Plasminogen Plus rt-PA Improves Intraarterial Thrombolytic Therapy in Acute Ischemic Stroke

In the past 2 years we have undertaken further efforts to improve the technique of local intraarterial fibrinolysis (LIF), before beginning a multicenter study. The effectiveness of fibrinolysis from the technical point of view is defined as the clot volume being lysed per time. Early studies demonstrated that local urokinase (u-PA) treatment is a safe and effective treatment [1], but obviously not the optimal one [2–4]. This was more clearly seen after the indication for treatment was expanded from basilar to carotid territory strokes: recanalization of middle cerebral artery (MCA) occlusion occurred almost regularly, but it often was incomplete depending on the different sites of occlusion [5]. From the clinical point of view, however, the success of fibrinolysis concerning the outcome depends less on recanalization in general than on its completeness. Tissue plasminogen activator (rt-PA) is a more fibrin-specific plasminogen (PG) activator than u-PA and thus thought to be a more effective drug, able to remove a larger clot volume in a shorter period of time with fewer side effects. After a clinical pilot study [4] had shown, however, that rt-PA used in a seemingly comparable dose was not superior to u-PA, we developed the following hypothesis: a. To improve the effectiveness of LIF, it is not reasonable to increase the local dose of u-PA or rt-PA in view of side effects that might be expected. b. The proteolytic enzyme that is responsible for fibrinolysis is plasmin. Because all the fibrinolytic drugs are activators converting PG into plasmin, fibrinolysis might be improved to a lesser degree by increasing the dose of activators, but far more by adding its substrate: plasminogen.