V. Schmidt, H. Werdan, K. Müller-werdan, and U. , Autonomic dysfunction in the ICU patient, Current Opinion in Critical Care, vol.7, issue.5, pp.314-322, 2001.
DOI : 10.1097/00075198-200110000-00002

M. Levy, 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference, SIS International Sepsis Definitions Conference, pp.1250-1256, 2001.
DOI : 10.1097/01.CCM.0000050454.01978.3B

T. Pottecher, Conférence de consensus, pp.418-419, 2006.

P. Moine, K. Asehnoune, A. Edouard, and D. Payen, Immunomodulation and sepsis -Impact of the microorganisms, pp.182-191, 2003.

L. López-bojórquez, A. Dehesa, and G. Reyes-terán, Molecular mechanisms involved in the pathogenesis of septic shock. Archives of Medical Research, pp.465-479, 2004.

R. Danner, R. Elin, J. Hosseini, R. Wesley, J. Reilly et al., Endotoxemia in Human Septic Shock, Chest, vol.99, issue.1, pp.169-175, 1991.
DOI : 10.1378/chest.99.1.169

A. Suffredini, R. Fromm, M. Parker, M. Brenner, J. Kovacs et al., The Cardiovascular Response of Normal Humans to the Administration of Endotoxin, New England Journal of Medicine, vol.321, issue.5, pp.280-287, 1989.
DOI : 10.1056/NEJM198908033210503

R. Andriantsitohaina, G. Lagaud, A. Andre, B. Muller, and J. Stoclet, Effects of cGMP on calcium handling in ATP-stimulated rat resistance arteries, American Journal of Physiology-Heart and Circulatory Physiology, vol.268, issue.3, pp.1223-1231, 1995.
DOI : 10.1152/ajpheart.1995.268.3.H1223

K. Comstock, K. Krown, M. Page, D. Martin, P. Ho et al., LPS-induced TNF-alpha release from and apoptosis in rat cardiomyocytes: obligatory role for CD14 in mediating the LPS response, J Mol Cell Cardiol, issue.12, pp.302761-2775, 1998.

D. Cowan, S. Noria, C. Stamm, L. Garcia, D. Poutias et al., Lipopolysaccharide Internalization Activates Endotoxin-Dependent Signal Transduction in Cardiomyocytes, Circulation Research, vol.88, issue.5, pp.491-498180, 1995.
DOI : 10.1161/01.RES.88.5.491

S. Liu and A. Malik, NF-??B activation as a pathological mechanism of septic shock and inflammation, American Journal of Physiology-Lung Cellular and Molecular Physiology, vol.290, issue.4, pp.622-645125, 2002.
DOI : 10.1152/ajpgi.00431.2002

O. Huet, G. Choukroun, and M. J. , Toll like receptor, inflammatory response and sepsis. Réanimation, pp.167-175, 2004.

M. Adib-conquy and J. Cavaillon, Stress molecules in sepsis and systemic inflammatory response syndrome, FEBS Letters, vol.7, issue.19, pp.5813723-3733, 2007.
DOI : 10.1016/S1473-3099(07)70052-X

P. Ghezzi, C. Dinarello, M. Bianchi, M. Rosandich, J. Repine et al., Hypoxia increases production of interleukin-1 and tumor necrosis factor by human mononuclear cells AR: Sensitization to lipopolysaccharide in mice with asymptomatic viral infection: role of T cell-dependent production of interferon-gamma, Cytokine J Infect Dis, vol.3, issue.1761, pp.189-194151, 1991.

H. Gerlach, M. Gerlach, M. Clauss, W. Smith, D. Dewitt et al., Relevance of tumour necrosis factor-alpha and interleukin-1-alpha in the pathogenesis of hypoxia-related organ failure, Eur J Anaesthesiol CYCLOOXYGENASES: Structural, Cellular, and Molecular Biology. Annual Review of Biochemistry, vol.10, issue.691, pp.273-285145, 1993.

S. Moncada, R. M. Palmer, and E. Higgs, Biosynthesis of nitric oxide from l-arginine, Biochemical Pharmacology, vol.38, issue.11, pp.1709-1715, 1989.
DOI : 10.1016/0006-2952(89)90403-6

H. Macarthur, T. Westfall, D. Riley, T. Misko, and D. Salvemini, Inactivation of catecholamines by superoxide gives new insights on the pathogenesis of septic shock, Proceedings of the National Academy of Sciences, vol.62, issue.5, pp.979753-9758, 2000.
DOI : 10.1172/JCI118469

C. Daveu, C. Servy, M. Dendane, P. Marin, and C. Ducrocq, Oxidation and Nitration of Catecholamines by Nitrogen Oxides Derived from Nitric Oxide, Nitric Oxide, vol.1, issue.3, pp.234-243, 1997.
DOI : 10.1006/niox.1997.0123

F. Shintani, T. Kinoshita, S. Kanba, T. Ishikawa, E. Suzuki et al., Bioactive 6-Nitronorepinephrine Identified in Mammalian Brain, Journal of Biological Chemistry, vol.98, issue.23, pp.27113561-13565, 1996.
DOI : 10.1007/BF00229111

C. Szabo, J. Mitchell, C. Thiemermann, and J. Vane, Nitric oxide-mediated hyporeactivity to noradrenaline precedes the induction of nitric oxide synthase in endotoxin shock, British Journal of Pharmacology, vol.26, issue.114
DOI : 10.1093/cvr/26.1.48

G. Theilmeier and M. Booke, Norepinephrine in septic patients--friend or foe? Journal of Clinical Anesthesia Clutter WE, Cryer PE: Plasma dose-response studies with noradrenaline and adrenaline in man, Prog Biochem Pharmacol, vol.15, issue.17, pp.154-15884, 1980.

B. Vallet, N. Lund, S. Curtis, D. Kelly, and S. Cain, Gut and muscle tissue PO2 in endotoxemic dogs during shock and resuscitation, Journal of Applied Physiology, vol.76, issue.2, pp.793-800, 1994.
DOI : 10.1152/jappl.1994.76.2.793

C. Ince and M. Sinaasappel, Microcirculatory oxygenation and shunting in sepsis and shock, Critical Care Medicine, vol.27, issue.7, pp.1369-1377, 1999.
DOI : 10.1097/00003246-199907000-00031

M. Dahn, P. Lange, K. Lobdell, B. Hans, L. Jacobs et al., Splanchnic and total body oxygen consumption differences in septic and injured patients, Surgery, vol.101, issue.1, pp.69-80, 1987.

