Nebulized anticoagulants limit pulmonary coagulopathy, but not inflammation, in a model of experimental lung injury

Journal of Aerosol Medicine and Pulmonary Drug Delivery

Volumn 23, Issue 2, 2010, Pages 105-111

  Hofstra, Jorrit J ^a   Vlaar, Alexander P ^a   Cornet, Alexander D ^a   Dixon, Barry ^b   Roelofs, Joris J ^a   Choi, Goda ^a   Van Der Poll, Tom ^a   Levi, Marcel ^a   Schultz, Marcus J ^a  

^a UNIVERSITY OF AMSTERDAM   (Netherlands)

^b ST VINCENT S HOSPITAL   (Australia)

Author keywords

Activated protein C; Acute lung injury; Administration by inhalation; Antithrombin; Danaparoid; Heparin

Indexed keywords

ANTICOAGULANT AGENT; ANTITHROMBIN; CYTOKINE INDUCED NEUTROPHIL CHEMOATTRACTANT; DANAPAROID; DROTRECOGIN; FIBRIN; HEPARIN; INTERLEUKIN 6; LIPOPOLYSACCHARIDE; MYELOPEROXIDASE; PLACEBO; SODIUM CHLORIDE; TUMOR NECROSIS FACTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD CLOTTING DISORDER; CONTROLLED STUDY; DRUG INHIBITION; DRUG MECHANISM; HISTOPATHOLOGY; INFLAMMATION; LUNG INJURY; MALE; NEBULIZATION; NONHUMAN; RAT;

ADMINISTRATION, INHALATION; ANIMALS; ANTICOAGULANTS; BLOOD COAGULATION DISORDERS; BRONCHOALVEOLAR LAVAGE FLUID; DISEASE MODELS, ANIMAL; ENDOTOXEMIA; HEMOSTASIS; INFLAMMATION; LIPOPOLYSACCHARIDES; LUNG; LUNG INJURY; MALE; NEBULIZERS AND VAPORIZERS; RATS; RATS, SPRAGUE-DAWLEY;

EID: 77951094607     PISSN: 19412711     EISSN: 19412703     Source Type: Journal    
DOI: 10.1089/jamp.2009.0779     Document Type: Article

References (28)

