Reduction of infarct volume by thrombolysis with rt-PA in an embolic rat stroke model

Abstract

Thrombolytic therapy with recombinant tissue plasminogen activator was tested in an embolic stroke model.

In rats the internal carotid territory was embolized through the internal carotid artery with 50//1 thrombin-rich (n = 18), 50μ1 thrombin-poor (n = 17) and 20μ1 thrombin poor (n = 13) suspension of arterial-like microthrombi formed under pressure. Hemispheric cerebral blood flow before and after embolization was measured by intra-arterial ¹³³Xe injection method. Fifteen minutes after embolization 19 animals were treated with tissue plasminogen activator 20mgkg⁻¹, and 22 animals with saline. Carotid angiography displayed the degree of occlusion of the cerebral arterial supply before and after treatment. Brains were evaluated neuropathologically and infarct volume measured.

Cerebral blood flow was reduced 72% after embolization with 50 μl emboli suspension and 32% after embolization with 20 μl suspension. The comparison of pre- and post-treatment angiography showed some recanalization in the treated animals, control animals had no recanalization. Thrombolytic therapy reduced the infarct volume from 72.8% to 20.9% of embolized hemisphere volume (p = 0.0037) in the 50-fA thrombin rich-embolized group, from 22.9 to 9.0 (NS) in the 50-μl-thrombin-poor-embolized group and from 6.6 to 0.0 (NS) in the 20-μ1-embolized group. One third of treated animals recanalized completely and developed smaller (p = 0.03) infarcts than the non-recanalized. No hemorrhagic complications were observed.

Early thrombolytic therapy reduced infarct volume after embolic stroke in this model, this effect was dependent upon recanalization.

Key Words:

• thrombolytic therapy
• recombinant tissue plasminogen activator
• acute ischaemic stroke
• cerebral infarction and embolism
• experimental thromboembolism
• in vitro thrombotic clotting
• cerebral blood flow