2-3-dinor-6-ketoprostaglandin-f1alpha and Myocardial-Infarction

Heavy binge drinking may trigger the onset of embolic stroke and acute myocardial infarction, but the underlying mechanisms are unclear. The effects of binge drinking on the hemostatic system and its circadian variation have not been investigated. We investigated the effects of an acute intake of a large dose of alcohol (1.5 g/kg).. Twelve healthy, nonsmoking men participated in sessions where they were served ethanol in fruit juice or served fruit juice alone and, lying in a supine position, were followed up for 12 to 24 hours. The treatments were randomized and separated from each other by a 1-week washout period. Blood and urine were collected for hemostatic measurements.. The urinary excretion of the platelet thromboxane A(2) metabolite 2, 3-dinor-thromboxane B(2) was significantly (P<0.05) greater during the night after an evening intake of alcohol than during the control night. A smaller increase was observed during the daytime after an intake of alcohol in the morning. The effects on the endothelial prostacyclin metabolite 2,3-dinor-6-ketoprostaglandin F(1alpha) excretion were negligible. A 7-fold increase in plasminogen activator inhibitor 1 activity was observed after both morning (P<0. 05) and evening (P<0.01) intakes of alcohol.. This is the first study to suggest that acute ingestion of a relatively large but tolerable dose of alcohol transiently enhances thromboxane-mediated platelet activation. The observations also demonstrate alcohol-induced changes in the normal circadian periodicity of the hemostatic system in subjects not accustomed to consumption of alcohol.

Topics: 6-Ketoprostaglandin F1 alpha; Acute Disease; Adult; Alcoholic Intoxication; Biomarkers; Circadian Rhythm; Creatinine; Cross-Over Studies; Disease Susceptibility; Drug Administration Schedule; Ethanol; Fibrinolysis; Hemorheology; Hemostasis; Humans; Male; Myocardial Infarction; Plasminogen Activator Inhibitor 1; Platelet Activation; Platelet Aggregation; Stroke; Supine Position; Thromboxane B2

A genetic variant (rs20417) of the PTGS2 gene, encoding for COX-2, has been associated with decreased COX-2 activity and a decreased risk of cardiovascular disease (CVD). However, this genetic association and the role of COX-2 in CVD remain controversial.. The association of rs20417 with CVD was prospectively explored in 49 232 subjects (ACTIVE-A, CURE, epiDREAM/DREAM, ONTARGET, RE-LY, and WGHS) and the effect of potentially modifiable risk factors on the genetic association was further explored in 9363 INTERHEART participants. The effect of rs20417 on urinary thromboxane and prostacyclin metabolite concentrations was measured in 117 healthy individuals. Carriage of the rs20417 minor allele was associated with a decreased risk of major CVD outcomes (OR = 0.78, 95% CI: 0.70-0.87; P = 1.2 × 10(-5)). The genetic effect was significantly stronger in aspirin users (OR: 0.74, 95% CI: 0.64-0.84; P = 1.20 × 10(-5)) than non-users (OR: 0.87, 95% CI: 0.72-1.06; P = 0.16) (interaction P-value: 0.0041). Among patients with previous coronary artery disease (CAD), rs20417 carriers had a stronger protective effect on risk of major adverse events when compared with individuals without previous CAD (interaction P-value: 0.015). Carriers had significantly lower urinary levels of thromboxane (P = 0.01) and prostacyclin (P = 0.01) metabolites when compared with non-carriers.. The rs20417 polymorphism is associated with a reduced risk of major cardiovascular events and lower levels of thromboxane and prostacyclin. Our results suggest that a genetic decrease in COX-2 activity may be beneficial with respect to CVD risk, especially, in higher risk patients on aspirin.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Aspirin; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Female; Heterozygote; Humans; Male; Multicenter Studies as Topic; Myocardial Infarction; Polymorphism, Genetic; Prospective Studies; Randomized Controlled Trials as Topic; Stroke; Thromboxane B2

Thirty-two patients with acute myocardial infarction performed an exercise stress test one month after hospital discharge. The in vivo formation of thromboxane and prostacyclin formation before and during the exercise stress test was analyzed with gas chromatography-mass spectrometry of the in vivo formed metabolites 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha. Patients with a significant increase in thromboxane formation (> 30%) during exercise (P < 0.0001) had a worse prognosis, with a 60% incidence of coronary events during the three years following the index infarction as compared to only 8% in the group without such an increase in thromboxane formation during exercise (P = 0.008). The group with coronary events and increased thromboxane formation included patients not detected by classical risk factors. Our findings suggest that exercise-induced thromboxane formation in survivors of an acute myocardial infarction may include prognostic information not defined by other risk indicators.

