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Intensive Care Medicine
Published in: Intensive Care Medicine 12/2007

01-12-2007 | Editorial

Recombinant human activated protein C in experimental models of acute lung injury: the timing is critical!

Authors: Corinna Velik-Salchner, Volker Wenzel, Dirk M. Maybauer, Marc O. Maybauer

Published in: Intensive Care Medicine | Issue 12/2007

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Excerpt

The current understanding of the pathophysiology of sepsis is that inflammation, coagulation, and apoptosis are linked throughout the disease process [1]. Recombinant human activated protein C (rhAPC), a natural anticoagulant, is the first biological agent to have shown a significant survival benefit in patients with sepsis [2]. The protective effect of rhAPC in septic patients may reflect the ability of rhAPC to modulate multiple pathways. In addition to its anticoagulant properties, rhAPC down-regulates inflammatory and apoptotic responses [1] and, therefore, may be interesting to treat a pathophysiology with a systemic inflammatory response, such as acute lung injury. …
Literature
1.
Liaw PC (2004) Endogenous protein C activation in patients with severe sepsis. Crit Care Med 32:S214–S218PubMedCrossRef
2.
Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ Jr (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699–709PubMedCrossRef
3.
Richard J-C, Bregeon F, Leray V, Le Bars D, Costes N, Tourvieille C, Lavenne F, Devouassoux-Shisheboran M, Gimenez G, Guerin C (2007) Effect of activated protein C on pulmonary blood flow and cytokine production in experimental acute lung injury. Intensive Care Med DOI 10.​1007/​s00134-007-0782-0
4.
Schuster DP (1994) ARDS: clinical lessons from the oleic acid model of acute lung injury. Am J Respir Crit Care Med 149:245–260PubMed
5.
Rosenthal C, Caronia C, Quinn C, Lugo N, Sagy M (1998) A comparison among animal models of acute lung injury. Crit Care Med 26:912–916PubMedCrossRef
6.
Hill LL, Chen DL, Kozlowski J, Schuster DP (2004) Neutrophils and neutrophil products do not mediate pulmonary hemodynamic effects of endotoxin on oleic acid-induced lung injury. Anesth Analg 98:452–457PubMedCrossRef
7.
Gust R, Kozlowski J, Stephenson AH, Schuster DP (1998) Synergistic hemodynamic effects of low-dose endotoxin and acute lung injury. Am J Respir Crit Care Med 157:1919–1926PubMed
8.
Chen DL, Schuster DP (2004) Positron emission tomography with [18F]fluorodeoxyglucose to evaluate neutrophil kinetics during acute lung injury. Am J Physiol Lung Cell Mol Physiol 286:L834–840PubMedCrossRef
9.
Jian MY, Koizumi T, Tsushima K, Fujimoto K, Kubo K (2005) Activated protein C attenuates acid-aspiration lung injury in rats. Pulm Pharmacol Ther 18:291–296PubMedCrossRef
10.
Murakami K, Okajima K, Uchiba M, Johno M, Nakagaki T, Okabe H, Takatsuki K (1996) Activated protein C attenuates endotoxin-induced pulmonary vascular injury by inhibiting activated leukocytes in rats. Blood 87:642–647PubMed
11.
Murakami K, Okajima K, Uchiba M, Johno M, Nakagaki T, Okabe H, Takatsuki K (1997) Activated protein C prevents LPS-induced pulmonary vascular injury by inhibiting cytokine production. Am J Physiol 272:L197–202PubMed
12.
Sturn DH, Kaneider NC, Feistritzer C, Djanani A, Fukudome K, Wiedermann CJ (2003) Expression and function of the endothelial protein C receptor in human neutrophils. Blood 102:1499–1505PubMedCrossRef
13.
Nick JA, Coldren CD, Geraci MW, Poch KR, Fouty BW, O'Brien J, Gruber M, Zarini S, Murphy RC, Kuhn K, Richter D, Kast KR, Abraham E (2004) Recombinant human activated protein C reduces human endotoxin-induced pulmonary inflammation via inhibition of neutrophil chemotaxis. Blood 104:3878–3885PubMedCrossRef
14.
Maybauer MO, Maybauer DM, Fraser JF, Traber LD, Westphal M, Enkhbaatar P, Cox RA, Huda R, Hawkins HK, Morita N, Murakami K, Mizutani A, Herndon DN, Traber DL (2006) Recombinant human activated protein C improves pulmonary function in ovine acute lung injury resulting from smoke inhalation and sepsis. Crit Care Med 34:2432–2438PubMedCrossRef
15.
Robriquet L, Collet F, Tournoys A, Prangere T, Neviere R, Fourrier F, Guery BP (2006) Intravenous administration of activated protein C in Pseudomonas-induced lung injury: impact on lung fluid balance and the inflammatory response. Respir Res 7:41PubMedCrossRef
16.
Tomashefski JF Jr (2000) Pulmonary pathology of acute respiratory distress syndrome. Clin Chest Med 21:435–466PubMedCrossRef
17.
Gunther A, Mosavi P, Heinemann S, Ruppert C, Muth H, Markart P, Grimminger F, Walmrath D, Temmesfeld-Wollbruck B, Seeger W (2000) Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia. Comparison with the acute respiratory distress syndrome. Am J Respir Crit Care Med 161:454–462PubMed
18.
Traber DL, Herndon DN, Enkhbaatar P, Maybauer MO, Maybauer DM (2007) The pathophysiology of inhalation injury. In: Herndon DN (ed.) Total burn care. Saunders, London, pp. 248–261
19.
Eichacker PQ, Natanson C, Danner RL (2006) Surviving sepsis – practice guidelines, marketing campaigns, and Eli Lilly. N Engl J Med 355:1640–1642PubMedCrossRef
Metadata
Title
Recombinant human activated protein C in experimental models of acute lung injury: the timing is critical!
Authors
Corinna Velik-Salchner
Volker Wenzel
Dirk M. Maybauer
Marc O. Maybauer
Publication date
01-12-2007
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 12/2007
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-007-0783-z

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