D. Backer, D. Creteur, J. Noordally, O. Smail, N. Gulbis et al., Dependency Exist in Critically Ill Septic Patients?, American Journal of Respiratory and Critical Care Medicine, vol.62, issue.4, pp.1219-1225, 1998.
DOI : 10.1007/BF00254516

L. Gotloib, A. Shostak, P. Galdi, J. Jaichenko, and R. Fudin, Loss of microvascular negative charges accompanied by interstitial edema in septic rats' heart, Circ Shock, vol.36, issue.1, pp.45-56, 1992.

M. Solomon, R. Correa, H. Alexander, L. Koev, J. Cobb et al., Myocardial energy metabolism and morphology in a canine model of sepsis Structure-function relationships in the septic rat heart, Am J Physiol Am J Respir Crit Care Med, vol.266, issue.1565, pp.1473-1482, 1994.

J. Granton, C. Goddard, M. Allard, S. Van-eeden, and K. Walley, Leukocytes and decreased left-ventricular contractility during endotoxemia in rabbits., American Journal of Respiratory and Critical Care Medicine, vol.155, issue.6, pp.1977-1983, 1997.
DOI : 10.1164/ajrccm.155.6.9196105

L. Hinshaw, Sepsis/septic shock, Critical Care Medicine, vol.24, issue.6, pp.1072-1078, 1996.
DOI : 10.1097/00003246-199606000-00031

C. Rabuel, B. Tavernier, and A. , M: Physiopathologie de la défaillance cardiaque Springer 2005:51-71. 79. Rudiger A, Singer M: Mechanisms of sepsis-induced cardiac dysfunction, Crit Care Med, vol.35, issue.6, pp.1599-1608, 2007.
DOI : 10.1007/2-287-27496-0_3

S. Jones, M. Kovarik, and F. Romano, Cardiac and splenic norepinephrine turnover during septic peritonitis, American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, vol.250, issue.5, pp.892-897, 1986.
DOI : 10.1152/ajpregu.1986.250.5.R892

L. Wu, C. Tang, and M. Liu, HYPER- AND HYPOCARDIODYNAMIC STATES ARE ASSOCIATED WITH EXTERNALIZATION AND INTERNALIZATION, RESPECTIVELY, OF ??-ADRENERGIC RECEPTORS IN RAT HEART DURING SEPSIS, Shock, vol.7, issue.5, pp.318-323, 1997.
DOI : 10.1097/00024382-199705000-00002

C. Tang and M. Liu, Initial externalization followed by internalization of betaadrenergic receptors in rat heart during sepsis, Am J Physiol, vol.270, issue.1 2, pp.254-263, 1996.

B. Zlokovic, C. Zhang, D. Liu, J. Fernandez, and J. Griffin, Functional recovery after embolic stroke in rodents by activated protein C, Annals of Neurology, vol.280, issue.3, pp.474-477, 2005.
DOI : 10.1161/01.CIR.103.13.1799

T. Cheng, D. Liu, J. Griffin, J. Fernandez, F. Castellino et al., Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective, Nature Medicine, vol.102, issue.3, pp.338-342, 2003.
DOI : 10.1172/JCI2029

H. Isobe, K. Okajima, M. Uchiba, A. Mizutani, N. Harada et al., Activated Protein C Prevents Endotoxin-Induced Hypotension in Rats by Inhibiting Excessive Production of Nitric Oxide, Circulation, vol.104, issue.10, pp.1171-1175, 2001.
DOI : 10.1161/hc3501.093799

J. Hoffmann, B. Vollmar, M. Laschke, D. Inthorn, J. Fertmann et al., Microhemodynamic and cellular mechanisms of activated protein C action during endotoxemia*, Critical Care Medicine, vol.32, issue.4, pp.1011-1017, 2004.
DOI : 10.1097/01.CCM.0000120058.88975.42

T. Iba, A. Kidokoro, M. Fukunaga, K. Nagakari, A. Shirahama et al., Activated protein C improves the visceral microcirculation by attenuating the leukocyte-endothelial interaction in a rat lipopolysaccharide model, Critical Care Medicine, vol.33, issue.2, pp.368-372, 2005.
DOI : 10.1097/01.CCM.0000153415.04995.88

J. Nick, C. Coldren, M. Geraci, K. Poch, B. Fouty et al., Recombinant human activated protein C reduces human endotoxin-induced pulmonary inflammation via inhibition of neutrophil chemotaxis, Blood, vol.104, issue.13, pp.1043878-3885, 2004.
DOI : 10.1182/blood-2004-06-2140

K. Murakami, K. Okajima, M. Uchiba, M. Johno, T. Nakagaki et al., Activated protein C attenuates endotoxin-induced pulmonary vascular injury by inhibiting activated leukocytes in rats, Blood, vol.87, issue.2, pp.642-647, 1996.

I. Schoots, M. Levi, A. Van-vliet, A. Maas, E. Roossink et al., Inhibition of coagulation and inflammation by activated protein C or antithrombin reduces intestinal ischemia/reperfusion injury in rats, Critical Care Medicine, vol.32, issue.6, pp.321375-1383, 2004.
DOI : 10.1097/01.CCM.0000128567.57761.E9

L. Yamanel, M. Mas, B. Comert, A. Isik, S. Aydin et al., The effect of activated protein C on experimental acute necrotizing pancreatitis, Critical Care, vol.9, issue.3, pp.184-190, 2005.
DOI : 10.1186/cc3485

M. Riewald and W. Ruf, Protease-activated Receptor-1 Signaling by Activated Protein C in Cytokine-perturbed Endothelial Cells Is Distinct from Thrombin Signaling, Journal of Biological Chemistry, vol.12, issue.20, pp.19808-19814, 2005.
DOI : 10.1038/nm0402-349

N. Franscini, E. Bachli, N. Blau, M. Leikauf, A. Schaffner et al., Gene Expression Profiling of Inflamed Human Endothelial Cells and Influence of Activated Protein C, Circulation, vol.110, issue.18, pp.2903-2909, 2004.
DOI : 10.1161/01.CIR.0000146344.49689.BB

W. Hooper, D. Phillips, M. Renshaw, B. Evatt, and J. Benson, The up-regulation of IL- 6 and IL-8 in human endothelial cells by activated protein C, J Immunol, issue.5, pp.1612567-2573, 1998.

