Action of Gold Sodium Thiomalate on Experimental Thrombosis In Vivo

In order to study the effect of gold compounds on the action of thrombin in vivo, experiments were performed to measure platelet survival and the weight of thrombus formation in experimental models of intra-aortic thrombosis by two indwelling aortic catheter methods. We have called these the long and short catheter methods. Platelet survival was reduced in all gold-treated and control animals which had indwelling aortic catheters. In the long catheter model, New Zealand White male rabbits were treated with one of the following: gold sodium thiomalate, sterile water, gold thioglucose, gold sodium thiosulfate, disodium thiomalate. Gold sodium thiomalate-treated rabbits had a reduced weight of experimentally induced intra-aortic thrombi compared with animals treated with sterile water or equimolar concentrations of gold thioglucose, gold sodium thiosulfate, or disodium thiomalate. This reduction in thrombus weight in the animals treated with gold sodium thiomalate was not reflected by changes in platelet survival or fibrinolysis. The serum gold levels achieved in these in vivo experiments was in the range of 5.0 × 10-5 to 1.0 × 10-4 M. These values are comparable to levels which can be achieved in human subjects immediately after a gold injection. In the short catheter model, New Zealand White male rabbits were treated with either gold sodium thiomalate, gold thioglucose, disodium thiomalate, or auranofin. Controls were given either water or 0.05% chlorocresol. Water-treated and gold sodium thiomalate-treated animals were also given 51Cr-labeled platelets and 125I-fibrinogen before insertion of the catheter. Gold sodium thiomalate-treated animals had a significant reduction in mean thrombus weight compared with those treated with water, gold thioglucose, disodium thiomalate, auranofin, or chlorocresol. Gold sodium thiomalate-treated animals had a reduced amount of 125I-fibrin accumulation on the vessel wall and thrombus compared with the water-treated group, but no significant reduction in 51Cr-labeled platelet accumulation. The results indicate that pretreatment with gold sodium thiomalate reduces the weight of thrombus in this experimental model of continuous vessel wall injury. The reduction in thrombus weight recorded in these studies was not related to any effect of fibrinolysis or platelet survival.