Ivabradine preserves dynamic sympathetic control of heart rate despite inducing significant bradycardia in rats

• Published in: The journal of physiological sciences Vol. 69; no. 2; pp. 211 - 222
• Main Authors: Kawada, Toru, Shimizu, Shuji, Uemura, Kazunori, Hayama, Yohsuke, Yamamoto, Hiromi, Shishido, Toshiaki, Nishikawa, Takuya, Sugimachi, Masaru
• Format: Journal Article
• Language: English
• Published: Japan Springer 01.03.2019; BioMed Central; Springer Japan
• Subjects: Animals; Blood Pressure - drug effects; Bradycardia; Bradycardia - drug therapy; Bradycardia - metabolism; Cardiac arrhythmia; Heart beat; Heart rate; Heart Rate - drug effects; Hyperpolarization; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - metabolism; Intravenous administration; Ion channels (cyclic nucleotide-gated); Ivabradine; Ivabradine - pharmacology; Male; Metoprolol; Metoprolol - pharmacology; Original Paper; Rats; Rats, Inbred WKY; Rodents; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - metabolism; Japan; Transfer function; Sympathetic stimulation; Metoprolol
• ISSN: 1880-6546; 1880-6562
• DOI: 10.1007/s12576-018-0636-2

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.