Vascular effects of prostacyclin in cat skeletal muscle and in the traumatised rat brain

Sammanfattning: Disturbances in microvascular function may be important for tissue damage in many disease states. Prostacyclin, a substance produced by endothelial cells, is important for the maintenance of normal vascular homeostasis and is a potential drug for treatment of microvascular dysfunction, but indications and optimal dosage remains to be established. In the present thesis we evaluated the capillary filtration coefficient (CFC)-method as a tool to investigate changes in microvascular permeability in vivo. In contrast to previous studies we found that CFC is not significantly influenced by alterations in precapillary sphincter activity and concluded that changes in CFC reflect changes in fluid permeability in cat skeletal muscle. Using the CFC-method we investigated effects of prostacyclin on microvascular fluid permeability and found that prostacyclin may decrease fluid permeability through opening of ATP-dependent potassium channels. We also found that prostacyclin may be released and decrease fluid permeability following increases in plasma concentrations of endothelin-1. We also investigated effects of prostacyclin in a low dose, which is clinically applicable without side effects such as hypotension, on macromolecular permeability in cat skeletal muscle and found that such a treatment could counteract an increase in macromolecular permeability. In order to evaluate potentially beneficial effects on microvascular perfusion following a brain trauma, prostacyclin in a low dose was administered following traumatic brain injury in rats. Prostacyclin reduced cell death simultaneously with an increase in cerebral blood flow and an increase in the number of perfused capillaries in the injured part of the brain. The results presented in the present thesis suggest that treatment with prostacyclin in low doses may be beneficial in disease states characterised by an impaired microvascular perfusion and increased vascular permeability such as following a brain trauma.