TISSUE PLASMINOGEN-ACTIVATOR REDUCES BRAIN INJURY IN A RABBIT MODEL OF THROMBOEMBOLIC STROKE

Tissue plasminogen activator is an endogenous fibrin-specific serine protease with potent thrombolytic activity. We investigated the efficacy of tissue plasminogen activator in reducing cerebral infarct size after thromboembolic stroke in a rabbit model. Seventeen rabbits were randomized to receive either tissue plasminogen activator (2.5 mg/kg, n = 6) or vehicle control (n = 11). We controlled mean arterial pressure, hematocrit, and arterial blood gases before and after the intracarotid embolization of an autologous clot. Cerebral blood flow (cm3/100 g/min) (mean+/-SEM) was immediately reduced from 55.2+/-7.7 to 8.5+/-2.5 in the control group and from 61.8+/-14.8 to 10.0+/-3.5 in the treated group after embolization. Cerebral blood flow recovered significantly within 60 minutes of thrombolytic therapy and attained a value of 59.6+/-10.0 cm3/100 g/min 4 hours after embolization, whereas cerebral blood flow in control animals demonstrated only a minimal recovery to 15.3+/-8.9 cm3/100 g/min. Cerebral infarct size (percent of hemisphere) was reduced from 34.4+/-5.6% in control animals to 8.8+/-5.6% in treated animals (mean+/-SEM,p < 0.01). These results suggest that tissue plasminogen activator may be efficacious in restoring cerebral blood flow and thus limiting infarct size in acute thromboembolic stroke.