COMPARISON OF INTRATHECALLY ADMINISTERED UROKINASE, TISSUE-TYPE PLASMINOGEN-ACTIVATOR, AND COMBINATION OF UROKINASE AND LYSINE-PLASMINOGEN FOR CLOT LYSIS AFTER EXPERIMENTAL SUBARACHNOID HEMORRHAGE IN DOGS

OBJECTIVE: The purpose of this study was to compare the fibrinolytic e ffect of urokinase (UK) with that of tissue plasminogen activator (tPA ) on subarachnoid clots and to investigate the effect of lysine-plasmi nogen (Lys-plg) on fibrinolytic therapy. METHODS: We measured subarach noid clot lysis rate chronologically for 24 hours during continuous in trathecal irrigation with tPA or UK alone in a canine subarachnoid hem orrhage model. Also, we measured the clot lysis rate for 24 hours duri ng continuous irrigation with UK and Lys-plg or with UK after preadmin istration of Lys-plg in the same model. RESULTS: The rate of clot lysi s caused by UK and tPA dose-dependently increased up to 3,000 IU/ml an d 125,000 IU/ml, respectively. With the same molar concentrations, the lytic effect of tPA was significantly higher than that of UK. The slo pe of the dose-response curve, however, was almost the same with both agents, and the slope of the dose-response curve of UK and tPA for a 2 4-hour irrigation was 25 and 23% per log 10 concentration, respectivel y. On the other hand, clot lysis with the combined use of UK and Lys-p lg was higher than that with the single use of UK. Particularly, the p readministration of Lys-plg markedly enhanced clot lysis by UK at the early stage of irrigation. CONCLUSION: Subarachnoid clot lysis can be accelerated by administration of Lys-plg before UK administration and by use of high concentrations of UK or tPA.