Role of TNF-alpha in local surgical trauma-induced microvascular dysfunction.
OBJECTIVE
The aim of this study was to gain insight into the mechanisms of microvascular dysfunction after local surgical trauma.


METHODS
The effect of anti-tumor necrosis factor (TNF)-alpha antibody (Ab) on microvascular function, including arteriolar diameter response, nutritive perfusion, leukocyte-endothelial cell interaction and endothelial integrity disruption, was studied in hamster skinfold chamber preparations using intravital fluorescence microscopy.


RESULTS
Directly after the surgical procedure, arteriolar diameters were found to be markedly (p < 0.05) reduced, but recovered significantly at 8 h and reached plateau levels after 24 h. Surgical trauma further induced a strong inflammatory response characterized by a significant (p < 0.05) increase in leukocyte adherence to the endothelium of postcapillary venules. This inflammatory response was associated with an increase in microvascular permeability, indicating endothelial integrity disruption. Anti-TNF-alpha Ab had no significant effect on the surgical trauma-induced arteriolar vasomotor dysfunction; however, it effectively (p < 0.05) reduced venular leukocyte adherence and attenuated the increase in microvascular permeability.


CONCLUSIONS
Our study indicates that arteriolar constriction, leukocyte-endothelial cell interaction and endothelial macromolecular leakage have to be considered as the characteristic microvascular response after local surgical trauma. It is conceivable that TNF-alpha plays a role in mediating the inflammatory response, but not the dysfunction of vasomotor control.
Yamauchi
J I
JI
Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany. exjyam@med-rz.uni-sb.de
Vollmar
B
B
Wolf
B
B
Menger
M D
MD
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002199:Capillary Permeability; D002448:Cell Adhesion; D006224:Cricetinae; D007962:Leukocytes / Q000502:physiology; D008647:Mesocricetus; D008833:Microcirculation / Q000502:physiology*; D008856:Microscopy, Fluorescence; D013514:Surgical Procedures, Operative; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*
D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha