Heart Rate Control during Experimental Sepsis in Mice: Comparison of Ivabradine and β-Blockers. (February 2020)

• Record Type: Journal Article
• Authors: Bedet, Alexandre; Voiriot, Guillaume; Ternacle, Julien; Marcos, Elisabeth; Adnot, Serge; Derumeaux, Geneviève; Mekontso Dessap, Armand
• Is Part Of: Anesthesiology. Volume 132:Number 2(2020)
• Publication Date: 2020-02
• Subjects: Anesthesiology -- Periodicals; Anesthetics -- Periodicals; Anesthesia -- Periodicals; 617.9605
• DOI: 10.1097/ALN.0000000000003045
• Languages: English
• ISSNs: 0003-3022

Abstract

Abstract : 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 I f 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. Abstract : 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.