Thrombolytic treatment of clot embolism in rat - Comparison of intra-arterial and intravenous application of recombinant tissue plasminogen activator

Copyright 2002 American Heart Association, Inc.Background and Purpose-We sought to test the hypothesis that intra-arterial recombinant tissue plasminogen activator (rtPA) treatment of thromboembolic stroke is more efficient than intravenous application. Methods-Rats were embolized by intracarotid injection of autologous fibrin-rich blood clots. One hour later rtPA (10 mg/kg) was infused either intravenously (n=8) or intra-arterially (n=8). Control rats (n=8) received intra-arterial infusion of saline. Treatment was monitored by MR perfusion-weighted imaging and apparent diffusion coefficient (ADC) imaging, and outcome was evaluated by comparing incidence of hemorrhages and lesion volumes of ATP and pH. Results-Clot embolism led to a decline of perfusion- weighted imaging signal intensity in the middle cerebral artery territory to <40% of control. Both intra-arterial and intravenous treatment significantly improved blood flow in cerebral cortex but not in caudate putamen. In untreated animals, ATP and pH lesion volumes were 510.3+/-94.5 and 438.6+/-39.2 mm(3) at 7 hours after clot embolism, respectively. Both intravenous and intra-arterial rtPA treatment produced hemorrhagic complications but reduced ATP lesion size to 296.2+/-136.1 and 370.3+/-103.7 mm(3) and reduced pH lesion size to 263.3+/-114.6 and 303.3+/-103.0 mm(3), respectively (P