Resolution rates of artificially produced protein and amino acid oedemas and the effects of a benzopyrone.

The benzopyrone, coumarin, increases the proteolysis of accumulated abnormal protein. It also significantly reduces high-protein oedemas. The main purpose of this study was to link these effects of the drug directly by showing that the products of proteolysis, such as amino acids, are removed from the site of oedema more rapidly than the proteins themselves. Local oedema was produced in the hind limbs of rats by injecting various substances: plasma, the equivalent concentration of amino acids and polyvinylpyrrolidone (PVP), and physiological saline. The rates at which these oedemas were resolved were calculated and compared. The resolution of high-protein oedema (plasma) was biphasic. The first phase was more rapid and probably dependent on maximal lymphatic function. The second phase was slower and continued until the tissues returned to normal. It was probably dependent on proteolysis and began when the more central lymphatic collectors became filled, causing local lymph flow to be progressively reduced. The oedema caused by the injection of amino acids was resolved more rapidly than that caused by plasma, showing that the products of proteolysis are removed from the site of oedema more rapidly than the proteins themselves. The non-metabolizable PVP was not removed more slowly than the plasma but at the same rate as the amino acids, indicating that it was not a suitable control molecule for plasma proteins. The physiological saline was removed more rapidly than all the other injectants. The effect of coumarin on the resolution of these oedemas was investigated. It had no effect in the non-protein oedemas nor in the first 4 h after plasma injection. It did increase the rate of resolution in the second (or proteolysis) phase of plasma removal. This further confirms that coumarin enhances proteolysis and reduces high-protein oedema. It has therefore been shown that coumarin reduces high-protein oedema by splitting the proteins into fragments which are removed from the site of oedema more rapidly than the proteins.