M. Brueckmann, A. Marx, H. Weiler, V. Liebe, S. Lang et al., Stabilization of monocyte chemoattractant protein- 1-mRNA by activated protein C, Thromb Haemost, vol.89, issue.1, pp.149-160, 2003.

B. White, M. Schmidt, C. Murphy, W. Livingstone, O. Toole et al., Activated protein C inhibits lipopolysaccharide-induced nuclear translocation of nuclear factor kappaB (NF-kappaB) and tumour necrosis factor alpha (TNF-alpha) production in the THP-1 monocytic cell line, British Journal of Haematology, vol.73, issue.1, pp.130-134, 2000.
DOI : 10.1074/jbc.272.28.17795

D. Joyce, L. Gelbert, A. Ciaccia, B. Dehoff, and B. Grinnell, Gene Expression Profile of Antithrombotic Protein C Defines New Mechanisms Modulating Inflammation and Apoptosis, Journal of Biological Chemistry, vol.95, issue.14, pp.27611199-11203, 2001.
DOI : 10.1093/glycob/4.2.221

D. Sturn, N. Kaneider, C. Feistritzer, A. Djanani, K. Fukudome et al., Expression and function of the endothelial protein C receptor in human neutrophils, Blood, vol.102, issue.4, pp.1499-1505, 2003.
DOI : 10.1182/blood-2002-12-3880

E. Wiel, M. Costecalde, G. Lebuffe, D. Corseaux, J. B. Bordet et al., Activated protein C increases sensitivity to vasoconstriction in rabbit Escherichia coli endotoxin-induced shock, Critical Care, vol.10, issue.2, p.47, 2006.
DOI : 10.1186/cc4858

URL : https://hal.archives-ouvertes.fr/inserm-00081194

J. Rodhin, S. Ap, . Sparks, and . Hv, Architecture of the vessel wall. Handbook of physiology. Section II: the Cardiovascular System II: Vascular Smooth Muscle, Bohr DF, pp.1-32, 1980.

. Murray, The Physiological Principle of Minimum Work: I. The Vascular System and the Cost of Blood Volume, Proceedings of the National Academy of Sciences, vol.12, issue.3, pp.207-214, 1926.
DOI : 10.1073/pnas.12.3.207

. Schretzenmayr, Uber kreislaufregulatorische Vorgäne an den grossen Arterien bei der Muskelarbeit. Plugers Arch, pp.743-748, 1933.

S. Rodbard and . Vascular-caliber, Vascular Caliber, Cardiology, vol.60, issue.1, pp.4-49, 1975.
DOI : 10.1159/000169701

S. Rodbard, Negative Feedback Mechanisms in the Architecture and Function of the Connective and Cardiovascular Tissues, Perspectives in Biology and Medicine, vol.13, issue.4, pp.507-527, 1970.
DOI : 10.1353/pbm.1970.0054

R. Furchgott and J. Zawadzki, The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine, Nature, vol.265, issue.5789, pp.373-376, 1980.
DOI : 10.1161/01.RES.34.3.317

P. Davies, Flow-mediated endothelial mechanotransduction, Physiological Reviews, vol.75, issue.3, pp.519-560, 1995.
DOI : 10.1152/physrev.1995.75.3.519

D. Henrion, Moyen d'étude des artéres de résistance Livre Biologie et pathologie du coeur et des vaisseaux, pp.419-426, 2002.

D. Annane, E. Bellissant, and J. Cavaillon, Septic shock, The Lancet, vol.365, issue.9453, pp.63-78, 2005.
DOI : 10.1016/S0140-6736(04)17667-8

URL : https://hal.archives-ouvertes.fr/hal-01414960

D. Remick, Pathophysiology of Sepsis, The American Journal of Pathology, vol.170, issue.5, pp.1435-1444, 2007.
DOI : 10.2353/ajpath.2007.060872

A. Rudiger and M. Singer, Mechanisms of sepsis-induced cardiac dysfunction, Critical Care Medicine, vol.35, issue.6, pp.1599-1608, 2007.
DOI : 10.1097/01.CCM.0000266683.64081.02

P. Pacher, J. Beckman, and L. Liaudet, Nitric Oxide and Peroxynitrite in Health and Disease, Physiological Reviews, vol.87, issue.1, pp.315-424, 2007.
DOI : 10.1089/152308601750100443

M. Rossi, M. Celes, and C. Prado, MYOCARDIAL STRUCTURAL CHANGES IN LONG-TERM HUMAN SEVERE SEPSIS/SEPTIC SHOCK MAY BE RESPONSIBLE FOR CARDIAC DYSFUNCTION, Shock, vol.27, issue.1, pp.10-18, 2007.
DOI : 10.1097/01.shk.0000235141.05528.47

G. Bernard, J. Vincent, and P. Laterre, Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis, New England Journal of Medicine, vol.344, issue.10, pp.699-709, 2001.
DOI : 10.1056/NEJM200103083441001

L. Mosnier, B. Zlokovic, and J. Griffin, The cytoprotective protein C pathway, Blood, vol.109, issue.8, pp.3161-3172, 2007.
DOI : 10.1182/blood-2006-09-003004

C. Esmon, The endothelial protein C receptor, Current Opinion in Hematology, vol.13, issue.5, pp.382-385, 2006.
DOI : 10.1097/01.moh.0000239712.93662.35

D. Joyce, L. Gelbert, and A. Ciaccia, Gene Expression Profile of Antithrombotic Protein C Defines New Mechanisms Modulating Inflammation and Apoptosis, Journal of Biological Chemistry, vol.95, issue.14, pp.11199-11203, 2001.
DOI : 10.1093/glycob/4.2.221

B. White, M. Schmidt, and C. Murphy, Activated protein C inhibits lipopolysaccharide-induced nuclear translocation of nuclear factor kappaB (NF-kappaB) and tumour necrosis factor alpha (TNF-alpha) production in the THP-1 monocytic cell line, British Journal of Haematology, vol.73, issue.1, pp.130-134, 2000.
DOI : 10.1074/jbc.272.28.17795

