Antithrombotic efficacy of a novel murine antihuman factor IX antibody in rats
| Autor: | Giora Z. Feuerstein, William R. Church, Paul F. Koster, Arun Patel, Peter J. Bugelski, Andrew J. Nichols, Richard E. Valocik, John R. Toomey, Michael N. Blackburn, Audrey Baker |
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| Rok vydání: | 1999 |
| Předmět: |
Male
medicine.medical_specialty medicine.drug_class Iron Blood Loss Surgical Dose-Response Relationship Immunologic Arterial Occlusive Diseases Pharmacology Factor IX Rats Sprague-Dawley Bolus (medicine) Fibrinolytic Agents Medicine Animals Humans Anesthesia Artery occlusion Thrombus medicine.diagnostic_test Aspirin business.industry Heparin Anticoagulant Antibodies Monoclonal Anticoagulants Surgical wound Thrombosis medicine.disease Surgery Rats Disease Models Animal Carotid Arteries Hemostasis Immunoglobulin G Microscopy Electron Scanning Prothrombin Time Partial Thromboplastin Time Cardiology and Cardiovascular Medicine business Partial thromboplastin time |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology. 19(10) |
| ISSN: | 1079-5642 |
| Popis: | Abstract —A murine antihuman factor IX monoclonal antibody (BC2) has been generated and evaluated for its capacity to prolong the activated partial thromboplastin time (aPTT) in vitro and ex vivo and to prevent arterial thrombosis in a rat model in vivo. BC2 extended aPTT to a maximum of 60 to 80 seconds at 100 to 1000 nmol/L in vitro (rat and human plasma, respectively) and ex vivo (rat) after dosing of rats up to 6 mg/kg in vivo. BC2, administered as bolus (1 to 6 mg/kg) followed by infusion (0.3 to 2 mg · kg −1 · h −1 ), dose-dependently prevented thrombosis of an injured rat carotid artery (FeCl 3 -patch model), increased time to artery occlusion, and reduced incidence of vessel occlusion. BC2 efficacy in preventing arterial thrombosis exceeded that of heparin (bolus 15 to 120 U/kg followed by infusion 0.5 to 4.0 U · kg −1 · min −1 ), whereas the latter rendered the blood incoagulable (aPTT>1000 seconds). BC2 demonstrated complete antithrombotic efficacy also as a single bolus given either as prevessel or postvessel injury as evidenced by reduction of thrombus mass (from 4.18±0.49 to 1.80±0.3 mg, P P P P P |
| Databáze: | OpenAIRE |
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