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...
