STUDIES ON THE EFFECT OF HUMAN LYS-PLASMINOGEN IN A RAT MODEL OF GLOBAL CEREBRAL-ISCHEMIA

Human lys-plasminogen and the corresponding formulation buffer were te sted in a rat model of global cerebral ischemia (clamping of both caro tid arteries, withdrawal of 5 ml blood for 30 min). The two main param eters, tested in different experimental set-ups, were 1. brain edema ( water content) 23.5 h after reperfusion and 2, assessment of neurologi cal deficits 24, 48 and 72 h after reperfusion. In some groups of anim als of the first set-up, brains were examined histologically for micro vascular fibrin deposits. In a separate group of animals the fibrinoly tic plasma activity of rats treated with 500 CU/kg lys-plasminogen was studied. Concerning brain water content lys-plasminogen completely an tagonized the formation of brain edema when given with 500 caseolytic Units (CU)/kg i.v. with blood reperfusion and was still effective when given 30 min later. 200 CU/kg i.v. given with blood reperfusion as we ll as 500 CU/kg i.v. given 60 min after blood reperfusion proved ineff ective. In none of the brains investigated microvascular fibrin deposi ts were found. In experiments with assessment of neurological deficits , animals treated with 500 CU/kg lys-plasminogen i.v. showed almost no disabilities (like sham operated animals) when compared to ischemic ( positive) controls which were rather severly handicapped. The formulat ion buffer of lys-plasminogen, tested in an equivalent volume, was wit hout any effect in both set-ups. No fibrinolytic activity was found in plasma samples of rats up to 240 min after treatment with 500 CU/kg l ys-plasminogen i.v. It is concluded from these experiments that human lys-plasmin rats against the sequelae of global cerebral ischemia whic h is not related to the well-known fibrinolytic potential but might be a separate quality.