventricular arrhythmias were studied in 34 open-chest anesthetized dogs. The left anterior descending coronary artery was occluded for 6 minutes before and 42 minutes after administration of aprindine (2.85 mg/kg body weight), quinidine (8 mg/kg) and verapamil (0.2 mg/kg) and during infusion of isoproterenol (0.2 microng/min). The time intervals from the onset of the QRS complex to the major deflection of the bipolar electrograms recorded within the normal and ischemic zones were measured at cycle lengths of 500, 400 and 300 msec and were correlated with the development of ventricular arrhythmias. At a cycle length of 500 msec, aprindine increased by 19.5 msec the delay in activation time produced by coronary ligation alone (P less than 0.05), whereas verapamil reduced by 10 msec the extent of ischemia-induced conduction delay (P less than 0.05). The delay in activation time in the ischemic zone was not significantly altered by quinidine or isoproterenol. The incidence of ventricular arrhythmias was increased by aprindine (from 1 in 11 to 8 in 11 dogs), decresed by verapamil (from 3 in 7 to 0 in 7 dogs) and was not changes by quinidine or isoproterenol. Thus, delayed activation of the ischemic myocardium appears to play an important role in the genesis of early arrhythmias due to myocardial ischemia, and drugs that significantly depress conduction in the ischemic myocardium may predispose to the development of ventricular arrhythmia whereas those that improve conduction may be protective. Contrary to their effects on slow channel-dependent conduction, verapamil improved and isoproterenol worsened conduction during ischaemia.
D000818:Animals; D001073:Aprindine / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000209:etiology*; D003327:Coronary Disease / Q000150:complications*; D004195:Disease Models, Animal; D004285:Dogs; D006329:Heart Conduction System / Q000187:drug effects*; D007192:Indenes / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology*; D011802:Quinidine / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
D007192:Indenes; D001073:Aprindine; D014700:Verapamil; D011802:Quinidine; D007545:Isoproterenol