REDUCTION OF INFARCT VOLUME AND MORTALITY BY THROMBOLYSIS IN A RAT EMBOLIC STROKE MODEL

Background and Purpose: Thrombolytic therapy with recombinant tissue plasminogen activator was tested in a rat embolic stroke model. Methods: The rat carotid territory was embolized with arterial-like microthrombi formed under pressure. Hemispheric cerebral blood flow before and after embolization was measured by the intra-arterial Xenon-133 injection method. Fifteen minutes after embolization, 24 rats were treated with 3 mg/kg or 10 mg/kg tissue plasminogen activator, and 27 were treated with saline. Carotid angiography displayed the rate of occlusion of the cerebral arterial supply before and after treatment. Brains were fixed and evaluated neuropathologically and infarct volume was measured. Results: Cerebral blood flow was reduced 70-86% after embolization. The comparison of pretreatment and posttreatment angiography showed significant (p=0.0005) reperfusion in the treated rats. Thrombolytic therapy significantly reduced the infarct volume from 55.1% to 24.4% of embolized hemisphere volume (p=0.007) and increased the survival rate from 0.48 to 0.96 (p=0.0004). Fifty-three percent of the embolized rats recanalized completely after thrombolytic treatment and developed almost no infarction (median volume 2.8%), and all survived. No hemorrhagic complications were observed. Conclusions: Early thrombolytic therapy induced recanalization and reduced mortality and infarct volume after embolic stroke in this model.