Abstract
Objective Previous studies have suggested that lowering heart rate by selective β1-blockers improves sepsis-induced cardiac and vascular dysfunction primarily by decreasing pro-inflammatory pathways. However, the impact of isolated heart rate reduction on hemodynamics and inflammatory pathways remains unknown. The present study was designed to assess the effects of heart rate reduction by Ivabradine, an If channel inhibitor, on cardiovascular function and inflammatory pathways in peritonitis-induced septic shock in rats. Interventions four hours after cecal ligation and puncture (CLP), Wistar rats were randomly allocated to the following groups: CLP (n=8) and Ivabradine (n=8, administered per os at H4). Another eight Wistar male rats underwent sham operation. All rats received a continuous infusion of saline (10 ml.kg-1.h-1), analgesic (nalbuphin: 0.2 mg.kg-1.h-1) and antibiotics (Imipenem and Cilastatin Sodium: 10 mg/kg) four hours after the surgery. Assessment at 18 hours included hemodynamics, in vivo cardiac function by echocardiography and ex vivo vasoreactivity by myography. Cardiac and vascular expressions of NF-κB and eNOS/Akt/iNOS pathways was assessed by western blot. Results Compared to sham animals, CLP induced tachycardia, hypotension, decreased cardiac output, hyperlactatemia and vascular hyporesponsiveness to vasopressors. Compared to the CLP group, adjunction of Ivabradine decreased the heart rate without any impact on blood pressure, lactatemia or vascular responsiveness to vasopressors. Cardiac output was decreased albeit without reaching statistical significance. Ivabradine had no impact on cardiac and vascular protein expression levels of the phosphorylated forms of NF-κB, Akt, eNOS, iNOS. Conclusion Isolated reduction of heart rate by Ivabradine in an experimental model of septic shock does not result in any effect on cardiovascular function and inflammatory pathways. The author hereby declares no conflict of interest
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