Volume 4 Supplement 1

20th International Symposium on Intensive Care and Emergency Medicine

Open Access

Endotoxin-induced capillary perfusion failure and leukocyte adhesion is not prevented by the thrombin inhibitor hirudin: an intravital microscopic study

  • JN Hoffmann1,
  • B Vollmar2,
  • D Inthorn1,
  • FW Schildberg1 and
  • MD Menger2
Critical Care20004(Suppl 1):P32


Published: 21 March 2000

Full text

Besides its central role in coagulatory pathways, thrombin is thought to be a key mediator of macrophage and granulocyte activation. During recent years the concept of coagulatory inhibition by the specific thrombin inhibitor hirudin has been established to treat septic disorders. Since basic mechanisms of sepsis include leukocyte-endothelial cell interaction as well as deterioration of capillary perfusion, we hypothesised that hirudin would modulate leukocyte activation and microvascular injury. In a skinfold preparation of Syrian hamsters, severe endotoxemia was induced by intravenous administration of endotoxin (LPS,E. coli, 2 mg/kg). Hirudin (0.25 mg/kg) was substituted intravenously during 4 h after the induction of endotoxemia [n=7, hirudin group (hirudin)]. In control animals [n=6, Control group (control)], LPS was given without hirudin substitution. By intravital fluorescence microscopy leukocyte-endothelial cell interaction and functional capillary density (FCD, a measure of capillary perfusion) were analysed during a 24 h period after the LPS injection. Hirudin effectively normalised thromboplastin time and antithrombin activity when compared to controls (P<0.05, ANOVA). However, hirudin did not attenuate LPS-induced arteriolar and venular leukocyte adherence during 24 h (P>0.05, MANOVA). In parallel, hirudin caused significant deterioration in FCD over time when compared to controls (hirudin: baseline=171± 19 vs 16± 9 at 24 h; control: baseline =150± 20 vs 62± 18 at 24 h; P<0.05 MANOVA). The decrease of FCD in hirudin animals was associated with a significant increase of wet-to-dry weight ratios in different organs (lung, kidney, muscle, and small intestine; P<0.05 vs control, ANOVA). Thus, our experiment does not indicate a protective effect of hirudin on microcirculation during endotoxemia, despite an improvement of coagulatory parameters. This result may at least in part explain the lack of efficacy of hirudin efficacy on lethality during endotoxemia and sepsis.

Authors’ Affiliations

Department of Surgery Klinikum Groβhadern, Ludwig-Maximilians-University Munich
Department of Clinical and Experimental Surgery, University of Homburg/Saar


© Current Science Ltd 2000