Thorac Cardiovasc Surg 2001; 49(3): 157-161
DOI: 10.1055/s-2001-14293
Original Cardiovascular
Original Paper
© Georg Thieme Verlag Stuttgart · New York

Hirudin Protects from Leukocyte/Endothelial Cell Interaction
Induced by Extracorporeal Circulation[*]

M. Kamler1 , T. Chatterjee2 , A. Stemberger3 , M. M. Gebhard1 , S. Hagl2 , H. Jakob1
  • 1Department of Thoracic and Cardiovascular Surgery, University of Essen, Germany
  • 2Department of Exp. and Cardiac Surgery, University of Heidelberg, Germany
  • 3Department Exp. Surgery, Technical University Muenchen, Germany
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
31. Dezember 2001 (online)

Background: The clinical complications of Extracorporeal Circulation (ECC) have been linked to disturbances in the microcirculation. In order to prevent these deleterious effects, a biodegradeable agent to coat the extracorporeal circuit was tested. Methods: Intravital fluorescence microscopy was used on the hamster skinfold chamber model in permanently instrumented, awake animals. ECC was introduced via a micro-roller-pump and a silicon tube shunted between the carotid artery and the jugular vein. The ECC-tube system was coated with PEG-Hirudin-Iloprost, two additional groups received either Iloprost i. v. (0,8 mg/kg/h) or Hirudin i. v. (1 mg/kg b. w.). Results: ECC for 20 minutes resulted in an increase in rolling and adherent leukocytes in postcapillary venules (Roller 9 to 36 [%]; Sticker 24 to 330 [n/mm2]). Use of the coated tube system reduced L/E cell interaction (Roller 9 to 24* [%], Sticker 28 to 194* [n/mm2]; *p < 0.05), whereas Hirudin i. v. nearly abolished it. Conclusions: The protective effects of the coating and of Hirudin i. v are probably a result of an attenuated activation of the coagulation-fibrinolytic system.

1 *Results were presented in part at the 3rd Joint meeting of the German, the Austrian and the Swiss Societies for Thoracic and Cardiovascular Surgery, February 2000 in Lucerne, CH.

