Prevention and abolition of ouabain-induced ventricular tachycardia by potassium canrenoate in dogs

Abstract

It has been shown that spironolactone (Aldactone) protects the rat against myocardial necroses induced by digitoxin (Selye et al., 1969) through the induction of hepatic microsomal enzymes (Solymoss et al., 1969). The present study investigated whether spironolactone (S) and potassium canrenoate (K Can), a newly synthesized specific antagonist of aldosterone, had protective effects against ouabain (OU)-induced ventricular tachycardia (VT) in dogs. After a priming dose of 7.5 μg/kg, OU was infused at a rate of 2 μg/kg i.v. to the following 4 groups of pentobarbital anesthetized dogs until the development of VT: (I) 8 control dogs; (II) 5 dogs pretreated with i.m. S, 5 mg/kg, twice daily for 5 days; (III) 8 dogs receiving a simultaneous infusion of K Can 0.02 mEq/min plus OU; (IV) another 8 dogs receiving a simultaneous potassium chloride (KCl) infusion, also 0.02 mEq/min, plus OU. VT occured at 34±1 min in the control group; 32±1 min in group II, 47±4 min in group III ( p<0.02, compared to groups I, II and IV), and 34±2 min in group IV. VT was converted by 0.5 mEq of K Can to sinus rhythm in 6 of 11 dogs; all conversion took place within 1 min after K Can injection. No conversion of VT was noted either after the administration of equivalent amount of S (8 experiments) or KCl (10 experiments). These data indicate that K Can has potent antiarrhythmic activity in OU toxicity. This antiarrhythmic activity of K Can probably was not related to the potassium ion, and was not mediated by a mechanism related to the induction of drug-metabolizing enzymes in the liver.