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. 2018 Apr 3;8:5478. doi: 10.1038/s41598-018-23304-7

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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BRL44408 (BRL) therapy improves survival and reverses cardiac dysfunction and hypotension in septic rats. The rats were randomized into sham, cecal ligation and puncture (CLP), CLP+BRL and sham+BRL (BRL) groups. The rats were subjected to CLP or sham surgery and were treated intraperitoneally with either BRL (i.p.) or normal saline 4 h later. (A): A Kaplan-Meier plot indicating that treatment with BRL (1.5 or 3.0 mg/kg) significantly improves the survival of septic rats (n = 10 for each group). (B): The mean arterial pressure (MAP) was measured 20 h after CLP or sham surgery using the tail-cuff method, and BRL (1.5 mg/kg) elevated the MAP in septic rats. (C,D) and (E): Echocardiography evaluation indicated that BRL (1.5 mg/kg) treatment increased left ventricular ejection fraction (EF), but not left ventricular end-diastolic volume (LVEDV) in septic rats. (F) and (G): The hearts were obtained 20 h after CLP or sham surgery and left ventricular function was assessed in a Langendorff apparatus. The maximum rates of the rise (+dP/dt) and fall (−dP/dt) of the left ventricular pressure 30 min after perfusion are shown. BRL (1.5 mg/kg) increased +dP/dt and −dP/dt in CLP rats. (H): Left ventricle samples were obtained for the Western blot analysis 20 h after CLP or sham surgery, and BRL (1.5 mg/kg) inhibited left ventricular cardiac troponin I (cTnI,) phosphorylation (Ser23/24) in septic rats. n = 7 for the sham and the BRL groups, n = 10 for the CLP and the CLP+BRL groups. Statistical significance is shown as *P < 0.05.