gms | German Medical Science

Joint German Congress of Orthopaedics and Trauma Surgery

02. - 06.10.2006, Berlin

Selective inhibition of COX-2 restores trauma-induced microcirculatory dysfunctions by abrogation of inflammation

Meeting Abstract

  • M. Amon - Institute for Clinical & Experimental Surgery, University of Saarland, Homburg/Saar, Germany
  • J. Philippe - Institute for Clinical & Experimental Surgery, University of Saarland, Homburg/Saar, Germany
  • C. Meier - Division of Trauma Surgery, University Hospital Zurich, Zurich, Switzerland
  • Y. Harder - Division of Plastic & Reconstructive Surgery, University Hospital Geneva, Geneva, Switzerland
  • M.D. Menger - Institute for Clinical & Experimental Surgery, University of Saarland, Homburg/Saar, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie. 70. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 92. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie und 47. Tagung des Berufsverbandes der Fachärzte für Orthopädie. Berlin, 02.-06.10.2006. Düsseldorf, Köln: German Medical Science; 2006. DocE.7.4-1252

The electronic version of this article is the complete one and can be found online at:

Published: September 28, 2006

© 2006 Amon et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Introduction: Irreversible microcirculatory dysfunction and inflammation are leading causes for inadequate wound healing and infections after trauma. Inhibition of cyclooxygenase-2 may prevent this deleterious outcome. The aim of our study was to analyze the effect of NS-398, a selective COX-2 inhibitor, on microcirculatory and inflammatory dysfunctions in a chronical animal model of direct soft tissue trauma.

Methods: Soft tissue trauma was induced in dorsal skinfold chambers of C57Bl/6 mice by a weight drop device (25g; 14.5cm). Arteriolar diameters, blood flow and functional capillary density were analyzed and the inflammatory response was assessed by counting the number of venular adherent leukocytes before trauma and after 1h, 24h, 3d and 5d. Animals were randomly allocated to one of three experimental groups: (1) trauma without treatment (n=6); (2) trauma with NS-398 (0.5mg/kg bw; 30min before trauma; n=6); (3) skinfold chambers without trauma and treatment (control; n=6).

Results: In controls, both microcirculatory and inflammatory parameters did not significantly change, while trauma induced an early inflammatory response, indicated by an increase of leukocyte adherence (238±37/cm2; 8h). This was associated by irreversible arteriolar constriction (71±3% of baseline; 5d), reduced blood flow (48±4%) and nutritive capillary perfusion failure (65±3%). COX-2-inhibition almost completely abrogated leukocytic inflammation (105±12/cm2) during the early post-traumatic period. This was associated with restoration of perfusion at the later time points (i.e. 3d and 5d). Both arteriolar diameter (102±2% of baseline; 5d) and blood flow (106±5%) could be restored to control values (p<0.05 versus trauma). Nutritive perfusion did not completely recover to baseline, however, functional capillary density was significantly improved (p<0.05) by COX-2-inhibition (84±3%) compared to non-treated trauma controls.

Conclusion: Selective inhibition of cyclooxygenase-2 attenuates the early leukocytic response upon trauma and restores delayed microcirculatory dysfunctions. These results indicate that (i) delayed microcirculatory dysfunctions are triggered by the early leukocytic response and (ii) the anti-inflammatory therapy with COX-2-inhibitors may prevent late complications of soft tissue trauma which are caused by nutritive perfusion failure-induced tissue ischemia.