title: 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.
authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Odashiro
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Hiramatsu
authors.forename: Nobuhito
authors.initials: N
authors.lastname: Yanagi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Arita
authors.forename: Toru
authors.initials: T
authors.lastname: Maruyama
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kaji
authors.forename: Mine
authors.initials: M
authors.lastname: Harada
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology*; D006332:Cardiomegaly / Q000150:complications*; D004357:Drug Synergism; D006327:Heart Block / Q000139:chemically induced; D006801:Humans; D066298:In Vitro Techniques; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D012016:Reference Values; D013566:Sympathomimetics / Q000494:pharmacology*; D017180:Tachycardia, Ventricular / Q000139:chemically induced
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D013566:Sympathomimetics; D007545:Isoproterenol