Document Detail

Partial inhibition of platelet thromboxane A2 synthesis by aspirin is associated with myonecrosis in patients with ST-segment elevation myocardial infarction.
MedLine Citation:
PMID:  17196455     Owner:  NLM     Status:  MEDLINE    
Heterogeneity in response to aspirin (ASA) treatment, or "aspirin resistance," could be of importance in patients with ST-segment elevation myocardial infarction (STEMI). Decreased effects of ASA in platelets could be due to partial inhibition of cyclo-oxygenase-1 (COX-1) or to COX-1-independent mechanisms. We evaluated the effect of ASA treatment in patients with STEMI for (1) platelet thromboxane A(2) (TXA(2)) synthesis, (2) platelet recruitment elicited by TXA(2)-dependent and -independent mechanisms, and (3) a possible association of these aspects of platelet reactivity with serum markers of myonecrosis. We studied 62 ASA-treated patients within 48 hours of onset of the acute event and 69 ASA-free and 10 ASA-treated controls. TXA(2) synthesis and platelet recruitment (fluid-phase proaggregate activity of cell-free releasate) were assessed after collagen stimulation (1 micro g/ml) of whole blood. Partial inhibition of TXA(2) by ASA was found in 21 patients (34%). This was associated with significant increases in troponin T, creatine kinase-MB mass, creatine kinase, and recruiting activity versus 41 patients with blocked TXA(2) production. This was independent of fibrinolysis, and platelet COX-2 expression was not augmented. TXA(2) blockade was achieved after subsequent daily treatments or platelet incubation with ASA in vitro, suggesting lower sensitivity of COX-1 to ASA. In addition, 28 patients (45%) had an abnormally increased recruiting activity despite TXA(2) blockade, which was also associated with increased myonecrosis. In conclusion, ASA resistance, elicited by TXA(2)-dependent and TXA(2)-independent mechanisms, was prevalent in patients with STEMI. This study describes, for the first time, the association of partial platelet TXA(2) inhibition with myonecrosis.
Juana Valles; M Teresa Santos; M Paz Fuset; Antonio Moscardo; Miguel Ruano; Francisca Perez; Marta Piñon; Silvia Breña; Justo Aznar
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-11-02
Journal Detail:
Title:  The American journal of cardiology     Volume:  99     ISSN:  0002-9149     ISO Abbreviation:  Am. J. Cardiol.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-01     Completed Date:  2007-02-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0207277     Medline TA:  Am J Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  19-25     Citation Subset:  AIM; IM    
Research Center, University Hospital La Fe, Valencia, Spain.
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MeSH Terms
Aged, 80 and over
Aspirin / administration & dosage,  therapeutic use*
Blood Platelets / physiology*
Case-Control Studies
Drug Resistance
Middle Aged
Myocardial Infarction / blood,  drug therapy*,  enzymology,  pathology
Myocardium / pathology
Platelet Aggregation / physiology
Platelet Aggregation Inhibitors / administration & dosage,  therapeutic use*
Severity of Illness Index
Thromboxane A2 / blood*
Reg. No./Substance:
0/Platelet Aggregation Inhibitors; 50-78-2/Aspirin; 57576-52-0/Thromboxane A2

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