P. Bilbault, T. Lavaux, and A. Launoy, Influence of drotrecogin alpha (activated) infusion on the variation of Bax/Bcl-2 and Bax/Bcl-xl ratios in circulating mononuclear cells: A cohort study in septic shock patients, Critical Care Medicine, vol.35, issue.1, 2006.
DOI : 10.1097/01.CCM.0000251133.26979.F4

K. Yamaji, Y. Wang, and Y. Liu, Activated protein C, a natural anticoagulant protein, has antioxidant properties and inhibits lipid peroxidation and advanced glycation end products formation Bench-to-bedside review: The role of activated protein C in maintaining endothelial tight junction function and its relationship to organ injury):239. 14. Regnault V, Levy B. Recombinant activated protein C in sepsis: endothelium protection or endothelium therapy?, ):103. 15. Favory R, pp.319-325899, 2005.

H. Isobe, K. Okajima, and M. Uchiba, Activated Protein C Prevents Endotoxin-Induced Hypotension in Rats by Inhibiting Excessive Production of Nitric Oxide, Circulation, vol.104, issue.10, pp.1171-1175, 2001.
DOI : 10.1161/hc3501.093799

Z. Wang, F. Su, and P. Rogiers, Beneficial effects of recombinant human activated protein C in a ewe model of septic shock* Rapid and beneficial hemodynamic effects of activated protein C in septic shock patients Infiltration of inflammatory cells plays an important role in matrix metalloproteinase expression and activation in the heart during sepsis, Crit Care Med Intensive Care Med Am J Pathol, vol.31169, issue.205, pp.1573-15761567, 2005.

A. Chow, J. Cena, R. Schulz, S. Lancel, S. Tissier et al., Acute actions and novel targets of matrix metalloproteinases in the heart and vasculature Peroxynitrite decomposition catalysts prevent myocardial dysfunction and inflammation in endotoxemic rats, Br J Pharmacol J Am Coll Cardiol, vol.2243, issue.12, pp.2348-2358, 2004.

R. Ranaivo, H. Carusio, N. Wangensteen, and R. , Protection against endotoxic shock as a consequence of reduced nitrosative stress in MLCK210-null mice Superoxide production in vascular smooth muscle contributes to oxidative stress and impaired relaxation in atherosclerosis, Am J Pathol Circ Res, vol.17082, issue.2412, pp.439-4461298, 1998.

N. Sennoun, C. Montemont, and S. Gibot, Comparative effects of early versus delayed use of norepinephrine in resuscitated endotoxic shock The cytoprotective protein C pathway Activated Protein C ameliorates LPS-induced acute kidney injury and down-regulates renal iNOS and Angiotensin 2, Crit Care Med Blood Am J Physiol Renal Physiol Crit Care, vol.351099, issue.28, pp.1736-17403161, 2005.

D. Landry and J. Oliver, The Pathogenesis of Vasodilatory Shock, New England Journal of Medicine, vol.345, issue.8, pp.588-595, 2001.
DOI : 10.1056/NEJMra002709

C. Szabo, J. Mitchell, and C. Thiemermann, Nitric oxide-mediated hyporeactivity to noradrenaline precedes the induction of nitric oxide synthase in endotoxin shock, British Journal of Pharmacology, vol.26, issue.114, pp.786-792, 1993.
DOI : 10.1093/cvr/26.1.48

R. Huie, S. Padmaja, F. Soriano, L. Liaudet, and E. Szabo, The reaction of no with superoxide Resistance to acute septic peritonitis in poly(ADP-ribose) polymerase-1-deficient mice, Free Radic Res Commun Shock, vol.1817, issue.324, pp.195-199286, 1993.

J. John, A. Awab, and D. Norman, Activated protein C improves survival in severe sepsis patients with elevated troponin, Intensive Care Medicine, vol.353, issue.12, pp.2122-2128, 2007.
DOI : 10.1007/s00134-007-0816-7

M. Merx and C. Weber, Sepsis and the Heart, Circulation, vol.116, issue.7, pp.793-802, 2007.
DOI : 10.1161/CIRCULATIONAHA.106.678359

R. Rastaldo, P. Pagliaro, and S. Cappello, Nitric oxide and cardiac function Endotoxin-induced contractile dysfunction in guinea pig hearts is not mediated by nitric oxide Lipopolysaccharide induces oxidative cardiac mitochondrial damage and biogenesis Superoxide activates mitochondrial uncoupling proteins al. Association between mitochondrial dysfunction and severity and outcome of septic shock, Life Sci Am J Physiol Pt Cardiovasc Res Nature Lancet, vol.8126864415360, issue.3868679328, pp.779-793, 1995.

A. Mizutani, K. Okajima, and M. Uchiba, Activated protein C reduces ischemia/reperfusion-induced renal injury in rats by inhibiting leukocyte activation, Blood, vol.95, issue.12, pp.3781-3787, 2000.

J. Hoffmann, B. Vollmar, and M. Laschke, Microhemodynamic and cellular mechanisms of activated protein C action during endotoxemia*, Critical Care Medicine, vol.32, issue.4, pp.1011-1017, 2004.
DOI : 10.1097/01.CCM.0000120058.88975.42

Z. Galis, J. Khatri, M. Lalu, T. Csont, and R. Schulz, Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly Matrix metalloproteinase activities are altered in the heart and plasma during endotoxemia, Circ Res Crit Care Med, vol.9032, issue.436, pp.251-2621332, 2002.

J. Chen, C. Tung, and J. Allport, Near-infrared fluorescent imaging of matrix metalloproteinase activity after myocardial infarction Complexity of inducible nitric oxide synthase: cellular source determines benefit versus toxicity Expression and function of the endothelial protein C receptor in human neutrophils al. Endotoxemia and sepsis mortality reduction by non-anticoagulant activated protein C, Circulation Circulation Blood Kerschen EJ J Exp Med, vol.111108102204, issue.4710, pp.1800-18051107, 2003.

J. Griffin, J. Fernandez, and L. Mosnier, The promise of protein C Evaluation of endotoxin models for the study of sepsis Hemodynamic instability in sepsis: bedside assessment by Doppler echocardiography Early goal-directed therapy in the treatment of severe sepsis and septic shock, Blood Cells Mol Dis Shock Am J Respir Crit Care Med N Engl J Med, vol.3624168345, issue.4911, pp.211-2161270, 2001.

