Document Detail


Prevention of rethrombosis after coronary thrombolysis in a chronic canine model. I. Adjunctive therapy with monoclonal antibody 7E3 F(ab')2 fragment.
MedLine Citation:
PMID:  7511747     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We examined the efficacy of the monoclonal antibody (MoAb) 7E3 F(ab')2 fragment, an inhibitor of the platelet glycoprotein (GP)IIb/IIIa receptor, to prevent coronary artery rethrombosis after successful thrombolysis with rt-PA. The circumflex coronary artery of anesthetized dogs was instrumented with a flow probe, an electrode, and a stenosis. After recovery from the surgical procedure, the animals were reanesthetized on post-operative day 9, and vessel wall injury was induced with current applied to the intimal surface of the circumflex coronary artery. The resulting occlusive thrombus was aged for 30 min, and recombinant tissue plasminogen activator (rt-PA) was administered. The animals were allocated to receive either placebo or a single dose of 7E3 [0.8 mg/kg intravenous (i.v.) bolus] as the sole adjunctive agent. Ex vivo platelet function and coronary artery blood flow velocity were recorded on each of 5 consecutive days. Reocclusion and mortality were reduced significantly in animals treated with 7E3 as compared with the placebo-treated group. Significant inhibition of ex vivo platelet aggregation persisted for 48 h after a single injection of 7E3. The MoAb 7E3 F(ab')2 fragment is effective as the sole adjunctive agent with rt-PA for prevention of rethrombosis. The present study is unique in that it examined the efficacy of GPIIb/IIIa inhibition in an experimental model for an extended time, demonstrating the duration of antiplatelet therapy required to prevent rethrombosis after thrombolysis.
Authors:
W E Rote; D X Mu; E R Bates; M A Nedelman; B R Lucchesi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of cardiovascular pharmacology     Volume:  23     ISSN:  0160-2446     ISO Abbreviation:  J. Cardiovasc. Pharmacol.     Publication Date:  1994 Feb 
Date Detail:
Created Date:  1994-05-05     Completed Date:  1994-05-05     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7902492     Medline TA:  J Cardiovasc Pharmacol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  194-202     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48108-0626.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antibodies, Monoclonal / therapeutic use*
Blood Coagulation / drug effects
Chronic Disease
Coronary Circulation / physiology
Coronary Thrombosis / pathology,  physiopathology,  prevention & control*
Coronary Vessels / pathology,  physiopathology
Dogs
Electrocardiography
Fibrinolytic Agents / therapeutic use*
Immunoglobulin Fab Fragments / therapeutic use*
Male
Myocardial Infarction / pathology,  physiopathology
Platelet Aggregation / drug effects
Platelet Membrane Glycoproteins / metabolism
Recurrence
Tissue Plasminogen Activator / therapeutic use
Grant Support
ID/Acronym/Agency:
HL-19782-15/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Fibrinolytic Agents; 0/Immunoglobulin Fab Fragments; 0/Platelet Membrane Glycoproteins; EC 3.4.21.68/Tissue Plasminogen Activator

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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