In vivo effects of tumor necrosis factor-alpha on capillary permeability and vascular tone in a skeletal muscle

Background. The present study aims at analysing short-term effects of TNF alpha on capillary permeability, on transcapillary fluid fluxes, and on vascular tone in a whole organ cat skeletal muscle e in vivo preparation. Methods. The denervated muscle was isolated from the body but with intact vascular supply. The experimental setup allowed continuous recording of vascular tone, of hydrostatic capillary pressure and tissue volume variations. The capillary filtration coefficient (CFC), which represents the net effect for transcapillary fluid exchange of capillary permeability and number of open capillaries, was calculated before and during intra-arterial TNF infusion. Results. We found that TNF had a minor effect on vascular tone in terms of a small vasodilation, and that no effect on hydrostatic capillary pressure could be recorded. CFC increased by 64% during the TNF infusion and this increase must be attributed to an increase in capillary permeability rather than an increase in the number of capillaries available for fluid exchange since the TNF effect on vascular tone is small. This was also supported by TNF-induced transcapillary filtration. Conclusions. TNF is a potent drug for increasing capillary permeability causing transcapillary filtration in vivo. Its release, e.g. during sepsis, may therefore contribute to the capillary leakage often seen in this clinical situation.