Arrhythmogenic and inotropic effects of interferon investigated in perfused and in vivo rat hearts: influences of cardiac hypertrophy and isoproterenol.
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.
Odashiro
Keita
K
Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Hiramatsu
Shin-ichi
S
Yanagi
Nobuhito
N
Arita
Takeshi
T
Maruyama
Toru
T
Kaji
Yoshikazu
Y
Harada
Mine
M
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
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D013566:Sympathomimetics; D007545:Isoproterenol