Critical Care Medicine  |   January 2017
Ivabradine Attenuates the Microcirculatory Derangements Evoked by Experimental Sepsis
Author Notes
  • From the Laboratory for Clinical and Experimental Research in Vascular Biology - BioVasc, Department of Physiological Sciences, Biomedical Center, Rio de Janeiro State University, Rio de Janeiro, Brazil (M.L.M., D.S.B., L.S.P., M.-C.S.S., E.B.); and Internal Medicine Department, Andaraí Federal Hospital, Rio de Janeiro, Brazil (M.M.B.).
  • Submitted for publication April 2, 2016. Accepted for publication September 23, 2016.
    Submitted for publication April 2, 2016. Accepted for publication September 23, 2016.×
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    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org).×
  • Address correspondence to Dr. Miranda: Laboratory for Clinical and Experimental Research in Vascular Biology - BioVasc, Pavilhão Reitor Haroldo Lisboa da Cunha, Rio de Janeiro State University, Rua São Francisco Xavier 524, 20550-013 Rio de Janeiro, Brazil. marcoslmiranda@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 / Basic Science / Cardiovascular Anesthesia / Critical Care / Gastrointestinal and Hepatic Systems / Infectious Disease / Renal and Urinary Systems / Electrolyte Balance / Respiratory System
Critical Care Medicine   |   January 2017
Ivabradine Attenuates the Microcirculatory Derangements Evoked by Experimental Sepsis
Anesthesiology 1 2017, Vol.126, 140-149. doi:10.1097/ALN.0000000000001431
Anesthesiology 1 2017, Vol.126, 140-149. doi:10.1097/ALN.0000000000001431
Abstract

Background: Experimental data suggest that ivabradine, an inhibitor of the pacemaker current in sinoatrial node, exerts beneficial effects on endothelial cell function, but it is unclear if this drug could prevent microcirculatory dysfunction in septic subjects, improving tissue perfusion and reducing organ failure. Therefore, this study was designed to characterize the microcirculatory effects of ivabradine on a murine model of abdominal sepsis using intravital videomicroscopy.

Methods: Twenty-eight golden Syrian hamsters were allocated in four groups: sham-operated animals, nontreated septic animals, septic animals treated with saline, and septic animals treated with ivabradine (2.0 mg/kg intravenous bolus + 0.5 mg · kg−1 · h−1). The primary endpoint was the effect of ivabradine on the microcirculation of skinfold chamber preparations, assessed by changes in microvascular reactivity and rheologic variables, and the secondary endpoint was its effects on organ function, evaluated by differences in arterial blood pressure, motor activity score, arterial blood gases, and hematologic and biochemical parameters among groups.

Results: Compared with septic animals treated with saline, those treated with ivabradine had greater functional capillary density (90 ± 4% of baseline values vs. 71 ± 16%; P < 0.001), erythrocyte velocity in capillaries (87 ± 11% of baseline values vs. 62 ± 14%; P < 0.001), and arteriolar diameter (99 ± 4% of baseline values vs. 91 ± 7%; P = 0.041) at the end of the experiment. Besides that, ivabradine-treated animals had less renal, hepatic, and neurologic dysfunction.

Conclusions: Ivabradine was effective in reducing microvascular derangements evoked by experimental sepsis, which was accompanied by less organ dysfunction. These results suggest that ivabradine yields beneficial effects on the microcirculation of septic animals.