Monoclonal antibody against tissue factor shortens tissue plasminogen activator lysis time and prevents reocclusion in a rabbit model of carotid artery thrombosis
| Autor: | I Pascucci, Davide D’Andrea, Paolo Golino, Massimo Ragni, Michael D. Ezekowitz, Massimo Chiariello, Nicola Eramo, Aruna Pawashe, Annalisa Scognamiglio, Plinio Cirillo |
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| Přispěvatelé: | Ragni, M, Cirillo, P, Pascucci, I, Scognamiglio, A, Dandrea, D, Eramo, N, Ezekowitz, Md, Pawashe, Ab, Chiariello, M, Golino, Paolo, Cirillo, Plinio, Pascucci, Immacolata, D’Andrea, D, Ezekowitz, M, Chiariello, Massimo, Golino, P. |
| Předmět: |
Male
medicine.medical_specialty Platelet Aggregation medicine.medical_treatment Tissue plasminogen activator Thromboplastin Tissue factor Plasminogen Activators Restenosis Physiology (medical) Internal medicine medicine Animals Carotid Artery Thrombosis coagulation Thrombus Fibrinopeptide A business.industry Antibodies Monoclonal Fibrinogen Thrombolysis Heparin tissue factor medicine.disease Surgery Tissue Plasminogen Activator Cardiology thrombolysi Female Rabbits Cardiology and Cardiovascular Medicine business Plasminogen activator medicine.drug |
| Zdroj: | Scopus-Elsevier |
| Popis: | Background Tissue factor (TF)–dependent activation of the coagulation is important in the pathophysiology of intravascular thrombus formation. We tested the effects of a monoclonal antibody against TF (AP-1) on lysis time induced by tissue-type plasminogen activator (TPA) and on reocclusion rate in a rabbit model of carotid artery thrombosis. Methods and Results Intravascular thrombosis was obtained by placing an external constrictor around carotid arteries with endothelial injury. Carotid blood flow velocity was measured continuously with a Doppler flow probe. Thirty minutes after thrombus formation, the rabbits received either AP-1 (0.15 mg/kg IV, n=8) or placebo (n=8). All rabbits also received TPA (80 μg/kg bolus plus 8 μg·kg −1 ·min −1 infusion for up to 90 minutes or until reperfusion was achieved) and heparin (200 U/kg IV as a bolus). At reperfusion, TPA was discontinued, and the rabbits were followed for an additional 90 minutes. AP-1 shortened lysis time from 44±8 minutes (mean±SEM) in control rabbits to 26±7 minutes in AP-1–treated rabbits ( P P Conclusions TF exposure and activation of the extrinsic coagulation pathway play an important role in prolonging lysis time and mediating reocclusion after thrombolysis in this model. AP-1, a monoclonal antibody against TF, might be suitable as adjunctive therapy to TPA. |
| Databáze: | OpenAIRE |
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