Key result
Interferon-alpha induced ventricular tachyarrhythmias and atrioventricular blockade in rat hearts, with arrhythmogenesis significantly potentiated by cardiac hypertrophy and isoproterenol pretreatment.
Why the study?
Does interferon-alpha induce arrhythmogenic and inotropic effects in rat hearts, and are these effects influenced by cardiac hypertrophy and isoproterenol?
Does interferon-alpha induce arrhythmogenic and inotropic effects in rat hearts, and are these effects influenced by cardiac hypertrophy and isoproterenol?
Absolute Event Rate: 4% vs 0.75%
p-value: p=<0.05
The arrhythmogenic effects of interferon-alpha are potentiated by pathophysiological conditions such as cardiac hypertrophy and elevated sympathetic activity.
Interferon-alpha may heighten arrhythmia risk in hypertrophied hearts under sympathetic stress; leaves open human translation.
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.
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Odashiro et al. (2002) studied Cardiac hypertrophy (n=52). Interferon-alpha (with or without isoproterenol) vs. Control (sham-operated) rats and baseline was evaluated on Arrhythmic score (0-8 scale) following sequential application of isoproterenol and interferon-alpha in vivo (p=<0.05). Interferon-alpha induced ventricular tachyarrhythmias and atrioventricular blockade in rat hearts, with arrhythmogenesis significantly potentiated by cardiac hypertrophy and isoproterenol pretreatment.
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