Effects of thrombin inhibition with melagatran on renal hemodynamics and function and liver integrity during early endotoxemia

American Journal of Physiology - Regulatory Integrative and Comparative Physiology

Volumn 292, Issue 3, 2007, Pages

  Nitescu, Nicoletta ^a,d   Grimberg, Elisabeth ^a   Ricksten, Sven Erik ^a   Marcussen, Niels ^c   Nordlinder, Hans ^b   Guron, Gregor ^a  

^a UNIVERSITY OF GOTHENBURG   (Sweden)

^b UNIVERSITY OF GOTHENBURG   (Sweden)

^c UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^d SAHLGRENSKA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

Acute kidney failure; Acute liver failure; Coagulation; Multiple organ failure; Sepsis

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; BILIRUBIN; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERCELLULAR ADHESION MOLECULE 1; LIPOPOLYSACCHARIDE; MELAGATRAN; THROMBIN; TUMOR NECROSIS FACTOR ALPHA;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD GAS; CONTINUOUS INFUSION; CONTROLLED STUDY; DRUG BLOOD LEVEL; ENDOTOXEMIA; GENE EXPRESSION; GLOMERULUS FILTRATION; KIDNEY BLOOD FLOW; KIDNEY FUNCTION; LASER DOPPLER FLOWMETRY; LIVER FUNCTION; LIVER HISTOLOGY; LIVER INJURY; MALE; MEAN ARTERIAL PRESSURE; NONHUMAN; PRIORITY JOURNAL; RAT; TUBULAR DYSFUNCTION;

ANIMALS; ANTICOAGULANTS; AZETIDINES; BENZYLAMINES; ENDOTOXEMIA; KIDNEY; LIPOPOLYSACCHARIDES; LIVER; MALE; RATS; RATS, SPRAGUE-DAWLEY; RENAL CIRCULATION; THROMBIN;

EID: 33847766203     PISSN: 03636119     EISSN: 15221490     Source Type: Journal    
DOI: 10.1152/ajpregu.00471.2006     Document Type: Article

References (40)

