Arrhythmogenic and inotropic effects of interferon investigated in perfused and in vivo rat hearts: influences of cardiac hypertrophy and isoproterenol.

Abstract

Although the arrhythmogenic effects of interferon (IF) have been reported in clinical practice, the experimental data are limited. Therefore, these effects were investigated in in vivo and Langendorff-perfusion studies using 3 different groups of rats (ie, control, aorta-banded, and deoxycorticosterone acetate (DOCA)-salt hypertension groups) in the presence or absence of isoproterenol. In the perfusion study, human recombinant IF-alpha (< or =15,000 U/ml) alone induced irreversible atrioventricular blockade in all groups, whereas this agent (< or =1,500 U/ml) caused negative inotropism and ventricular tachyarrhythmias (arrhythmic score greater in the order of DOCA-salt>aorta-banded = control group) in the preparations pretreated with isoproterenol (10(-9) mol/L). In an in vivo study, IF-alpha (6x10(6) U/kg) resulted in ventricular tachyarrhythmias only in the presence of isoproterenol (10 mg/kg), as in the perfusion study (arrhythmic score; DOCA-salt>aorta-banded>control). In conclusion, the arrhythmogenesis of IF-alpha is potentiated in pathophysiological conditions such as cardiac hypertrophy or elevated sympathetic activity.