Use of Potassium Canrenoate to Suppress Ouabain-Induced Ventricular Arrhythmias in Dogs

Abstract

Potassium canrenoate, a steroidal compound and a specific antagonist of aldosterone, had (1) a potent protective effect against ouabain-induced ventricular tachycardia in intact closed-chest dogs and (2) a potent antiarrhythmic effect in abolishing ventricular bigeminy and ventricular tachycardia due to ouabain intoxication in dogs. Conversion of ouabain-induced arrhythmias was usually associated with an improvement in atrioventricular conduction, but no significant alterations in blood pressure or myocardial contractility occurred. Equivalent doses of potassium chloride failed to delay the occurrence of or to abolish the ouabain-induced ventricular tachycardia. Therefore, the antiarrhythmic activity of potassium canrenoate does not seem to be related to the potassium ion in the molecule. Since the compound combines both antiarrhythmic and diuretic activity, potassium canrenoate may be a valuable clinical agent for patients on digitalis therapy.KEY WORDS potassium chloride ventricular bigeminy atrioventricular conduction ventricular tachycardia myocardial contractility• Potassium canrenoate or Soldactone (potassium 3-[3-oxo-17/3-hydroxy-4, 6-androstadien-17a-yl]propanoate) is a newly synthesized steroidal compound which specifically inhibits the effects of aldosterone on the renal tubules (personal communication from G. D. Searle & Company). Like spironolactone, it induces diuresis and natriuresis in animals with and without secondary aldosteronism. In contrast to spironolactone, potassium canrenoate has a high water solubility and can be given parenterally. The diuretic and natriuretic potency of potassium canrenoate is comparable to that of the thiazides. At a daily dose of 200-900 mg, clinically beneficial A preliminary report of this work was presented at the 55th Annual Meeting of the Federation of American Societies for Experimental Biology, Chicago, April, 1971 (Fed Proc 30:228, 1971.Address reprint requests to Dr. Yeh, P.O. Box 875, Biscayne Annex, Miami, Florida 33152.Received October 1, 1971. Accepted for publication September 29, 1972. responses have been observed in postoperative patients (1) and in patients with refractory cardiac edema (2). We have discovered that potassium canrenoate, in addition to being a diuretic agent, also has potent antiarrhythmic activity in digitalis toxicity; moreover, this activity is unrelated to the potassium ion in the molecule. The molecular structure of potassium canrenoate is shown in Figure 1. MethodsAdult mongrel dogs weighing 14-20 kg were anesthetized with sodium pentobarbital (30 mg/kg, iv) and maintained with controlled respiration. Arterial blood pressure was recorded through a catheter inserted into a femoral artery and connected to a Statham P23DB transducer. Multiple surface electrocardiograph leads were monitored. Two peripheral veins were cannulated. Recordings from the area of the sinoatrial (SA) node were obtained with an electrode catheter in intact closed-chest dogs and with plunge wires in open-chest dogs. His bundle electrograms were re...

Electrophysiologic Effects of Potassium Canrenoate on Ouabain-Induced Ventricular Dysrhythmias in Rabbits

“…The PR interval did not change after potassium canrenoate administration except in two instances: in one case there was a slight prolonga tion and in the other a shortening. These findings confirm our previous report that in contrast to other antidysrhythmic drugs, such as quinidine (5, 15), pro cainamide (4 -5 ), and propranolol (11), conversion by canrenoate is not associ ated with a depression in cardiac conduction (18). Potassium canrenoate is de scribed as having no negative inotropic effect (6,12,16), but may have a slight positive inotropic action on the myocardium.…”

“…Potassium canrenoate is de scribed as having no negative inotropic effect (6,12,16), but may have a slight positive inotropic action on the myocardium. In the dog heart, no significant alteration of the inotropic effect of ouabain was observed after the conversion of ouabain-induced ventricular tachycardia by canrenoate (18). The latter is inef fective against dysrhythmias due to catecholamines or acute coronary artery ligation in dogs and has no effect on Purkinje fibers damaged by stretch and hypoxia (16,19).…”

“…In dog experiments, the sinus rate may be increased, decreased, or remain unchanged during the conversion of ouabain-induced ventricular tachy cardia (18). Since the sinus rate was not recorded during the ouabain-induced ventricular tachycardia in the work performed by Lucchesi and Haley (7) there is no evidence to support their interpretation that canrenoate conversion is due to overdrive suppression.…”

Inability of Potassium Canrenoate to Convert Experimentally Induced Ouabain Arrhythmias in the Canine Heart

“…Previous studies (1)(2)(3)(4) have suggested that potassium canrenoate is an antagonist to the cardiotoxic actions of ouabain. Supposedly, the drug induces conversion to sinus rhythm in an all or none manner in ouabain-intoxicated dogs.…”

“…• Potassium canrenoate (Soldactone or potassium 3- [3-oxo-17-/3-hydroxy-4, 6, androstadien-17-a-yl]propanoate), a diuretic which specifically antagonizes aldosterone, reportedly can prevent or terminate experimentally-induced digitalis arrhythmias (1)(2)(3)(4). Yeh and Lazarra (3) showed that 5 x 10~5M potassium canrenoate restored resting membrane potential, action potential overshoot, rate of rise of the action potential (dV/dt), and membrane excitability in canine Purkinje fibers poisoned with ouabain.…”