Ivabradine does not acutely affect open-loop baroreflex static characteristics and spares sympathetic heart rate control in rats

Int J Cardiol. 2018 Apr 15:257:255-261. doi: 10.1016/j.ijcard.2017.11.115.

Abstract

Aims: To assess the acute effects of intravenous ivabradine, a selective bradycardic agent, on carotid sinus baroreflex-mediated sympathetic arterial pressure (AP) and heart rate (HR) responses.

Methods and results: In anesthetized and vagotomized Wistar-Kyoto rats (n=6), carotid sinus baroreceptor regions were isolated. Changes in splanchnic sympathetic nerve activity (SNA), AP, and HR in response to a step-wise pressure input were examined before and after intravenous ivabradine (2mg/kg). Ivabradine did not affect the response range of SNA (91.8±6.5 vs. 93.5±9.8%) or AP (89.6±10.6 vs. 91.0±9.7mmHg). Ivabradine significantly reduced the minimum HR from 369.4±8.4 to 223.3±13.2 (P<0.001) but did not attenuate the HR response range (69.1±7.0 vs. 82.5±9.6beats/min).

Conclusions: Ivabradine does not acutely affect baroreflex-mediated sympathetic AP regulation and also spares the magnitude of the sympathetic HR response, despite significant bradycardia. The preserved sympathetic HR response, which could not be afforded by beta-blockers, may contribute to some beneficial clinical effects of ivabradine.

Keywords: Carotid sinus baroreflex; Heart rate; Ivabradine; Open-loop system analysis; Sympathetic nerve activity.

MeSH terms

  • Animals
  • Baroreflex / drug effects*
  • Baroreflex / physiology
  • Benzazepines / pharmacology*
  • Blood Pressure / drug effects*
  • Blood Pressure / physiology
  • Cardiovascular Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Heart Rate / drug effects*
  • Heart Rate / physiology
  • Ivabradine
  • Pressoreceptors / drug effects*
  • Pressoreceptors / physiology
  • Rats
  • Rats, Inbred WKY
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / physiology

Substances

  • Benzazepines
  • Cardiovascular Agents
  • Ivabradine