PROSTACYCLIN COUNTERACTS THE INCREASE IN CAPILLARY-PERMEABILITY INDUCED BY TUMOR-NECROSIS-FACTOR-ALPHA

Objective. To analyse how prostacyclin interferes with the short-term local circulatory effects of tumour necrosis factor-alpha. (TNF alpha) in a skeletal muscle. Design: An autoperfused sympathectomised cat ga strocnemius muscle enclosed in a plethysmograph. Interventions: Arteri al blood flow, total and segmental vascular resistances (large-bore ar terial vessels, arterioles and veins), hydrostatic capillary pressure, tissue volume and capillary filtration coefficient were followed duri ng local intraarterial infusion of TNFalpha at various rates (2.5, 5.0 and 7.5 mu g/kg per min) and during intra-arterial infusion of prosta cyclin simultaneously with the highest dose of TNFalpha. The capillary filtration coefficient reflects the capillary surface for fluid excha nge. Results. Arterial infusion of TNF, had no influence on vascular r esistance up to 5.0 mu g/kg per min but induced vasodilation at 7.5 mu g/kg per min. No effects on the recorded hydrostatic capillary pressu re were observed. The capillary filtration coefficient and the capilla ry filtration increased with the infusion rate of TNFalpha, the former by 55 %. Simultaneous arterial infusion of prostacyclin (350 ng/kg pe r min) caused further vasodilation and an increase in hydrostatic capi llary pressure and completely restored the capillary filtration coeffi cient to control. The TNFalpha-induced filtration was partly restored. Conclusions: The local circulatory effect of TNFalpha is small apart from a graded increase in the capillary filtration coefficient, most l ikely reflecting an increase in capillary permeability. The prostacycl in-induced decrease in capillary filtration coefficient most likely re flects a restoration of capillary permeability. The TNF alpha-induced transcapillary filtration is not fully reduced by prostacyclin due to a simultaneous increase in hydrostatic capillary pressure.