D. Landry and J. Oliver, The Pathogenesis of Vasodilatory Shock, New England Journal of Medicine, vol.345, issue.8, pp.588-595, 2001.
DOI : 10.1056/NEJMra002709

J. Russell, Management of Sepsis, New England Journal of Medicine, vol.355, issue.16, pp.1699-1713, 2006.
DOI : 10.1056/NEJMra043632

H. Galley and N. Webster, Physiology of the endothelium, British Journal of Anaesthesia, vol.93, issue.1, pp.105-118, 2004.
DOI : 10.1093/bja/aeh163

L. Mosnier, B. Zlokovic, and J. Griffin, The cytoprotective protein C pathway, Blood, vol.109, issue.8, pp.3161-72, 2007.
DOI : 10.1182/blood-2006-09-003004

K. Peters, R. Unger, J. Brunner, and C. Kirkpatrick, Molecular basis of endothelial dysfunction in sepsis, Cardiovascular Research, vol.60, issue.1, pp.49-57, 2003.
DOI : 10.1016/S0008-6363(03)00397-3

S. Orfanos, I. Mavrommati, I. Korovesi, and C. Roussos, Pulmonary endothelium in acute lung injury: from basic science to the critically ill, Intensive Care Med, vol.30, pp.1702-1714, 2004.

J. Stoclet, B. Muller, R. Andriantsitohaina, and A. Kleschyov, Overproduction of nitric oxide in pathophysiology of blood vessels, Biochemistry (Mosc), vol.63, pp.826-832, 1998.

O. 'brien, A. J. Wilson, R. Sibbald, M. Singer, and &. H. Clapp, Temporal variation in endotoxin-induced vascular hyporeactivity in a rat mesenteric artery organ culture model, British Journal of Pharmacology, vol.12, issue.3, pp.351-360, 2001.
DOI : 10.1111/j.1476-5381.1995.tb13343.x

J. Stoclet, M. Martinez, P. Ohlmann, S. Chasserot, C. Schott et al., Induction of Nitric Oxide Synthase and Dual Effects of Nitric Oxide and Cyclooxygenase Products in Regulation of Arterial Contraction in Human Septic Shock, Circulation, vol.100, issue.2, pp.107-112, 1999.
DOI : 10.1161/01.CIR.100.2.107

O. 'brien, L. Gupta, A. Grinnell, and B. , Activated protein C and sepsis, Frontiers in Bioscience, vol.11, issue.1, pp.676-98, 2006.
DOI : 10.2741/1827

R. Andriantsitohaina, V. Regnault, M. Slama, T. Lecompte, P. Lacolley et al., Activated protein C improves LPS-induced cardiovascular dysfunction by decreasing tissular inflammation and oxidative stress, Crit Care Med, 2008.

A. Gupta, D. Berg, B. Gerlitz, M. Richardson, E. Galbreath et al., ACTIVATED PROTEIN C SUPPRESSES ADRENOMEDULLIN AND AMELIORATES LIPOPOLYSACCHARIDE-INDUCED HYPOTENSION, Shock, vol.28, issue.4, pp.468-76, 2007.
DOI : 10.1097/SHK.0b013e3180487f09

E. Kerschen, J. Fernandez, and B. Cooley, Endotoxemia and sepsis mortality reduction by non-anticoagulant???activated protein C, The Journal of Experimental Medicine, vol.66, issue.10, pp.2439-2448, 2007.
DOI : 10.1097/01.shk.0000126906.52367.dd

D. E. Joyce, . Nelson, R. David, . Grinnell, and W. Brian, Leukocyte and endothelial cell interactions in sepsis: Relevance of the protein C pathway, Critical Care Medicine, vol.32, issue.Supplement, pp.280-86, 2004.
DOI : 10.1097/01.CCM.0000128037.72072.22

W. Aird, Phenotypic Heterogeneity of the Endothelium: II. Representative Vascular Beds, Circulation Research, vol.100, issue.2
DOI : 10.1161/01.RES.0000255690.03436.ae

F. Meziani, H. Kremer, A. Tesse, C. Baron-menguy, C. Mathien et al., Human Serum Albumin Improves Arterial Dysfunction during Early Resuscitation in Mouse Endotoxic Model via Reduced Oxidative and Nitrosative Stresses, The American Journal of Pathology, vol.171, issue.6
DOI : 10.2353/ajpath.2007.070316

URL : https://hal.archives-ouvertes.fr/hal-00207826

D. Joyce, L. Gelbert, and A. Ciaccia, Gene Expression Profile of Antithrombotic Protein C Defines New Mechanisms Modulating Inflammation and Apoptosis, Journal of Biological Chemistry, vol.95, issue.14, pp.11199-11203, 2001.
DOI : 10.1093/glycob/4.2.221

B. White, M. Schmidt, and C. Murphy, Activated protein C inhibits lipopolysaccharide-induced nuclear translocation of nuclear factor kappaB (NF-kappaB) and tumour necrosis factor alpha (TNF-alpha) production in the THP-1 monocytic cell line, British Journal of Haematology, vol.73, issue.1, pp.130-134, 2000.
DOI : 10.1074/jbc.272.28.17795

P. Bilbault, T. Lavaux, and A. Launoy, Influence of drotrecogin alpha (activated) infusion on the variation of Bax/Bcl-2 and Bax/Bcl-xl ratios in circulating mononuclear cells: A cohort study in septic shock patients, Critical Care Medicine, vol.35, issue.1, pp.69-75, 2007.
DOI : 10.1097/01.CCM.0000251133.26979.F4

K. Yamaji, Y. Wang, and Y. Liu, Activated protein C, a natural anticoagulant protein, has antioxidant properties and inhibits lipid peroxidation and advanced glycation end products formation, Thrombosis Research, vol.115, issue.4
DOI : 10.1016/j.thromres.2004.09.011

M. Looney and M. Matthay, Bench-to-bedside review: The role of activated protein C in maintaining endothelial tight junction function and its relationship to organ injury, Critical Care, vol.10, issue.6, p.239, 2006.
DOI : 10.1186/cc5099

V. Regnault and B. Levy, Recombinant activated protein C in sepsis: endothelium protection or endothelium therapy? Crit Care, p.103, 2007.

