Effects of low doses of esmolol on cardiac and vascular function in experimental septic shock. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Wei, Chaojie; Louis, Huguette; Schmitt, Margaux; Albuisson, Eliane; Orlowski, Sophie; Levy, Bruno; Kimmoun, Antoine
• Is Part Of: Critical care. Volume 20:Issue 1(2016)
• Page Start: 1
• Page End: 10
• Publication Date: 2016-12
• Subjects: Sepsis -- Esmolol -- Heart function -- Vasoreactivity -- Inflammation; Critical care medicine -- Periodicals; 616.02805
• DOI: 10.1186/s13054-016-1580-2
• Languages: English
• ISSNs: 1364-8535

Abstract

Abstract Background Administration of a selective β1-blocker, such as esmolol, in human septic shock has demonstrated cardiovascular protective effects related to heart rate reduction. Certain experimental data also indicate that esmolol exerts systemic anti-inflammatory and beneficial effects on vascular tone. Thus, the present study aimed to determine whether a non-chronotropic dose of esmolol maintains its protective cardiovascular and anti-inflammatory effects in experimental septic shock. Methods Four hours after cecal ligation and puncture (CLP), Wistar male rats were randomly allocated to the following groups (n = 8): CLP, CLP + E-1 (esmolol: 1 mg.kg−1 .h−1 ), CLP + E-5 (esmolol: 5 mg.kg−1 .h−1 ), CLP + E-18 (esmolol: 18 mg.kg−1 .h−1 ). An additional eight rats underwent sham operation. All rats received a continuous infusion of saline, analgesic and antibiotics 4 hours after the surgery. Assessment at 18 hours included in vivo cardiac function assessed by echocardiography and ex vivo vasoreactivity assessed by myography. Circulating cytokine levels (IL-6 and IL-10) were measured by ELISA. Cardiac and vascular protein expressions of p-NF-κB, IκBα, iNOS, p-AKT/AKT and p-eNOS/eNOS were assessed by western blotting. Results CLP induced tachycardia, hypotension, cardiac output reduction, hyperlactatemia and vascular hypo-responsiveness to vasopressors. Compared to CLP animals, heart rate was unchanged in CLP + E-1 and CLP + E-5 but was reduced in CLP + E-18. Stroke volume, cardiac output, mean arterial pressure and lactatemia were improved in CLP + E-1 and CLP + E-5, while vascular responsiveness to phenylephrine was only improved in CLP + E-5 and CLP + E-18. Plasma IL-6 levels were decreased in all esmolol groups. p-NF-κB was decreased in both cardiac and vascular tissues in CLP + E-5 and CLP + E-18. Conclusion In experimental septic shock, low doses of esmolol still improved cardiac function and vasoreactivity. These benefits appear to be associated with a modulation of inflammatory pathways.