Prostacyclin counteracts the increase in capillary permeability induced by tumour necrosis factor-α
To analyse how prostacyclin interferes with the short-term local circulatory effects of tumour necrosis factor-α (TNFα) in a skeletal muscle.
An autoperfused sympathectomised cat gastrocnemius muscle enclosed in a plethysmograph.
Arterial blood flow, total and segmental vascular resistances (large-bore arterial vessels, arterioles and veins), hydrostatic capillary pressure, tissue volume and capillary filtration coefficient were followed during local intraarterial infusion of TNFα at various rates (2.5, 5.0 and 7.5 μg/kg per min) and during intra-arterial infusion of prostacyclin simultaneously with the highest dose of TNFα. The capillary filtration coefficient reflects the capillary surface for fluid exchange.
Arterial infusion of TNFα had no influence on vascular resistance up to 5.0 μg/kg per min but induced vasodilation at 7.5 μg/kg per min. No effects on the recorded hydrostatic capillary pressure were observed. The capillary filtration coefficient and the capillary filtration increased with the infusion rate of TNFα the former by 55%. Simultaneous arterial infusion of prostacyclin (350 ng/kg per min) caused further vasodilation and an increase in hydrostatic capillary pressure and completely restored the capillary filtration coefficient to control. The TNFα-induced filtration was partly restored.
The local circulatory effect of TNFα is small apart from a graded increase in the capillary filtration coefficient, most likely reflecting an increase in capillary permeability. The prostacyclininduced decrease in capillary filtration coefficient most likely reflects a restoration of capillary permeability. The TNFα-induced transcapillary filtration is not fully reduced by prostacyclin due to a simultaneous increase in hydrostatic capillary pressure.
Key wordsCapillary permeability Capillary pressure Critical illness Haemodynamics Prostacyclin Sepsis Tumour necrosis factor Vascular resistance
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