C. Esmon, The endothelial protein C receptor, Current Opinion in Hematology, vol.13, issue.5, pp.382-385, 2006.
DOI : 10.1097/01.moh.0000239712.93662.35

R. Favory, S. Lancel, X. Maréchal, S. Tissier, and R. Neviere, Cardiovascular protective role for activated protein C during endotoxemia in rats, Intensive Care Medicine, vol.95, issue.6, pp.899-905, 2006.
DOI : 10.1056/NEJM198908033210503

Z. Wang, F. Su, P. Rogiers, and J. Vincent, Beneficial effects of recombinant human activated protein C in a ewe model of septic shock*, Critical Care Medicine, vol.35, issue.11, pp.2594-600, 2007.
DOI : 10.1097/01.CCM.0000287590.55294.40

X. Monnet, B. Lamia, and N. Anguel, Rapid and beneficial hemodynamic effects of activated protein C in septic shock patients, Intensive Care Medicine, vol.33, issue.11, pp.1573-1576, 2005.
DOI : 10.1007/s00134-003-1731-1

S. Moncada and E. Higgs, Endogenous nitric oxide: physiology, pathology and clinical relevance, European Journal of Clinical Investigation, vol.8, issue.4, pp.361-74, 1991.
DOI : 10.1097/00000441-189305000-00001

D. Dudzinski and T. Michel, Life history of eNOS: Partners and pathways, Cardiovascular Research, vol.75, issue.2, pp.247-60, 2007.
DOI : 10.1016/j.cardiores.2007.03.023

S. Chauhan, G. Seggara, P. Vo, R. Macallister, A. Hobbs et al., Protection against lipopolysaccharide-induced endothelial dysfunction in resistance and conduit vasculature of iNOS knockout mice, The FASEB Journal, vol.17, issue.6, pp.773-778, 2003.
DOI : 10.1096/fj.02-0668fje

N. Matsuda, Y. Hayashi, Y. Takahashi, and Y. Hattori, Phosphorylation of Endothelial Nitric-Oxide Synthase Is Diminished in Mesenteric Arteries from Septic Rabbits Depending on the Altered Phosphatidylinositol 3-Kinase/Akt Pathway: Reversal Effect of Fluvastatin Therapy, Journal of Pharmacology and Experimental Therapeutics, vol.319, issue.3
DOI : 10.1124/jpet.106.109785

M. Brueckmann, S. Horn, S. Lang, K. Fukudome, S. Nahrup et al., Recombinant human activated protein C upregulates cyclooxygenase-2 expression in endothelial cells via binding to endothelial cell protein C receptor and activation of protease-activated receptor-1, Thrombosis and Haemostasis, vol.93, issue.4, pp.743-50, 2005.
DOI : 10.1160/TH04-08-0511

D. Martin, R. Hoeth, M. Hofer-warbinek, R. Schmid, and J. , The Transcription Factor NF-??B and the Regulation of Vascular Cell Function, Arteriosclerosis, Thrombosis, and Vascular Biology, vol.20, issue.11, pp.83-91, 2000.
DOI : 10.1161/01.ATV.20.11.e83

E. Abraham, Nuclear factor-kappaB and its role in sepsis-associated organ failure

A. Kumar, E. Schupp, E. Bubbel, A. Ali, B. Milcarek et al., Cardiovascular response to dobutamine stress predicts outcome in severe sepsis and septic shock, Critical Care, vol.12, issue.2, p.35, 2008.
DOI : 10.1186/cc6814

B. Vallet, C. Chopin, S. Curtis, B. Dupuis, F. Fourrier et al., Prognostic value of the dobutamine test in patients with sepsis syndrome and normal lactate values, Critical Care Medicine, vol.21, issue.12, pp.1868-1875, 1993.
DOI : 10.1097/00003246-199312000-00014

A. Rhodes, F. Lamb, I. Malagon, P. Newman, R. Grounds et al., A prospective study of the use of a dobutamine stress test to identify outcome in patients with sepsis, severe sepsis, or septic shock, Critical Care Medicine, vol.27, issue.11, pp.2361-2366, 1999.
DOI : 10.1097/00003246-199911000-00007

W. Jellema, A. Groeneveld, K. Wesseling, L. Thijs, N. Westerhof et al., Heterogeneity and prediction of hemodynamic responses to dobutamine in patients with septic shock, Critical Care Medicine, vol.34, issue.9, pp.2392-2398, 2006.
DOI : 10.1097/01.CCM.0000233871.52553.CD

D. Landry and J. Oliver, The Pathogenesis of Vasodilatory Shock, New England Journal of Medicine, vol.345, issue.8, pp.588-595, 2001.
DOI : 10.1056/NEJMra002709

P. Pacher, J. Beckman, and L. Liaudet, Nitric Oxide and Peroxynitrite in Health and Disease, Physiological Reviews, vol.87, issue.1, pp.315-424, 2007.
DOI : 10.1089/152308601750100443

B. Levy, B. Dusang, D. Annane, S. Gibot, and P. Bollaert, Cardiovascular response to dopamine and early prediction of outcome in septic shock: A prospective multiple-center study*, Critical Care Medicine, vol.33, issue.10, pp.2172-2177, 2005.
DOI : 10.1097/01.CCM.0000181297.14319.3C

B. Levy, S. Gibot, P. Franck, A. Cravoisy, and P. Bollaert, Relation between muscle Na+K+ ATPase activity and raised lactate concentrations in septic shock: a prospective study, The Lancet, vol.365, issue.9462, pp.871-875, 2005.
DOI : 10.1016/S0140-6736(05)71045-X

B. Levy, O. Desebbe, C. Montemont, and S. Gibot, Increased aerobic glycolysis through beta-2 stimulation is a common mechanism involved in lactate formation during shock states, Shock, 2008.

