An integration of the modes of action of coumarin. An explanation of its effectiveness as a therapy for thermally injured tissue.

The mode of action of coumarin is well suited to the relief of high-protein oedemas. It binds rapidly to the serum albumins, and the protein binding capacity of a substance provides insight into its interaction with sites of biological activity. Together with proteins, inflowing through the damaged capillary endothelium after thermal injury, it is taken up by the monocytes in the inflamed tissues and by the resident macrophages. Coumarin can stimulate these cells to enhanced proteolysis of the engulfed protein which is digested to debris of molecular weight less than 1000. This is on the other hand readily utilisable protein for the large number of monocytes to mature and differentiate into macrophages. Coumarin may dissociate from protein in the tissue and cause local site activation or even activate all cell sites increasing cell numbers or rejuvenate older phagocytic cells and stimulate the reticulo-endothelial system (RES). A passing histamine-like effect of coumarin and other benzopyrones is an indirect stimulant for the RES. The released injurious amines open additional numbers of endothelial intercellular junctions, allowing extra protein and fluid into the interstitial tissues. A reinforced phagocytosis follows and results in more rapid and complete digestion. The action of the drug in causing the opening of intercellular junction is very beneficial. The extra protein is of little consequence, since its inflow is more than compensated for by the other actions of the drug which results in its lysis. Coumarin has also a number of other important actions on the vascular system. It causes constriction of the precapillary sphincters and a dilatation of the arterio-venous anastomosis. The result is an increased blood pressure and flow, and a better oxygen supply of the area. It is able to restore the deformability of the red blood cell to near normal levels and to protect the thrombocyte by membrane stabilizing. The result is a reduced likelihood of thrombosis and embolism. By increasing the glucose uptake and transport the benzopyrones can improve the chance of survival of those cells in stagnant areas of the circulation.