Does intravenous ivabradine preserve dynamic sympathetic control of heart rate compared to metoprolol in anesthetized rats?
Ivabradine preserves dynamic sympathetic control of heart rate while inducing bradycardia, unlike metoprolol, which may explain some of its unique clinical benefits.
Ivabradine is a selective bradycardic agent that inhibits hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. HCN channels play a key role in mediating the positive chronotropic response to sympathetic nerve stimulation (SNS). We examined whether ivabradine would interfere with dynamic sympathetic control of heart rate (HR). The effect of intravenous ivabradine (2 mg/kg, n = 7) or metoprolol (10 mg/kg, n = 6) on the transfer function from SNS to HR was examined in anesthetized rats. Ivabradine preserved the asymptotic dynamic gain of the HR transfer function and nearly doubled the asymptotic dynamic gain of the transfer function from SNS to the R-R interval. In contrast, metoprolol abolished dynamic sympathetic control of HR. Preserved dynamic sympathetic control of HR, with coexisting bradycardia, may contribute to some of the beneficial effects of ivabradine previously reported in clinical application.
Kawada et al. (2018) studied this question.