Extraordinary potentiation of isoproterenol cardiotoxicity by corticoid pretreatment

Abstract

In albino rats, chronically pretreated with desoxycorticosterone acetate (DCA) and saline, the cardiotoxicity of the β-adrenergic agonist, isoproterenol, was enormously potentiated (about 20,000 times!). In such animals, a small dose of isoproterenol (6 (μg per 100 g body weight) which otherwise does not produce any irregularities of cardiac rhythm, consistently induced severe arrhythmias, usually leading to ventricular fibrillation and death. Following the same pretreatment, the α- and β-adrenergic agonist, epinephrine, elicited arrhythmias and ventricular fibrillation less consistently and only in the presence of α-adrenergic receptor blockade. Hydrocortisone was less effective than DCA in sensitizing the myocardium to isoproterenol. Substantial enhancement of isoproterenol cardiotoxicity was demonstrated also in the guinea pig pretreated with DCA and saline. The possibility of a potentially lethal drug-drug interaction in patients on prolonged corticoid therapy receiving large dosages of isoproterenol or other β-adrenergic agonists is considered.