Topics: 6-Ketoprostaglandin F1 alpha; Adrenergic beta-Antagonists; Adult; Aged; Aspirin; Epoprostenol; Exercise; Exercise Test; Female; Gas Chromatography-Mass Spectrometry; Humans; Male; Middle Aged; Myocardial Infarction; Prognosis; Thromboxane A2; Thromboxane B2

Twenty-five patients with myocardial infarction were monitored in the acute phase and during follow-up with regard to the in vivo production of prostacyclin (PGI2) and thromboxane (TxA2), by measurement of their major urinary metabolites, 2,3-dinor-6-keto-PGF1 alpha and 2,3-dinor-TxB2, respectively. In 22 of these patients PGI2 and TxA2 production were also assessed before, during and after an exercise test performed 6 weeks after discharge. In approximately 24% of patients the in vivo production of prostacyclin did not increase during the acute phase of the infarction process. This inability was usually associated with a decrease in the release of heart muscle enzymes, and was mostly frequently observed in women. During the exercise tolerance test, none of the patients showed any increase in prostacyclin production, in contrast to healthy volunteers, in whom a significant increase was seen. There were no differences between patients with and without an increase in prostacyclin production during the acute phase. At the follow-up 2 years after the myocardial infarction, eight cardiac events had occurred, all of which were noted among patients who exhibited an expected increase in prostacyclin production in association with the infarction. This would seem reasonable, since most of the patients in this group had larger primary infarctions.

Topics: 6-Ketoprostaglandin F1 alpha; Aged; Creatine Kinase; Epoprostenol; Exercise Test; Female; Follow-Up Studies; Humans; Isoenzymes; Male; Middle Aged; Monitoring, Physiologic; Myocardial Infarction; Thromboxane A2; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Epoprostenol; Humans; Myocardial Infarction; Thromboxanes

Topics: 6-Ketoprostaglandin F1 alpha; Anti-Inflammatory Agents, Non-Steroidal; Benzofurans; Blood Vessel Prosthesis; Epoprostenol; Gas Chromatography-Mass Spectrometry; Humans; Myocardial Infarction; Thromboxane A2; Thromboxane B2

The in vivo production of prostacyclin and thromboxane was monitored by measuring their major urinary metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha in ten patients with acute myocardial infarction, five on standard treatment and five receiving prostacyclin infusion. During acute myocardial infarction excretion of 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1 alpha, measured by a gas chromatography-mass spectrometry method with deuterated internal standards, was significantly increased. This indicates that thromboxane and prostacyclin synthesis are increased during the development of acute myocardial infarction. The excretion data for 2,3-dinor-thromboxane B2 showed that after administration of aspirin there was less pronounced and more variable inhibition than expected. Prostacyclin infusion did not markedly affect the excretion of the thromboxane metabolite.

Topics: 6-Ketoprostaglandin F1 alpha; Epoprostenol; Humans; Infusions, Parenteral; Myocardial Infarction; Thromboxane B2; Thromboxanes

Pathological and clinical studies have suggested that platelets have a role in the pathogenesis of unstable angina and myocardial infarction. However, the relation of platelet activation to episodic ischemia in patients with unstable angina is unknown. We assessed the biosynthesis of thromboxane and prostacyclin as indexes of platelet activation in patients with stable and unstable coronary disease by physicochemical analysis of metabolites in plasma and urine. Prostacyclin biosynthesis was markedly elevated in patients with acute myocardial infarction and correlated with plasma creatine kinase (r = 0.795; P less than 0.001). The largest rise in thromboxane synthesis was observed in patients with unstable angina, in whom 84 percent of the episodes of chest pain were associated with phasic increases in the excretion of thromboxane and prostacyclin metabolites. However, 50 percent of such increases were not associated with chest pain, possibly reflecting silent myocardial ischemia. These data indicate that platelet activation occurs during spontaneous ischemia in patients with unstable angina. The increment in prostacyclin biosynthesis during such episodes may be a compensatory response of vascular endothelium that limits the degree or effects of platelet activation. If so, biochemically selective inhibition of the synthesis or action of thromboxane A2 would be desirable in the treatment of unstable angina. In contrast, thromboxane inhibitors or antagonists would not be expected to be effective in patients with chronic stable angina, in whom there was no increase in the formation of thromboxane A2.

Topics: 6-Ketoprostaglandin F1 alpha; Angina Pectoris; Angina, Unstable; Blood Platelets; Epoprostenol; Humans; Myocardial Infarction; Thromboxane A2; Thromboxane B2