Thromboelastography evaluation for hemostatic dysfunction in severe sepsis and septic shock: An experience from tertiary care center in North India

Abstract

The roles of the ACE inhibitor captopril on inflammatory response in septic human neutrophil and mortality in endotoxemic mice SanghyeonKwak, Taehee Pyeon, Jia Song, Euna Jang, Hyeonjeong Lee, Jeongmin Kim Chonnam National University Medical School, Republic of Korea Chonnam National University Hospital, Republic of Korea Chonnam National University Hwasun Hospital, Republic of Korea Background/Purpose: Angiotensin-converting enzyme (ACE) mediates inflammatory response in healthy lungs via angiotensin II and plasminogen activator inhibitor 1. Neutrophils play an important role in the development of acute lung injury associated with severe sepsis. However, the ability of ACE directly participating in LPSinduced neutrophil activation has not been fully examined. This study was performed to evaluate the effects of the ACE inhibitor captopril on lipopolysaccharide (LPS)–induced neutrophil activation and mortality in LPS-induced endotoxemic mice. Methods: To assess possible interactions between captopril and LPS on neutrophil activation, neutrophils from human blood were incubated with various concentrations of captopril (0, 1, 10, 50, and 100 nM) and LPS (100 ng/mL). The protein levels for interleukins (ILs) 6 and 8 and tumor necrosis factor (TNF) α were measured using enzyme-linked immunosorbent assay 4 hours after incubation period. To elucidate the intracellular signaling pathway, we measured the levels of phosphorylation of p38 mitogen-activated protein kinases (p38), extracellular signal-regulated kinase (ERK) 1/2 and c-Jun amino-terminal kinases (JNK) with Western blot analysis and nuclear levels of nuclear factor (NF) κB with electrophoretic mobility shift assays 0.5 hours after incubation period. We also examined the effect of captopril (30 mg/kg, IP) on mortality of mice treated with LPS (20 mg/kg, IP) to determine whether these effects of captopril also have in vivo significance. Results: Captopril attenuated LPS-induced neutrophils activation including expression of p38, JNK, NF-κB, IL-6, IL-8, and TNF-α. Captopril also attenuated mortality in LPS-induced endotoxemic mice. Conclusions: Captopril can attenuate mortality in LPS-induced endotoxemic mice via the attenuation of neutrophil activation caused by LPS.