N G Yousif1,2, N R Hadi3, F Al-Amran4, Q A Zigam3. 1. Department of Medicine, Muthanna Medical College, Samawah, Iraq. yousif_ghaly@yahoo.com. 2. Anschutz | Medical School, University of Colorado, Denver, USA. yousif_ghaly@yahoo.com. 3. Department of Pharmacology and Therapeutics, Kufa Medical College, University Kufa, Kufa, Iraq. 4. Department of Thoracic Surgery, Kufa Medical College, University Kufa, Kufa, Iraq.
Abstract
BACKGROUND: Sepsis is a systemic inflammatory response usually correlated with multi-organ failure. Myocardial dysfunction is one of the adverse outcomes in septic patients and results in high mortality rates. The aim of this study was to investigate the impact of irbesartan in attenuation of cardiac depression during polymicrobial sepsis via decreased activation of the phospho-p38MAPK/nuclear factor (NF)-κB signaling pathway. MATERIALS AND METHODS: A model of polymicrobial sepsis induced via cecal ligation and puncture (CLP) with 8- to 12-week-old albino mice was used. Mice were treated with i.p. irbesartan (3 mg/kg) 1 h before CLP. Using a micro-tipped transducer catheter, the following hemodynamic parameters were evaluated after CLP: heart rate, ejection fraction, left ventricular (LV) end-diastolic pressure, LV systolic pressure, and cardiac output. Plasma levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, monocyte chemoattractant protein-1 (MCP-1), and cardiac troponin I (cTn-I), were measured via ELISA analysis. The degree of p38MAPK and NF-κB phosphorylation was assessed via Western blotting. RESULTS: Mice treated with irbesartan displayed improvement in LV function (ejection fraction: 42.4 ± 1.1% vs. 27.8 ± 3% in CLP mice). The attenuation of cardiac depression in irbesartan-treated mice was associated with lower levels of MCP-1 in plasma and a reduction in the levels of TNF-alpha, IL-1beta, and IL-6. Furthermore, irbesartan-treated mice displayed lower expression levels of p38-MAPK and NF-κB phosphorylation. CONCLUSION: Irbesartan can attenuate cardiac dysfunction during polymicrobial sepsis possibly via a reduction of proinflammatory cytokines through decreased activation of the p38MAPK/NF-κB pathways.
BACKGROUND:Sepsis is a systemic inflammatory response usually correlated with multi-organ failure. Myocardial dysfunction is one of the adverse outcomes in septic patients and results in high mortality rates. The aim of this study was to investigate the impact of irbesartan in attenuation of cardiac depression during polymicrobial sepsis via decreased activation of the phospho-p38MAPK/nuclear factor (NF)-κB signaling pathway. MATERIALS AND METHODS: A model of polymicrobial sepsis induced via cecal ligation and puncture (CLP) with 8- to 12-week-old albino mice was used. Mice were treated with i.p. irbesartan (3 mg/kg) 1 h before CLP. Using a micro-tipped transducer catheter, the following hemodynamic parameters were evaluated after CLP: heart rate, ejection fraction, left ventricular (LV) end-diastolic pressure, LV systolic pressure, and cardiac output. Plasma levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-6, monocyte chemoattractant protein-1 (MCP-1), and cardiac troponin I (cTn-I), were measured via ELISA analysis. The degree of p38MAPK and NF-κB phosphorylation was assessed via Western blotting. RESULTS:Mice treated with irbesartan displayed improvement in LV function (ejection fraction: 42.4 ± 1.1% vs. 27.8 ± 3% in CLPmice). The attenuation of cardiac depression in irbesartan-treated mice was associated with lower levels of MCP-1 in plasma and a reduction in the levels of TNF-alpha, IL-1beta, and IL-6. Furthermore, irbesartan-treated mice displayed lower expression levels of p38-MAPK and NF-κB phosphorylation. CONCLUSION:Irbesartan can attenuate cardiac dysfunction during polymicrobial sepsis possibly via a reduction of proinflammatory cytokines through decreased activation of the p38MAPK/NF-κB pathways.
Authors: Konstantinos Drosatos; Anastasios Lymperopoulos; Peter Johannes Kennel; Nina Pollak; P Christian Schulze; Ira J Goldberg Journal: Curr Heart Fail Rep Date: 2015-04
Authors: Ciro Coletta; Katalin Módis; Gábor Oláh; Attila Brunyánszki; Daniela S Herzig; Edward R Sherwood; Zoltán Ungvári; Csaba Szabo Journal: Crit Care Date: 2014-09-16 Impact factor: 9.097