Quantitative assessment of subcutaneous fibrinolysis in the rat

A clot lysis model in the rat was described which was responsive to manipulation of the fibrinolytic system. By employing [125I]-labeled fibrinogen in homologous, plasminogen-deficient plasma, clots were prepared in Teflon-perforated cylinders and were implanted subcutaneously. After a brief lag phase, lysis proceeded essentially linearly with 70% of the clot resolved within 12 days. Enhancement of lysis was achieved with a stimulator of fibrinolysis, stanozolol; and inhibition, with the antifibrinolytic, tranexamic acid. Other drugs affecting blood pressure, inflammation, or connective tissue growth had no effect on lysis. Interstitial fluid collected from empty cylinders and fluid obtained from the recovered clots were monitored for plasminogen, alpha 2-antiplasmin, plasminogen activator, and plasminogen activator inhibitor using sensitive and specific assays. All of these fibrinolytic proteins were quantitated relative to their plasma concentrations. The most striking differences between the two fluids and plasma were a threefold higher concentration of the plasminogen activator inhibitor and only traces of free tissue plasminogen activator in the fluids. Nevertheless, significant tissue plasminogen activator was delivered to the clot. It was concluded that lysis occurred via delivery of the fibrinolytic system in interstitial fluid. It is suggested that this model is a technically simple and quantitative screen in vivo for potentially fibrinolytic or antifibrinolytic agents.