Modulation of Aspirin-Insensitive Eicosanoid Biosynthesis by 6-Methylprednisolone in Unstable Angina
| Autor: | Paola Patrignani, Massimo Pasquale, Franco Cuccurullo, M. R. Panara, Anita Greco, A. Ganci, Domenico Di Gregorio, Andrea Mezzetti, Francesco Cipollone, Ettore Porreca |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Adult
Blood Platelets Male medicine.medical_specialty Thromboxane Myocardial Ischemia Chest pain Placebo Methylprednisolone Angina Thromboxane A2 chemistry.chemical_compound Double-Blind Method Physiology (medical) Internal medicine medicine Humans Cyclooxygenase Inhibitors Angina Unstable Glucocorticoids Leukotriene E4 Aspirin Unstable angina business.industry Middle Aged medicine.disease Thromboxane B2 chemistry Anesthesia Cardiology Eicosanoids Female medicine.symptom Cardiology and Cardiovascular Medicine business medicine.drug |
| Zdroj: | Circulation. 107:55-61 |
| ISSN: | 1524-4539 0009-7322 |
| DOI: | 10.1161/01.cir.0000043260.82447.62 |
| Popis: | Background— The evidence that inflammation plays a pivotal role in the pathophysiology of acute coronary syndromes prompted us to investigate the effects of glucocorticoid treatment on leukotriene (LT) C 4 and thromboxane (TX) A 2 biosynthesis in unstable angina. Methods and Results— Urinary LTE 4 and 11-dehydro-TXB 2 were significantly higher in 12 patients with unstable angina than in 12 patients with stable angina and 12 patients with nonischemic chest pain. Furthermore, we randomized the unstable angina patients to receive intravenous 6-methylprednisolone (6-MP; 1 mg/kg BID for 2 days) or matching placebo and collected 12 consecutive 6-hour urine samples before and during the infusions. LTE 4 excretion showed a time-dependent decrease in the 6-MP group but did not decrease during placebo. Furthermore, during myocardial ischemia, LTE 4 was significantly higher before 6-MP infusion than during steroid therapy. In contrast, 11-dehydro-TXB 2 did not differ significantly during 6-MP versus placebo. Myocardial ischemia elicited by stress test in the stable angina patients was not accompanied by any change in LTE 4 and 11-dehydro-TXB 2 , thus ruling out a role of ischemia per se in the induction of increased eicosanoid production. Conclusions— Increased production of vasoactive LT and TX may occur in unstable angina despite conventional antithrombotic and antianginal treatment. Glucocorticoids can suppress LTC 4 biosynthesis in the short term and may provide an interesting tool to explore the pathophysiological significance of inflammatory cell activation in this setting. |
| Databáze: | OpenAIRE |
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