Document Detail

Effect of time of 7E3 administration on rt-PA-induced reperfusion: study in a canine model of thrombus-based occlusion-reperfusion.
MedLine Citation:
PMID:  10422784     Owner:  NLM     Status:  MEDLINE    
Chimeric version of the murine monoclonal antibody, 7E3 has been proposed for the early restoration of coronary artery patency during thrombolytic therapy. We determined the optimal time for administration of 7E3 during recombinant tissue plasminogen activator (rt-PA)-induced thrombolysis using a canine model of coronary artery thrombosis. After 30 min of thrombotic occlusion, microspheres were injected to assess regional myocardial blood flow, followed by a 90-min rt-PA infusion. Dogs were randomized to three groups wherein 7E3 (0.8 mg kg(-1), i.v.) was administered either 5 min before rt-PA (Group I), at the first evidence of thrombolysis (Group II), or after the completion of rt-PA infusion (Group III). Hemodynamic parameters were monitored for 6 h after which infarct size was estimated. Time to occlusion/reperfusion was similar in all groups. In the rt-PA alone group, 78% arteries reoccluded after 60 min of reperfusion. The incidence of reocclusion was lower in Groups II (25%, P = 0.04) and III (0%. P < 0.01). All arteries (100%) were patent at the end of the protocol in Group III vs 50% remaining patent in Group I (P = 0.01). Arterial patency was maintained longer in Group III (301 min, n = 10), compared with Groups I (124 min, n = 5) and II (124 min, n = 6). Arterial flow was greater in Group III (82%) compared with Groups I (27%) and II (35%) (P < 0.01). Regional myocardial blood flow and infarct size were similar in all groups. The data indicate that the time of administration of 7E3 in conjunction with rt-PA-induced thrombolysis influences patency status. The experimental results suggest that in the absence of aspirin and heparin, optimal thrombolysis is obtained when 7E3 is administered after the completion of rt-PA infusion regimen.
S S Rebello; J Huang; K Saito; J F Saucedo; E R Bates; B R Lucchesi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of pharmacology     Volume:  374     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1999 Jun 
Date Detail:
Created Date:  1999-09-13     Completed Date:  1999-09-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  399-410     Citation Subset:  IM    
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0632, USA.
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MeSH Terms
Antibodies, Monoclonal / administration & dosage,  therapeutic use*
Blood Coagulation / drug effects
Coronary Circulation / drug effects
Coronary Thrombosis / drug therapy,  mortality,  physiopathology
Coronary Vessels / drug effects,  physiopathology
Disease Models, Animal
Drug Administration Schedule
Drug Therapy, Combination
Myocardial Infarction / drug therapy,  physiopathology
Myocardial Reperfusion*
Partial Thromboplastin Time
Prothrombin Time
Recombinant Proteins / therapeutic use
Regional Blood Flow / drug effects
Thrombolytic Therapy
Time Factors
Tissue Plasminogen Activator / therapeutic use*
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Recombinant Proteins; EC Plasminogen Activator

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