1. Belge KU, Dayyani F, Horelt A, Siedlar M, Frankenberger M, Frankenberger B, Espevik T, Ziegler-Heitbrock L. The proinflammatory CD14+CD16+DR++ monocytes are a major source of TNF. J Immunol 168: 3536-3542, 2002.
2. Brezis M, Rosen S. Hypoxia of the renal medulla - its implications for disease. N Engl J Med 332: 647-655, 1995.
3. Copple BL, Moulin F, Hanumegowda UM, Ganey PE, Roth RA. Thrombin and protease-activated receptor-1 agonists promote lipopolysaccharide-induced hepatocellular injury in perfused livers. J Pharmacol Exp Ther 305: 417-425, 2003.
4. Coughlin SR. Thrombin signalling and protease-activated receptors. Nature 407: 258-264, 2000.
5. Derkach DN, Ihara E, Hirano K, Nishimura J, Takahashi S, Kanaide H. Thrombin causes endothelium-dependent biphasic regulation of vascular tone in the porcine renal interlobar artery. Br J Pharmacol 131: 1635-1642, 2000.
6. Ding Y, Young CN, Li J, Luan X, McAllister JP 2nd, Clark JD, Diaz FG. Reduced inflammatory mediator expression by pre-reperfusion infusion into ischemic territory in rats: a real-time polymerase chain reaction analysis. Neurosci Lett 353: 173-176, 2003.
7. Elg M, Gustafsson D. A combination of a thrombin inhibitor and dexamethasone prevents the development of experimental disseminated intravascular coagulation in rats. Thromb Res 117: 429-437, 2006.
8. Elg M, Gustafsson D, Deinum J. The importance of enzyme inhibition kinetics for the effect of thrombin inhibitors in a rat model of arterial thrombosis. Thromb Haemost 78: 1286-1292, 1997.
9. Eriksson M, Larsson A, Saldeen T, Mattsson C. Melagatran, a low molecular weight thrombin inhibitor, counteracts endotoxin-induced haemodynamic and renal dysfunctions in the pig. Thromb Haemost 80: 1022-1026, 1998.
10. Eriksson M, Saldeen T, Mattsson C, Larsson A. Effects of melagatran, an inhibitor of thrombin, on fibrin deposits, haemodynamics, and platelet count in endotoxaemic pigs. Acta Anaesthesiol Scand 44: 24-31, 2000.
11. Gui Y, Loutzenhiser R, Hollenberg MD. Bidirectional regulation of renal hemodynamics by activation of PAR1 and PAR2 in isolated perfused rat kidney. Am J Physiol Renal Physiol 285: F95-F104, 2003.
12. Guron G, Marcussen N, Nilsson A, Sundelin B, Friberg P. Postnatal time frame for renal vulnerability to enalapril in rats. J Am Soc Nephrol 10: 1550-1560, 1999.
13. Gustafsson D, Antonsson T, Bylund R, Eriksson U, Gyzander E, Nilsson I, Elg M, Mattsson C, Deinum J, Pehrsson S, Karlsson O, Nilsson A, Sorensen H. Effects of melagatran, a new low-molecular-weight thrombin inhibitor, on thrombin and fibrinolytic enzymes. Thromb Haemost 79: 110-118, 1998.
14. Hagg U, Johansson ME, Gronros J, Naylor AS, Jonsdottir IH, Bergstrom G, Svensson PA, Gan LM. Gene expression profile and aortic vessel distensibility in voluntarily exercised spontaneously hypertensive rats: potential role of heat shock proteins. Physiol Genomics 22: 319-326, 2005.
15. Hatherill M, Tibby SM, Turner C, Ratnavel N, Murdoch IA. Procalcitonin and cytokine levels: relationship to organ failure and mortality in pediatric septic shock. Crit Care Med 28: 2591-2594, 2000.
16. Hewett JA, Jean PA, Kunkel SL, Roth RA. Relationship between tumor necrosis factor-α and neutrophils in endotoxin-induced liver injury. Am J Physiol Gastrointest Liver Physiol 265: G1011-G1015, 1993.
17. Hochart H, Jenkins PV, Smith OP, White B. Low-molecular weight and unfractionated heparins induce a downregulation of inflammation: decreased levels of proinflammatory cytokines and nuclear factor-kappaB in LPS-stimulated human monocytes. Br J Haematol 133: 62-67, 2006.
18. Hoffman M, Cooper ST. Thrombin enhances monocyte secretion of tumor necrosis factor and interleukin-1 beta by two distinct mechanisms. Blood Cells Mol Dis 21: 156-167, 1995.
19. Hoffmann JN, Vollmar B, Inthorn D, Schildberg FW, Menger MD. Antithrombin reduces leukocyte adhesion during chronic endotoxemia by modulation of the cyclooxygenase pathway. Am J Physiol Cell Physiol 279: C98-C107, 2000.
