Composition of emboli influences the efficacy of thrombolysis with rt-PA in a rat stroke model

Abstract

Background and purpose: The efficacy of thrombolysis with recombinant tissue plasminogen activator and its dependency upon clot composition was tested in an embolic stroke model. Methods: In 53 rats the carotid territory was embolised with two arterial-like type of clots and one venous-like type of clot. The arterial ones were either fibrin poor (group A) or fibrin rich (group B). Hemispheric cerebral blood flow before and after embolisation was measured by intraarterial 133 Xenon injection method. 15 min after embolisation 18 animals were treated with tissue plasminogen activator 20mg/kg, and 35 animals with saline. Carotid angiography displayed the rate of occlusion of the cerebral arterial supply before and after treatment. Brains were fixed after 2 days, evaluated neuropathologically and infarct volume measured. Results: Cerebral blood flow was reduced by 36 to 62% after embolisation. The comparison of post-treatment angiography of treated animals to controls in group embolised with arterial-like fibrin rich clots showed significant (p=0.0163) reperfusion in thrombolytic treated animals. Thrombolytic therapy significantly reduced the infarct volume from 11.6 to 1.9% of embolised hemisphere volume (p=0.019) in group embolised with fibrin-poor clots and from 18.3 to 0.0% (p=0.0001) in the group embolised with fibrin-rich clots. Among the treated animals embolised with fibrin rich clots, both the completely recanalised animals (p=0.0003) and the partially recanalised animals (p=0.027) developed smaller infarctions than control animals. No hemorrhagic complications were observed. The control animals embolised with venous-like clots recanalised spontaneously and developed almost no infarctions and only temporary clinical damage. Conclusions: Early thrombolytic therapy induced recanalisation and reduced infarct volume after embolic stroke, this effect was particularly apparent in the group embolised with fibrin-rich clots.