INTRAVENOUS ASPIRIN CAUSES A PARADOXICAL ATTENUATION OF CEREBROVASCULAR THROMBOLYSIS

Background and Purpose Aspirin treatment is recognized as an advantage ous adjunct to thrombolytic agents in myocardial infarct patients. In this study we examined the effects of aspirin on the rate of clot lysi s and on the frequency and extent of hemorrhagic transformations in ra bbit models of embolic stroke. Methods Rabbit models of ex vivo platel et aggregation and cutaneous template bleeding times were used to show the anticoagulant effects of aspirin in our experimental paradigm. We monitored tissue-type plasminogen activator (TPA)-induced clot lysis in two rabbit models of embolic stroke by (1) scintigraphically follow ing the dissolution of a Tc-99m-tagged clot or (2) using roentgenograp hy to follow the disappearance of an Sn-tagged clot. Results In animal s pretreated (18 hours) with a single administration of aspirin (1, 5, or 20 mg/kg IV) or 1 mg/kg per day for 3 days, the aggregation respon se of platelets to collagen (3.3 mu g/mL) or arachidonic acid (0.5 mmo l/L) was attenuated. High-dose aspirin also increased ear template ble eding time from 1.6 to 2.6 minutes. When aspirin (20 mg/kg) was admini stered 18 hours before embolism and subsequent lysis with TPA (0.3 mg/ kg bolus; 3 mg/kg per hour IV), the pretreatment significantly antagon ized the rate and extent of TPA-induced clot lysis by up to 70%. This was confirmed in a second embolic stroke model. The suppression of TPA -induced lysis was reversed by administration of the prostacyclin anal ogue iloprost (10 mu g/kg per hour) directly into the cerebral circula tion. Conclusions We conclude that aspirin reduces the effects of TPA in embolic stroke models. This effect may be the result of a loss of e ndothelial prostacyclin production since the effect is reversed by ilo prost.