Low-Dose Prostacyclin Restores an Increased Protein Permeability after Trauma in Cat Skeletal Muscle

Abstract

Background: Increased microvascular permeability inducing leakage of plasma from the intravascular to the extravascular space after trauma is a pathophysiologic event of great clinical significance. A substance reducing an increased microvascular permeability, and especially an increased protein permeability, therefore could be of value to maintain normovolemia and to reduce the need for plasma substitution. Prostacyclin is suggested to have permeability-reducing properties as shown for fluid permeability, but its effects on protein permeability, which may be controlled by partly different mechanisms, are unclear. The present study evaluates whether prostacyclin at a low, clinically relevant, nonvasodilating dose can reestablish an increased protein permeability after trauma. Methods: The study was randomized, blinded, and performed on surgically traumatized, autoperfused, and denervated cat calf muscle. Relative changes in the osmotic reflection coefficient for albumin after 1.5 hours of prostacyclin (1 ng/min/kg) (n = 7) or vehicle (n = 7) treatment were used as a measure of altered protein permeability from a state of increased permeability after trauma. Results: We found that the osmotic reflection coefficient for albumin was increased by about 35% in the prostacyclin group compared with the vehicle-treated group (p < 0.001). Conclusion: If applicable to humans, prostacyclin is a potential therapy for reducing plasma leakage in the critically ill trauma patient by restoring permeability from an increased level.