Newly Published
Critical Care Medicine  |   November 2019
Heart Rate Control during Experimental Sepsis in Mice: Comparison of Ivabradine and β-Blockers
Author Notes
  • From Greater Paris Public Hospitals (Assistance Publique–Hôpitaux de Paris), Henri Mondor University Hospital, Ageing Thorax-Vessels-Blood Department, Departments of Intensive Care (A.B., A.M.D.), Cardiology (J.T.), and Functional Explorations (S.A., G.D.), Créteil, France; University Paris East Creteil, Mondor Institute of Biomedical Research, CARMAS Research Group (A.B., G.V., A.M.D.) and Team 8 (J.T., E.M., S.A., G.D.), Créteil, France; and Greater Paris Public Hospitals (Assistance Publique–Hôpitaux de Paris), Tenon Hospital, Intensive Care Unit, Paris, France (G.V.).
  • Part of the work in this article has been presented at the European Society of Cardiology Congress in Barcelona, Spain, August 27, 2017.
    Part of the work in this article has been presented at the European Society of Cardiology Congress in Barcelona, Spain, August 27, 2017.×
  • Submitted for publication January 21, 2019. Accepted for publication October 10, 2019.
    Submitted for publication January 21, 2019. Accepted for publication October 10, 2019.×
  • Correspondence: Address correspondence to Dr. Bedet: Henri Mondor University Hospital, Ageing Thorax-Vessels-Blood Department, Department of Intensive Care, Créteil, F-94010 France. alexandre.bedet@gmail.com. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Critical Care Medicine / Cardiovascular Anesthesia / Critical Care / Gastrointestinal and Hepatic Systems
Critical Care Medicine   |   November 2019
Heart Rate Control during Experimental Sepsis in Mice: Comparison of Ivabradine and β-Blockers
Anesthesiology Newly Published on November 19, 2019. doi:https://doi.org/10.1097/ALN.0000000000003045
Anesthesiology Newly Published on November 19, 2019. doi:https://doi.org/10.1097/ALN.0000000000003045
Abstract

Editor’s Perspective:

What We Already Know about This Topic:

  • Tachycardia is known to occur with sepsis and can result in decreased ventricular filling and increased myocardial oxygen demand.

  • β-Blockers or ivabradine (a selective inhibitor of If channels in the sinoatrial node) are drugs that can be used to treat tachycardia in the setting of sepsis. However, because of its selective inhibition in the sinoatrial node, ivabradine should not suppress myocardial contractility in the same manner as β-blockers.

What This Article Tells Us That Is New:

  • This study assesses the effects of ivabradine, atenolol, and placebo in the setting of murine peritonitis. Mice that received atenolol versus ivabradine both experienced a similar and significant decline in heart rate. The mice in the atenolol group also experienced a significant decrease in cardiac output, systolic blood pressure, and left ventricular systolic function that was not experienced by the mice who received ivabradine.

  • Mice who received atenolol versus ivabradine versus placebo did not have significantly different survival 60 h after induction of sepsis. Future studies are needed to determine the value of ivabradine versus atenolol for heart rate control in human sepsis.

Background: Tachycardia is a hallmark of sepsis. An elevated heart rate could impair ventricular filling and increase myocardial oxygen demand. β-Blockers and ivabradine (a selective inhibitor of If channels in the sinoatrial node) are both able to control sinus tachycardia, with the latter drug being devoid of negative inotropic effect. This work aimed at assessing the hemodynamic effects of ivabradine as compared with a β-blocker (atenolol) during murine peritonitis.

Methods: Ivabradine (3 μg/g), atenolol (3 μg/g), or placebo was administered intraperitoneally 2 h after induction of peritonitis (cecal ligation and puncture) in male C57BL6 mice. The authors used invasive (left ventricular catheterization) and noninvasive (transthoracic echocardiography) monitoring to assess hemodynamics 20 h after surgery, including heart rate, blood pressure, left ventricular systolic, and diastolic function (n = 10 mice/group). The authors also assessed overall mortality 30 and 60 h after surgery in a distinct subset of animals (n = 20 mice/group). Descriptive data are presented as median (25th to 75th percentile).

Results: As compared with placebo (601 beats/min [547 to 612]), ivabradine (447 beats/min [430 to 496]) and atenolol (482 beats/min [412 to 505]) blunted sepsis-induced tachycardia assessed by transthoracic echocardiography in awake animals (P < 0.001 and P = 0.004, respectively). Unlike ivabradine, atenolol reduced cardiac output, systolic blood pressure, and left ventricular systolic function (as assessed by ejection fraction, maximal left ventricular pressure rise, and anterior wall strain rate) as compared with septic mice receiving placebo. There was no difference in survival 60 h after sepsis induction with ivabradine (6 of 20, 30%) or atenolol (7 of 20, 35%), as compared with placebo (5 of 20, 25%; P = 0.224).

Conclusions: Heart rate control could be similarly achieved by ivabradine or atenolol, with preservation of blood pressure, cardiac output, and left ventricular systolic function with the former drug.