Jornal de Pesquisa e Desenvolvimento
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Efficacy of Low Dose Tenecteplase in Restoring Vessel Patency in a Clinically Relevant Large Animal Experimental Model

Tseliou E, Ntalianis A, Diakos N, Pozios H, Repasos V, Katsaros F, Dimopoulos S, Kontopidi V, Margari Z and Nanas JN

Background: We tested whether tenecteplase, a recombinant fibrin-specific plasminogen activator can induce efficient thrombolysis in lower doses than the hitherto indicated, compared to full-dose therapy for vessel thrombosis.

Methods: Farm pigs (30-35 kg, n=23) were imposed in a clinically relevant model of common carotid-arteries (CA) and the left-anterior-descending (LAD) artery below the first diagonal occlusion. The vessels were initially externally injured followed by an appropriate for the vessel dose of thrombin. Occlusion was achieved in 80% for the LAD and 57% for the CA. Post occlusion the animals were allocated to one of the following groups: Group A) halfdose tenecteplase (2000IU); Group B) Full dose tenecteplase (5000IU); Group C) saline only. All animals received heparin and antiplatelet agents. The animals were followed-up for 120 minutes.

Results: Sixty minutes after thrombolysis recanalization occurred in 58% of the occluded arteries in Group A, in 85% in Group B and in 20% in Group C (P=0.028). Both tenecteplase regimens were effective for treating CA thrombosis (71% Group A vs 75% in Group B vs 33% in Group C, P=0.286), but low dose was significantly less effective in reestablishing flow in LADs (25% in Group A vs 100% in Group B vs 0% in Group C, P=0.015). Vessel patency was sustained for at least 1hr. In Group A, flow velocity in LAD reached 30% of the baseline value and 45% in carotids, while in Group B flow was 160% and 55% respectively. No differences in hemodynamic tested parameters and in post reperfusion arrhythmias were observed between the groups.

Conclusions: We developed a clinically relevant model useful for testing the efficacy of different thrombolytic regimens. Our data demonstrate that low dose tenecteplase can be successfully used for treating thrombosis of larger diameter vessels, such as the carotids, but appears inadequate for treating LAD thrombotic occlusions.