Optimal suppression of thromboxane A(2) formation by aspirin during percutaneous transluminal coronary angioplasty: no additional effect of a selective cyclooxygenase-2 inhibitor.
J Am Coll Cardiol
; 43(4): 526-31, 2004 Feb 18.
Article
em En
| MEDLINE
| ID: mdl-14975458
ABSTRACT
OBJECTIVES:
We examined the contribution of cyclooxygenase (COX)-1 and -2 to the generation of prostacyclin, thromboxane (Tx) A(2), and 8-epi prostaglandin (PG) F(2alpha) during percutaneous transluminal coronary angioplasty (PTCA).BACKGROUND:
Both TxA(2) and 8-epi PGF(2alpha) activate platelets and are mitogenic, whereas prostacyclin is a platelet inhibitor, and therefore may influence the outcome of PTCA.METHODS:
Twenty-one patients undergoing PTCA while receiving aspirin 300 mg daily or aspirin plus the selective COX-2 inhibitor nimesulide were compared with 13 patients treated only with fradafiban, a glycoprotein IIb/IIIa antagonist. Urine was analyzed for the metabolites of TxA(2) (Tx-M) and prostacyclin (PGI-M) and for the isoprostane, 8-epi PGF(2alpha).RESULTS:
In the fradafiban group, there was a marked increase in Tx-M during PTCA (mean, 1973; 95% confidence interval [CI] 112 to 3834 rising to mean 7645; 95% CI 2,009 to 13281 pg/mg creatinine, p = 0.018). The Tx-M excretion was similarly reduced by aspirin and the combination of aspirin and nimesulide. In contrast, the combination of nimesulide and aspirin inhibited PGI-M excretion to a greater extent than aspirin (p = 0.001). Urinary 8-epi PGF(2alpha) excretion was elevated following PTCA compared with normal subjects (p = 0.002) and appeared to be unaffected by any of the treatments.CONCLUSIONS:
The increase in TxA(2) during PTCA is primarily COX-1 dependent, and aspirin alone is effective in suppressing its formation. In contrast, prostacyclin generation is both COX-1 and COX-2 dependent. The inhibition of COX-1 and COX-2 did not prevent the production of 8-epi PGF(2alpha), suggesting that this is not enzymatically derived. The persistent generation of 8-epi PGF(2alpha) may contribute to the thrombosis and restenosis that complicate PTCA.
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Base de dados:
MEDLINE
Assunto principal:
Pirrolidinas
/
Sulfonamidas
/
Tromboxano A2
/
Compostos de Bifenilo
/
Inibidores da Agregação Plaquetária
/
Dinoprosta
/
Angioplastia Coronária com Balão
/
Aspirina
/
Epoprostenol
/
Isoenzimas
Tipo de estudo:
Clinical_trials
Limite:
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article