References

  • 1 Butler J, Rocker G M, Westaby S. Inflammatory response to cardiopulmonary bypass.  Ann Thorac Surg. 1993;  55 552-559
  • 2 Gillinov A M, Redmond J M, Winkelstein J A, Zehr K J, Herskowitz A, Baumgartner W A, Cameron D E. Complement and neutrophil activation during cardiopulmonary bypass a study in the complement-deficient dog.  Ann Thorac Surg. 1994;  57 345-352
  • 3 Hall R I, Smith M S, Rocker G. The systemic inflammatory response to cardiopulmonary bypass pathophysiological, therapeutic, and pharmacological considerations.  Anesth Analg. 1997;  85 (4) 766-782
  • 4 Harlan J M. Neutrophil-mediated vascular injury.  Acta Med Scand. 1987;  715 123-129
  • 5 Kamler M, Jakob H, Lehr H A, Gebhard M M, Hagl S. Direct visualization of leukocyte/endothelial cell interaction during extracorporal circulation (ECC) in a new animal model.  Eur J Cardiothorac Surg. 1997;  11 973-980
  • 6 Gabaldon M, Capdevila C, Zuniga A. Effect of spontaneous pathology and thrombin on leukocyte adhesion to rat aortic endothelium.  Atherosclerosis. 1992;  93 (3) 217-228
  • 7 Herrmann R, Schmidmaier G, Markl B, Resch A, Hahnel I, Stemberger A, Alt E. Antithrombogenic coating of stents using a biodegradable drug delivery technology.  Thrombosis and Haemostasis. 1999;  82 (1) 51-57
  • 8 Alt E, Beilharz C, Preter D, Schmidmaier G, Pasquantonio J, Erhard W, Stemberger A, Schömig A. Reduzierung der Restenose durch eine biodegradierbare Stentbeschichtung mit einem Polylactid als Grundsubstanz sowie Hirudin und Prostacyclin als Wirksubstanzen. 63. Jahrestagung der Deutschen Kardiologischen Gesellschaft (DKG) April 1997. 1996
  • 9 Endrich B, Asaishi K, Gotz A, Messmer K. Technical report - a new chamber technique for microvascular studies in unanesthetized hamsters.  Res Exp Med Berl. 1980;  177 125-134
  • 10 Hirthler M, Simoni J, Dickson M. Elevated levels of endotoxin, oxygen-derived free radicals, and cytokines during extracorporeal membrane oxygenation.  J Pediatr Surg. 1992;  27 199-1202
  • 11 Cremer J, Martin M, Redl H, Bahrami S, Abraham C, Graeter T, Haverich A, Schlag G, Borst H G. Systemic inflammatory response syndrome after cardiac operations.  Ann Thorac Surg. 1996;  61 1714-1720
  • 12 Bizios R, Lai L C, Cooper J A, Vecchio P, Del J, Malik A B. Thrombin-induced adherence of neutrophils to cultured endothelial monolayers: increased endothelial adhesiveness.  J Cell Physiol. 1988;  134 (2) 275-280
  • 13 Moser R, Groscurth P, Fehr J. Promotion of transendothelial neutrophil passage by human thrombin.  J Cell Sci. 1990;  96 (4) 737-744
  • 14 Wendel H P, Heller W, Gallimore M J. Influence of heparin, heparin plus aprotinin and hirudin on contact activation in a cardiopulmonary bypass model.  Immunopharmacology. 1996;  32 57-61
  • 15 Lehr H A, Becker M, Marklund S L, Hubner C, Arfors K E, Kohlschutter A, Messmer K. Superoxide-dependent stimulation of leukocyte adhesion by oxidatively modified LDL in vivo.  Arterioscler Thromb. 1992;  12 824-829
  • 16 Agnelli G, Sonaglia F. Clinical status of direct thrombin inhibitors.  Critical reviews in Oncology/Hematology. 1999;  31 97-117
  • 17 Striggow F, Riek M, Breder J, Henrich-Noack P, Reymann K G, Reiser G. The protease thrombin is an endogenous mediator of hippocampal neuroprotection against ischemia at low concentrations but causes degeneration at high concentrations.  Proc Natl Acad Sci USA. 2000;  97 2264-2269
  • 18 Potzsch B, Madlener K, Seelig C, Riess C F, Greinacher A, Muller-Berghaus G. Monitoring of r-hirudin anticoagulation during cardiopulmonary bypass - assessment of the whole blood ecarin clotting time.  Thromb Haemost. 1997 (May);  77 (5) 920-925
  • 19 Longrois D, de Maistre E, Bischof N, Dopff C, Meistelman C, Angioi M, Lecompte T. Recombinant hirudin anticoagulation for aortic valve replacement in heparin-induced thrombocytopenia (In Process Citation).  Can J Anaesth. 2000;  47 255-260
  • 20 Erlansson M, Bergqvist D, Persson N H, Svensjo E. Modification of postischemic increase of leukocyte adhesion and vascular permeability in the hamster by Iloprost.  Prostaglandins. 1991;  41 (2) 157-168
  • 21 Muller B, Schmidtke M, Witt W. Adherence of leucocytes to electrically damaged venules in vivo Effects of iloprost, PGE1, indomethacin, forskolin, BW 755 C, sulotroban, hirudin, and thrombocytopenia.  Eicosanoids. 1988;  1 (1) 13-17

1 *Results were presented in part at the 3rd Joint meeting of the German, the Austrian and the Swiss Societies for Thoracic and Cardiovascular Surgery, February 2000 in Lucerne, CH.

Dr. med. Markus Kamler

Department of Thoracic and Cardiovascular Surgery
University of Essen

Hufelandstraße 55

45122 Essen

Germany

Telefon: +49-201-723-315

Fax: +49-201-723-5931

eMail: markus.kamler@uni-essen.de