J. Levraut, C. Ichai, I. Petit, J. Ciebiera, O. Perus et al., Low exogenous lactate clearance as an early predictor of mortality in normolactatemic critically ill septic patients, Critical Care Medicine, vol.31, issue.3, pp.705-710, 2003.
DOI : 10.1097/01.CCM.0000045561.85810.45

G. Bernard, J. Vincent, and P. Laterre, Efficacy and Safety of Recombinant Human Activated Protein C for Severe Sepsis, New England Journal of Medicine, vol.344, issue.10, pp.699-709, 2001.
DOI : 10.1056/NEJM200103083441001

X. Monnet, B. Lamia, N. Anguel, C. Richard, G. Bonmarchand et al., Rapid and beneficial hemodynamic effects of activated protein C in septic shock patients, Intensive Care Medicine, vol.33, issue.11, pp.1573-1579, 2005.
DOI : 10.1007/s00134-003-1731-1

A. Kalil, S. Coyle, and J. Um, Effects of Drotrecogin Alfa (Activated) in Human Endotoxemia, Shock, vol.21, issue.3, pp.222-231, 2004.
DOI : 10.1097/01.shk.0000116778.27924.79

U. Derhaschnig, R. Reiter, P. Knobl, M. Baumgartner, P. Keen et al., Recombinant human activated protein C (rhAPC; drotrecogin alfa [activated]) has minimal effect on markers of coagulation, fibrinolysis, and inflammation in acute human endotoxemia, Blood, vol.102, issue.6, pp.2093-2101, 2003.
DOI : 10.1182/blood-2003-02-0416

H. Isobe, K. Okajima, and M. Uchiba, Activated Protein C Prevents Endotoxin-Induced Hypotension in Rats by Inhibiting Excessive Production of Nitric Oxide, Circulation, vol.104, issue.10, pp.1171-1176, 2001.
DOI : 10.1161/hc3501.093799

R. Favory, S. Lancel, X. Marechal, S. Tissier, and R. Neviere, Cardiovascular protective role for activated protein C during endotoxemia in rats, Intensive Care Medicine, vol.95, issue.6, pp.899-905, 2006.
DOI : 10.1056/NEJM198908033210503

S. Sennoun, . Do, D. Barraud, S. Gibot, and B. Levy, Hemodynamic effects of activated protein C, Intensive Care Medicine, vol.32, p.74, 2006.

J. Nick, C. Coldren, and M. Geraci, Recombinant human activated protein C reduces human endotoxin-induced pulmonary inflammation via inhibition of neutrophil chemotaxis, Blood, vol.104, issue.13, pp.3878-85, 2004.
DOI : 10.1182/blood-2004-06-2140

E. Abraham, Effects of Recombinant Human Activated Protein C in Human Models of Endotoxin Administration, Proceedings of the American Thoracic Society, vol.2, issue.3, pp.243-250, 2005.
DOI : 10.1513/pats.200501-004AC

B. Dahlback and B. Villoutreix, Regulation of Blood Coagulation by the Protein C Anticoagulant Pathway: Novel Insights Into Structure-Function Relationships and Molecular Recognition, Arteriosclerosis, Thrombosis, and Vascular Biology, vol.25, issue.7, pp.1311-1331, 2005.
DOI : 10.1161/01.ATV.0000168421.13467.82

W. Macias, S. Yan, and M. Williams, New insights into the protein C pathway: potential implications for the biological activities of drotrecogin alfa (activated), Critical Care, vol.9, issue.Suppl 4, pp.38-45, 2005.
DOI : 10.1186/cc3747

B. Dahlback and B. Villoutreix, The anticoagulant protein C pathway, FEBS Letters, vol.276, issue.15, pp.3310-3316, 2005.
DOI : 10.1074/jbc.M006541200

A. Mizutani, K. Okajima, M. Uchiba, and T. Noguchi, Activated protein C reduces ischemia/reperfusion-induced renal injury in rats by inhibiting leukocyte activation, Blood, vol.95, pp.3781-3788, 2000.

J. Hoffmann, B. Vollmar, and M. Laschke, Microhemodynamic and cellular mechanisms of activated protein C action during endotoxemia*, Critical Care Medicine, vol.32, issue.4, pp.1011-1018, 2004.
DOI : 10.1097/01.CCM.0000120058.88975.42

M. Uchiba, K. Okajima, and Y. Oike, Activated Protein C Induces Endothelial Cell Proliferation by Mitogen-Activated Protein Kinase Activation In Vitro and Angiogenesis In Vivo, Circulation Research, vol.95, issue.1, pp.34-41, 2004.
DOI : 10.1161/01.RES.0000133680.87668.FA

H. Isobe, K. Okajima, N. Harada, W. Liu, and H. Okabe, Activated protein C reduces stress-induced gastric mucosal injury in rats by inhibiting the endothelial cell injury, Journal of Thrombosis and Haemostasis, vol.95, issue.2, pp.313-333, 2004.
DOI : 10.1023/A:1012779530004

D. Raulet, Innate immune recognition by stimulatory immunoreceptors, Curr Opin Immunol, vol.15, pp.37-44, 2003.

H. Kubagawa, P. Burrows, and M. Cooper, A novel pair of immunoglobulin-like receptors expressed by B cells and myeloid cells, Proceedings of the National Academy of Sciences, vol.272, issue.11, pp.5261-5267, 1997.
DOI : 10.1074/jbc.272.11.7320

C. Cantoni, C. Bottino, and M. Vitale, NKp44, A Triggering Receptor Involved in Tumor Cell Lysis by Activated Human Natural Killer Cells, Is a Novel Member of the Immunoglobulin Superfamily, The Journal of Experimental Medicine, vol.159, issue.5, pp.787-96, 1999.
DOI : 10.1002/eji.1830270313

J. Dietrich, M. Cella, M. Seiffert, H. Buhring, and M. Colonna, Cutting Edge: Signal-Regulatory Protein ??1 Is a DAP12-Associated Activating Receptor Expressed in Myeloid Cells, The Journal of Immunology, vol.164, issue.1, pp.9-12, 2000.
DOI : 10.4049/jimmunol.164.1.9

A. Bouchon, J. Dietrich, and M. Colonna, Cutting Edge: Inflammatory Responses Can Be Triggered by TREM-1, a Novel Receptor Expressed on Neutrophils and Monocytes, The Journal of Immunology, vol.164, issue.10, pp.4991-4996, 2000.
DOI : 10.4049/jimmunol.164.10.4991