1. Levi M, and Ten Cate H: Disseminated intravascular coagulation. N Engl J Med. 1999;341:586-592.
2. Warren BL, Eid A, Singer P, Pillay SS, Carl P, Novak I, Chalupa P, Atherstone A, Pénzes I, Kübler A, Knaub S, Keinecke HO, Heinrichs H, Schindel F, Juers M, Bone RC, Opal SM, and KyberSept Trial Study Group: Caring for the critically ill patient. High-dose antithrombin III in severe sepsis: a randomized controlled trial. JAMA. 2001;286:1869-1878.
3. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ, and Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Study Group: Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344:699-709.
4. Ware LB, and Matthay MA: The acute respiratory distress syndrome. N Engl J Med. 2000;342:1334-1349.
5. Günther A, Mosavi P, Heinemann S, Ruppert C, Muth H, Markart P, Grimminger F, Walmrath D, Temmesfeld-Wollbrück B, and SeegerW: 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. 2000;161:454-462.
6. van der Poll T, Levi M, Nick JA, and Abraham E: Activated protein C inhibits local coagulation after intrapulmonary delivery of endotoxin in humans. Am J Respir Crit Care Med. 2005;171:1125-1128.
7. Vincent JL, Angus DC, Artigas A, Kalil A, Basson BR, Jamal HH, Johnson G, Bernard GR, and Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Study Group: Effects of drotrecogin alfa (activated) on organ dysfunction in the PROWESS trial. Crit Care Med. 2003;31:834-840.
8. Murakami K, Okajima K, Uchiba M, Johno M, Nakagaki T, Okabe H, and Takatsuki K: Activated protein C prevents LPS-induced pulmonary vascular injury by inhibiting cytokine production. Am J Physiol. 1997;272:L197-L202.
9. Liu KD, Levitt J, Zhuo H, Kallet RH, Brady S, Steingrub J, Tidswell M, Siegel MD, Soto G, Peterson MW, Chesnutt MS, Phillips C, Weinacker A, Thompson BT, Eisner MD, and Matthay MA: Randomized clinical trial of activated protein C for the treatment of acute lung injury. Am J Respir Crit Care Med. 2008;178:618-623.
10. Eisele B, Lamy M, Thijs LG, Keinecke HO, Schuster HP, Matthias FR, Fourrier F, Heinrichs H, and Delvos U: Antithrombin III in patients with severe sepsis. A randomized, placebo-controlled, double-blind multicenter trial plus a meta-analysis on all randomized, placebo-controlled, double-blind trials with antithrombin III in severe sepsis. Intensive Care Med. 1998;24:663-672.
11. Jaimes F, De La Rosa G, Morales C, Fortich F, Arango C, Aguirre D, and Muñoz A: Unfractioned heparin for treatment of sepsis: a randomized clinical trial (The HETRASE Study). Crit Care Med. 2009;37:1185-1196.
12. DesaiMH,MlcakR,Richardson J,NicholsR, andHerndonDN: Reduction in mortality in pediatric patients with inhalation injury with aerosolized heparin=N-acetylcystine [correction of acetylcystine] therapy. J Burn Care Rehabil. 1998;19:210-212.
13. Choi G, Hofstra JJ, Roelofs JJ, Rijneveld AW, Bresser P, van der Zee JS, Florquin S, van der Poll T, Levi M, and Schultz MJ: Antithrombin inhibits bronchoalveolar activation of coagulation and limits lung injury during Streptococcus pneumoniae pneumonia in rats. Crit Care Med. 2008;36:204-210.
14. Choi G, Vlaar APJ, Schouten M, Van't Veer C, van der Poll T, Levi M, and Schultz MJ: Natural anticoagulants limit lipopolysaccharide-induced pulmonary coagulation but not inflammation. Eur Respir J. 2007;30:423-428.
15. Choi G, Hofstra JJ, Roelofs JJ, Florquin S, Bresser P, Levi M, van der Poll T, and Schultz MJ: Recombinant human activated protein C inhibits local and systemic activation of coagulation without influencing inflammation during Pseudomonas aeruginosa pneumonia in rats. Crit Care Med. 2007; 35:1362-1368.
16. Hoffmann JN, Vollmar B, Laschke MW, Inthorn D, Kaneider NC, Dunzendorfer S, Wiedermann CJ, Römisch J, Schildberg FW, and Menger MD: Adverse effect of heparin on antithrombin action during endotoxemia: microhemodynamic and cellular mechanisms. Thromb Haemost. 2002;88:242-252.
17. Hagiwara S, Iwasaka H, Hidaka S, Hishiyama S, and Noguchi T: Danaparoid sodium inhibits systemic inflammation and prevents endotoxin-induced acute lung injury in rats. Crit Care. 2008;12:R43.
18. Levi M, de Boer JP, Roem D, ten Cate JW, and Hack CE: Plasminogen activation in vivo upon intravenous infusion of DDAVP. Quantitative assessment of plasmin-alpha 2- antiplasmin complexwith a novelmonoclonal antibody based radioimmunoassay. Thromb Haemost. 1992;67:111-116.
19. Knapp S, Wieland CW, van 't Veer C, Takeuchi O, Akira S, Florquin S, and van der Poll T: Toll-like receptor 2 plays a role in the early inflammatory response to murine pneumococcal pneumonia but does not contribute to antibacterial defense. J Immunol. 2004;172:3132-3138.
20. Giebler R, Schmidt U, Koch S, Peters J, and Scherer R: Combined antithrombin III and C1-esterase inhibitor treatment decreases intravascular fibrin deposition and attenuates cardiorespiratory impairment in rabbits exposed to Escherichia coli endotoxin. Crit Care Med. 1999;27:597-604.
21. Okajima K: Antithrombin prevents endotoxin-induced pulmonary vascular injury by inhibiting leukocyte activation. Blood Coagul Fibrinolysis. 1998;9(Suppl 2):S25-S37.
22. Yasui H, Gabazza EC, Tamaki S, Kobayashi T, Hataji O, Yuda H, Shimizu S, Suzuki K, Adachi Y, and Taguchi O: Intratracheal administration of activated protein C inhibits bleomycin-induced lung fibrosis in the mouse. Am J Respir Crit Care Med. 2001;163:1660-1668.
23. Murakami K, McGuire R, Cox RA, Jodoin JM, Bjertnaes LJ, Katahira J, Traber LD, Schmalstieg FC, Hawkins HK, Herndon DN, and Traber DL: Heparin nebulization attenuates acute lung injury in sepsis following smoke inhalation in sheep. Shock. 2002;18:236-241.
24. Darien BJ, Fareed J, Centgraf KS, Hart AP, MacWilliams PS, Clayton MK, Wolf H, and Kruse-Elliott KT: Low molecular weight heparin prevents the pulmonary hemodynamic and pathomorphologic effects of endotoxin in a porcine acute lung injury model. Shock. 1998;9:274-281.
25. Tyrrell DJ, Horne AP, Holme KR, Preuss JM, and Page CP: Heparin in inflammation: potential therapeutic applications beyond anticoagulation. Adv Pharmacol. 1999;46:151-208.
26. Dixon B, Santamaria JD, and Campbell DJ: A phase 1 trial of nebulised heparin in acute lung injury. Crit Care. 2008;12:R64.
27. Mahadoo J, Hiebert LM, Jaques LB, and Wright CJ: Endothelial sequestration of heparin administered by the intrapulmonary route. Artery. 1980;7:438-447.
28. van Till JWO, Levi M, Bresser P, Schultz MJ, Gouma DJ, and Boermeester MA: Early procoagulant shift in the bronchoalveolar compartment of patients with secondary peritonitis. J Infect Dis. 2006;194:1331-1339.