Monoclonal antibody against the platelet glycoprotein (GP) IIb/IIIa receptor prevents coronary artery reocclusion after reperfusion with recombinant tissue-type plasminogen activator in dogs
Autor: | Robert C. Leinbach, D. Collen, L E Scudder, J L Guerrero, Michito Kanke, Tsunehiro Yasuda, John T. Fallon, M J Ross, D Shealy, Herman K. Gold |
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Rok vydání: | 1988 |
Předmět: |
medicine.medical_specialty
Platelet Aggregation medicine.medical_treatment Coronary Disease Receptors Cell Surface Platelet Membrane Glycoproteins Tissue plasminogen activator Immunoglobulin Fab Fragments Dogs Internal medicine medicine Animals Platelet Thrombus Aspirin business.industry Coronary Thrombosis Antibodies Monoclonal Dipyridamole General Medicine Thrombolysis medicine.disease Thrombosis Surgery Coronary arteries medicine.anatomical_structure Tissue Plasminogen Activator Microscopy Electron Scanning Cardiology business Plasminogen activator Research Article medicine.drug |
Zdroj: | Journal of Clinical Investigation. 81:1284-1291 |
ISSN: | 0021-9738 |
Popis: | Localized thrombosis was produced in the left anterior descending (LAD) coronary artery of open chest dogs by constricting a segment so as to produce greater than 90% stenosis (reducing blood flow to 40 +/- 10% of baseline), and placing a thrombus in the segment immediately proximal to the stenosis by inducing endothelial cell injury and instilling a mixture of blood and thrombin. Intravenous infusion of recombinant tissue-type plasminogen activator (rt-PA) at a rate of 15-30 micrograms/kg per min for 30 or 60 min in eight dogs induced coronary artery reperfusion within 23 +/- 7 min (mean +/- SD), but reocclusion occurred despite heparin anticoagulation in all but one of these dogs within 7 +/- 5 min. Intravenous injection of 0.8 mg/kg of the F(ab')2 fragment of a monoclonal antibody (7E3) directed against the platelet GPIIb/IIIa receptor, prevented reocclusion in 10/10 dogs during an observation period of 2 h (P less than 0.001 vs. rt-PA alone). The antibody abolished ADP-induced platelet aggregation and markedly prolonged the bleeding time. Intravenous aspirin or dipyridamole prevented reocclusion for 1 h or more in only 2/7 and 1/6 dogs, respectively. We conclude that the monoclonal antibody is very effective in preventing reocclusion after successful thrombolysis of occluded coronary arteries with rt-PA. |
Databáze: | OpenAIRE |
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