Document Detail


Does tissue-type plasminogen activator have direct beneficial effects on the myocardium independent of its ability to lyse intracoronary thrombi?
MedLine Citation:
PMID:  2496937     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tissue-type plasminogen activator (t-PA) is a widely used thrombolytic agent for treating acute myocardial infarction. Some previous studies suggest that t-PA benefits the heart independently of lysing coronary artery thrombi. The purpose of this study was to determine whether t-PA directly affects infarct size independently of lysing coronary thrombi, affects the no-reflow phenomenon, and exacerbates intramyocardial hemorrhage. We used a canine model of 2 hours of occlusion of the left anterior descending coronary artery followed by 4 hours of reperfusion. t-PA was administered 30 minutes after occlusion and was continued for 2 hours. Myocardial infarct size as a percentage of the risk zone was similar between saline (28 +/- 8%) and t-PA (35 +/- 9%) groups in a low-dose study and between saline (46 +/- 12%) and t-PA (44 +/- 12%) groups in a high-dose study. t-PA did not improve no-reflow. Intramyocardial hemoglobin level within the infarct was similar between saline (16 micrograms/mg) and high-dose t-PA (12 micrograms/mg) groups. The extent of hemorrhage assessed by intramyocardial hemoglobin correlated with infarct size. Histologic evaluation revealed that microscopic hemorrhage was confined to zones of contraction band necrosis. Neutrophil infiltration during early reperfusion was prominent. In conclusion, t-PA did not directly benefit the myocardium or no-reflow. Its effects in patients are likely due to its ability to lyse thrombi. t-PA did not cause infiltration of hemorrhage into noninfarcted tissue. Reperfusion accelerates the inflammatory response after myocardial infarction and results in early, intense neutrophil infiltration.
Authors:
R A Kloner; K Alker; C Campbell; G Figures; A Eisenhauer; S Hale
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Circulation     Volume:  79     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1989 May 
Date Detail:
Created Date:  1989-06-09     Completed Date:  1989-06-09     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1125-36     Citation Subset:  AIM; IM    
Affiliation:
Division of Cardiology, Wayne State University, Detroit, Michigan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Coronary Disease / drug therapy*
Coronary Thrombosis / drug therapy*
Dogs
Female
Heart / drug effects*
Male
Myocardial Infarction / drug therapy*
Myocardial Reperfusion / methods
Myocardium / pathology
Neutrophils / pathology
Recombinant Proteins / therapeutic use
Time Factors
Tissue Plasminogen Activator / therapeutic use*
Chemical
Reg. No./Substance:
0/Recombinant Proteins; 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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