Was achieved using hydroxyethyl starch (up to 20 ml/kg) and norepinephrine infusion (up to 10

Was achieved using hydroxyethyl starch (up to 20 ml/kg) and norepinephrine infusion (up to 10 g/kg/ minute). Results: Hemodynamic parameters were continuously recorded. Gas exchange, acid-base status, organ function, and cytokines were measured at regular intervals until 24 hours after the onset of peritonitis when animals were sacrificed under anesthesia. Peritonitis induced profound hypotension, myocardial dysfunction, lactic acidosis, coagulation abnormalities, and multiple organ failure. These disorders were largely QVD-OPH web attenuated by LR12. In particular, cardiovascular failure was prevented as attested by better mean arterial pressure, cardiac index, cardiac power index, and SvO2, despite lower norepinephrine requirements (Figure 1). Finally, 24-hour mortality rates were respectively 60 and 0 for control and LR12 groups. Conclusion: LR12, a TLT-1 derived peptide, exhibits salutary properties during septic shock in adult mini-pigs. Reference 1. Derive M, Bouazza Y, Sennoun N, Marchionni S, Quigley L, Washington V, Massin F, Max JP, Ford J, Alauzet C, Levy B, McVicar DW, Gibot S: Soluble TREM-like transcript-1 regulates leukocyte activation and controls microbial sepsis. J Immunol 2012, 188:5585-5592.Critical Care 2012, Volume 16 Suppl 3 http://ccforum.com/supplements/16/SPage 26 ofFigure 1(abstract P48) LR12 protects from sepsis-induced hypotension. Evolution of mean arterial pressure (a) and norepinephrine requirements (b) during the 24-hour study period. MAP was constantly higher and norepinephrine dose lower in LR12-treated animals than controls.P49 Role of TREM-1 in endothelial dysfunction during experimental sepsis A Boufenzer1*, N Sennoun1, Y Bouazza1, M Derive1, PE Bollaert2, S Gibot2 1 Groupe CHOC – Inserm U961, Nancy University, Nancy, France; 2CHU Nancy, France Critical Care 2012, 16(Suppl 3):P49 Background: Triggering receptor expressed on myeloid cells-1 (TREM-1) is a receptor of the immunoglobulin superfamily expressed on the surface of neutrophils and monocytes/macrophages. It plays an important role during sepsis by amplifying the inflammatory response. Modulation of TREM-1 through the administration of a short synthetic peptide (LR12) increases survival during experimental sepsis. This study aimed to explore the mechanisms by which LR12 prevented sepsis-induced cardiovascular dysfunction. Methods: We studied the effect of TREM-1 modulation by a synthetic peptide LR12 (3 mg/kg) on MAP and blood lactate during experimental sepsis (CLP). Aortic and mesenteric arterial vessels of these animals were collected to study the vasoreactivity to phenylephrine (Phe) and acetylcholine (Ach) ex vivo (Myograph). Alternatively, vasoreactivity was studied in the vessels of healthy animals (with and without endothelial lawyer) stimulated with LPS or with a specific agonist of TREM-1 (aTREM1, 10 g/ml), with PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26100631 or without LR12 (20 mg/ml). The effect of LR12 on arterial vessels was also studied through western blotting (eNOS, iNOS, Akt, COX-1, COX-2) and qRT-PCR. Mouse lung microvascular endothelial cells (LUMECs; CD146+) were analyzed by flow cytometry, qRT-PCR, and ELISA to decipher the effect of LR12 on LPS-induced endothelial activation. Results: CLP induced MAP decrease and lactate elevation were prevented by the administration of LR12. Arterial vessels from septic animals treated with LR12 showed better response to Phe and Ach compared with controls. The reactivity of aortic and mesenteric vessels (contraction and relaxation) stimulated.