20. Hoffmann JN, Vollmar B, Inthorn D, Schildberg FW, Menger MD. The thrombin antagonist hirudin fails to inhibit endotoxin-induced leukocyte/endothelial cell interaction and microvascular perfusion failure. Shock 14: 528-534, 2000.
21. Iba T, Kidokoro A, Fukunaga M, Nagakari K, Suda M, Yoshikawa S, Ida Y. Antithrombin ameliorates endotoxin-induced organ dysfunction more efficiently when combined with danaparoid sodium than with unfractionated heparin. Intensive Care Med 31: 1101-1108, 2005.
22. Knotek M, Rogachev B, Wang W, Ecder T, Melnikov V, Gengaro PE, Esson M, Edelstein CL, Dinarello CA, Schrier RW. Endotoxemic renal failure in mice: role of tumor necrosis factor independent of inducible nitric oxide synthase. Kidney Int 59: 2243-2249, 2001.
23. Kuzume M, Nakano H, Yamaguchi M, Matsumiya A, Shimokohbe G, Kitamura N, Nagasaki H, Kumada K. A monoclonal antibody against ICAM-1 suppresses hepatic ischemia-reperfusion injury in rats. Eur Surg Res 29: 93-100, 1997.
24. Larsson M, Logren U, Ahnoff M, Lindmark B, Abrahamsson P, Svennberg H, Persson BA. Determination of melagatran, a novel, direct thrombin inhibitor, in human plasma and urine by liquid chromatographymass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 766: 47-55, 2002.
25. McDonald MC, Dhadly P, Cockerill GW, Cuzzocrea S, Mota-Filipe H, Hinds CJ, Miller NE, Thiemermann C. Reconstituted high-density lipoprotein attenuates organ injury and adhesion molecule expression in a rodent model of endotoxic shock. Shock 20: 551-557, 2003.
26. Moulin F, Copple BL, Ganey PE, Roth RA. Hepatic and extrahepatic factors critical for liver injury during lipopolysaccharide exposure. Am J Physiol Gastrointest Liver Physiol 281: G1423-G1431, 2001.
27. Nitescu N, Grimberg E, Ricksten SE, Guron G. Effects of N-acetyl-L-cysteine on renal haemodynamics and function in early ischaemia-reperfusion injury in rats. Clin Exp Pharmacol Physiol 33: 53-57, 2006.
28. Nylander S, Mattsson C. Thrombin-induced platelet activation and its inhibition by anticoagulants with different modes of action. Blood Coagul Fibrinolysis 14: 159-167, 2003.
29. Pallone TL, Zhang Z, Rhinehart K. Physiology of the renal medullary microcirculation. Am J Physiol Renal Physiol 284: F253-F266, 2003.
30. Pawlinski R, Mackman N. Tissue factor, coagulation proteases, and protease-activated receptors in endotoxemia and sepsis. Crit Care Med 32: S293-297, 2004.
31. Pawlinski R, Pedersen B, Schabbauer G, Tencati M, Holscher T, Boisvert W, Andrade-Gordon P, Frank RD, Mackman N. Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia. Blood 103: 1342-1347, 2004.
32. Schiffer ER, Reber G, De Moerloose P, Morel DR. Evaluation of unfractionated heparin and recombinant hirudin on survival in a sustained ovine endotoxin shock model. Crit Care Med 30: 2689-2699, 2002.
33. Schrier RW, Wang W. Acute renal failure and sepsis. N Engl J Med 351: 159-169, 2004.
34. Smits GJ, Roman RJ, Lombard JH. Evaluation of laser-Doppler flowmetry as a measure of tissue blood flow. J Appl Physiol 61: 666-672, 1986.
35. Steinbrenner H, Nguyen TB, Wohlrab U, Scherbaum WA, Seissler J. Effect of proinflammatory cytokines on gene expression of the diabetes-associated autoantigen IA-2 in INS-1 cells. Endocrinology 143: 3839-3845, 2002.
36. Tognetto M, D'Andrea MR, Trevisani M, Guerrini R, Salvadori S, Spisani L, Daniele C, Andrade-Gordon P, Geppetti P, Harrison S. Proteinase-activated receptor-1 (PAR-1) activation contracts the isolated human renal artery in vitro. Br J Pharmacol 139: 21-27, 2003.
37. Vallet B, Wiel E. Endothelial cell dysfunction and coagulation. Crit Care Med 29: S36-S41, 2001.
38. Van Lambalgen AA, van Kraats AA, Mulder MF, Teerlink T, van den Bos GC. High-energy phosphates in heart, liver, kidney, and skeletal muscle of endotoxemic rats. Am J Physiol Heart Circ Physiol 266: H1581-H1587, 1994.
39. Woodman RC, Teoh D, Payne D, Kubes P. Thrombin and leukocyte recruitment in endotoxemia. Am J Physiol Heart Circ Physiol 279: H1338-H1345, 2000.
40. Zeerleder S, Hack CE, Wuillemin WA. Disseminated intravascular coagulation in sepsis. Chest 128: 2864-2875, 2005.