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

Abstract

We sought to test the hypothesis that intra-arterial recombinant tissue plasminogen activator (rtPA) treatment of thromboembolic stroke is more efficient than intravenous application. 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. 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<0.05 for untreated versus treated rats; no difference between intravenous and intra-arterial treatment). ADC imaging revealed that lesion reduction was due to inhibition of infarct growth but not to reversal of primary injury. This study documents reduction of injury by rtPA treatment but does not reveal a difference between intra-arterial and intravenous application. Our data do not support an advantage of intra-arterial thrombolysis.