M. Daws, L. Lanier, W. Seaman, and J. Ryan, Cloning and characterization of a novel mouse myeloid DAP12-associated receptor family, European Journal of Immunology, vol.126, issue.3
DOI : 10.1016/0003-2697(82)90118-X

A. Bouchon, F. Facchetti, M. Weigand, and M. Colonna, TREM-1 amplifies inflammation and is a crucial mediator of septic shock, Nature, vol.410, issue.6832, pp.1103-1110, 2001.
DOI : 10.1038/35074114

M. Colonna and F. Facchetti, TREM???1 (Triggering Receptor Expressed on Myeloid Cells): A New Player in Acute Inflammatory Responses, The Journal of Infectious Diseases, vol.21, issue.s2, pp.397-401, 2003.
DOI : 10.1182/blood-2002-02-0523

J. Bleharski, V. Kiessler, and C. Buonsanti, A Role for Triggering Receptor Expressed on Myeloid Cells-1 in Host Defense During the Early-Induced and Adaptive Phases of the Immune Response, The Journal of Immunology, vol.170, issue.7, pp.3812-3820, 2003.
DOI : 10.4049/jimmunol.170.7.3812

M. Radsak, H. Salih, H. Rammensee, and H. Schild, Triggering Receptor Expressed on Myeloid Cells-1 in Neutrophil Inflammatory Responses: Differential Regulation of Activation and Survival, The Journal of Immunology, vol.172, issue.8, pp.4956-63, 2004.
DOI : 10.4049/jimmunol.172.8.4956

S. Knapp, S. Gibot, A. De-vos, H. Versteeg, M. Colonna et al., Cutting Edge: Expression Patterns of Surface and Soluble Triggering Receptor Expressed on Myeloid Cells-1 in Human Endotoxemia, The Journal of Immunology, vol.173, issue.12, pp.7131-7135, 2004.
DOI : 10.4049/jimmunol.173.12.7131

S. Gibot, M. Kolopp-sarda, and M. Bene, A Soluble Form of the Triggering Receptor Expressed on Myeloid Cells-1 Modulates the Inflammatory Response in Murine Sepsis, The Journal of Experimental Medicine, vol.10, issue.11, pp.1419-1445, 2004.
DOI : 10.7326/0003-4819-141-1-200407060-00009

S. Gibot, A. Cravoisy, B. Levy, M. Bene, G. Faure et al., Soluble Triggering Receptor Expressed on Myeloid Cells and the Diagnosis of Pneumonia, New England Journal of Medicine, vol.350, issue.5, pp.451-459, 2004.
DOI : 10.1056/NEJMoa031544

R. Determann, J. Millo, and S. Gibot, Serial changes in soluble TREM-1 Pathway Modulation during Pneumonia ? JID) ? 983 triggering receptor expressed on myeloid cells in the lung during development of ventilator-associated pneumonia, Intensive Care Med, vol.194, issue.31, pp.1495-500, 2005.

L. Richeldi, M. Mariani, and M. Losi, Triggering receptor expressed on myeloid cells: role in the diagnosis of lung infections, European Respiratory Journal, vol.24, issue.2, pp.247-50, 2004.
DOI : 10.1183/09031936.04.00014204

T. Schagat, J. Wofford, K. Greene, and J. Wright, Surfactant protein A differentially regulates peripheral and inflammatory neutrophil chemotaxis, American Journal of Physiology-Lung Cellular and Molecular Physiology, vol.264, issue.1, pp.140-147, 2003.
DOI : 10.1152/ajplung.1993.264.4.L338

S. Boyer, K. Faure, and F. Ader, Chronic pneumonia with Pseudomonas aeruginosa and impaired alveolar fluid clearance, Respiratory Research, vol.116, issue.1, p.17, 2005.
DOI : 10.1378/chest.116.1.157

A. Gunther, P. Mosavi, and S. Heinemann, Alveolar Fibrin Formation Caused by Enhanced Procoagulant and Depressed Fibrinolytic Capacities in Severe Pneumonia, American Journal of Respiratory and Critical Care Medicine, vol.151, issue.2, pp.454-62, 2000.
DOI : 10.1016/0140-6736(93)92004-D

M. Levi, M. Schultz, A. Rijneveld, and T. Van-der-poll, Bronchoalveolar coagulation and fibrinolysis in endotoxemia and pneumonia, Critical Care Medicine, vol.31, issue.Supplement, pp.238-280, 2003.
DOI : 10.1097/01.CCM.0000057849.53689.65

H. Nochi, N. Aoki, and K. Oikawa, Modulation of Hepatic Granulomatous Responses by Transgene Expression of DAP12 or TREM-1-Ig Molecules, The American Journal of Pathology, vol.162, issue.4, pp.1191-201, 2003.
DOI : 10.1016/S0002-9440(10)63915-6

I. Turnbull, J. Mcdunn, T. Takai, R. Townsend, J. Cobb et al., DAP12 (KARAP) amplifies inflammation and increases mortality from endotoxemia and septic peritonitis, The Journal of Experimental Medicine, vol.10, issue.3, pp.363-372, 2005.
DOI : 10.1021/ac026136s

URL : http://jem.rupress.org/content/jem/202/3/363.full.pdf

J. Hamerman, N. Tchao, C. Lowell, and L. Lanier, Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12, Nature Immunology, vol.19, issue.6, pp.579-86, 2005.
DOI : 10.1016/S0022-1759(98)00204-X

K. Carpenter, K. Buckland, Z. Xing, and C. Hogaboam, Intrapulmonary, Adenovirus-Mediated Overexpression of KARAP/DAP12 Enhances Fungal Clearance during Invasive Aspergillosis, Infection and Immunity, vol.73, issue.12, pp.8402-8408, 2005.
DOI : 10.1128/IAI.73.12.8402-8406.2005

E. Pishko, G. Kirimanjeswara, M. Pilione, L. Gopinathan, M. Kennett et al., Antibody-mediated bacterial clearance from the lower respiratory tract of mice requires complement component C3, European Journal of Immunology, vol.34, issue.1, pp.184-93, 2004.
DOI : 10.1002/eji.200324234

M. Levi and T. Van-der-poll, Two-Way Interactions Between Inflammation and Coagulation, Trends in Cardiovascular Medicine, vol.15, issue.7, pp.254-263, 2005.
DOI : 10.1016/j.tcm.2005.07.004