1. If Channel Inhibition With Ivabradine Does Not Improve Cardiac and Vascular Function in Experimental Septic Shock
- Author
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Huguette Louis, Narimane Al Kattani, Antoine Kimmoun, Eliane Albuisson, Bruno Levy, Chaojie Wei, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), ESPRI-Biobase [CHRU Nancy] (Unité fonctionnelle de la plateforme d’aide à la recherche clinique), Institut Élie Cartan de Lorraine (IECL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Réanimation Médicale [CHRU Nancy], and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
- Subjects
Male ,MESH: Interleukin-10 ,Hemodynamics ,030204 cardiovascular system & hematology ,Critical Care and Intensive Care Medicine ,0302 clinical medicine ,Heart Rate ,Ivabradine ,MESH: Animals ,MESH: Heart Rate ,Cecum ,Shock, Septic ,3. Good health ,Interleukin-10 ,Echocardiography ,Shock (circulatory) ,Anesthesia ,Emergency Medicine ,Cardiology ,Tumor necrosis factor alpha ,MESH: Benzazepines ,medicine.symptom ,MESH: Cardiovascular Agents ,medicine.drug ,medicine.medical_specialty ,MESH: Hemodynamics ,MESH: Rats ,MESH: Shock, Septic ,Proinflammatory cytokine ,03 medical and health sciences ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Internal medicine ,Heart rate ,medicine ,Animals ,Rats, Wistar ,Ligation ,business.industry ,Septic shock ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,030208 emergency & critical care medicine ,Cardiovascular Agents ,MESH: Cecum ,MESH: Rats, Wistar ,Benzazepines ,MESH: Ligation ,medicine.disease ,MESH: Interleukin-6 ,MESH: Male ,Rats ,MESH: Tumor Necrosis Factor-alpha ,Cardiovascular agent ,MESH: Echocardiography ,business - Abstract
International audience; OBJECTIVE:Previous studies have suggested that lowering heart rate (HR) by selective β1-blockers improves sepsis-induced cardiac and vascular dysfunction primarily by decreasing proinflammatory pathways. However, the impact of isolated heart rate reduction (HRR) on hemodynamics and inflammatory pathways remains unknown. The present study was designed to assess the effects of HRR by ivabradine, an If channel inhibitor, on cardiovascular function and inflammatory pathways in peritonitis-induced septic shock in rats.DESIGN:Randomized animal study.SETTING:University research laboratory.INTERVENTIONS:Four hours after cecal ligation and puncture (CLP), Wistar rats were randomly allocated to the following groups: CLP (n = 8) and CLP + ivabradine (n = 8, administered per os 4 h after the surgery). Another eight Wistar male rats underwent sham operation. All rats received a continuous infusion of saline (10 mL kg h), analgesic (nalbuphine: 0.2 mg kg h), and antibiotics (imipenem and cilastatin sodium: 10 mg kg) 4 h after the surgery. Assessment at 18 h included hemodynamics, in vivo cardiac function by echocardiography, and ex vivo vasoreactivity by myography. Circulating cytokine levels (TNF-α, IL-6, and IL-10) were measured by ELISA, whereas cardiac and vascular protein expressions of NF-κB/IκBα/iNOS and Akt/eNOS were assessed by Western blotting.RESULTS:Compared with sham animals, CLP induced tachycardia, hypotension, decreased cardiac output, hyperlactatemia, and vascular hyporesponsiveness to vasopressors. Compared with the CLP group, adjunction of ivabradine decreased the HR without any impact on blood pressure, lactatemia, or vascular responsiveness to vasopressors. Adjunction of ivabradine to CLP rats had no impact on TNF-α, IL-6, and IL-10 cytokines, or on the protein expression levels of phosphorylated forms of NF-κB, Akt, eNOS, and degradation of IκBα in cardiac and vascular tissues.CONCLUSION:Isolated HRR by ivabradine in an experimental model of septic shock does not appear to be associated with any effect on the tested parameters of cardiac function or on vascular responsiveness to vasopressors. Moreover, in this setting, ivabradine does not alter the circulating levels of selected pro/anti-inflammatory cytokines or cardiac and vascular NF-κB/IκBα protein expression levels.
- Published
- 2016