DIFFERENTIAL EFFECT OF RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR-INDUCED THROMBOLYSIS IN THE CENTRAL-NERVOUS-SYSTEM AND SYSTEMIC ARTERIES

Recombinant tissue plasminogen activator (rTPA) has been more effective in inducing thrombolysis in laboratory studies of intracranial thrombosis than clinical studies of systemic or coronary thrombosis would indicate. To evaluate this discrepancy, 21 rabbits were subjected to embolic occlusion of the right internal carotid artery (ICA) by retrograde injection of a tin-tagged, 2-hour-old autologous clot through the external carotid artery with angiographic monitoring in the same manner as in a previously reported model. The emboli lodged intracranially at the bifurcation of the ICA in 10 animals and in the cervical ICA in 11 animals. Digital subtraction angiography confirmed total occlusion of the ICA in all animals. Treatment started one-half hour after embolization and consisted of a bolus of 0.5 mg/kg of rTPA followed by an infusion of 1 mg/kg/h for 2 hours. All of the animals with intracranial emboli and 6 of the animals with cervical emboli were treated intravenously. The remaining 5 animals with cervical emboli were treated by intracarotid infusion of the same dose of rTPA. In the intravenously treated group, serial digital subtraction angiography documented thrombolysis in 9 of the 10 animals with intracranial emboli and only 1 of the 6 with cervical emboli. Thrombolysis occurred in 4 of the 5 rabbits with cervical emboli treated with intracarotid rTPA. Intravenous rTPA therapy produced a significantly (P < 0.01) higher rate of thrombolysis in intracranial as compared to cervical thrombus. These results suggest that intravenous rTPA may be more effective in the treatment of thromboembolic occlusion of intracranial arteries than of systemic arteries, and that intra-arterial rTPA therapy may be indicated for treatment of acute systemic arterial occlusions. Anatomical and physiological differences between the cervical and the intracranial segments of the carotid artery may affect the response to rTPA-induced thrombolysis.