6-ketoprostaglandin-f1-alpha and Lung-Diseases--Obstructive

Patients with Down syndrome (DS) and a left-to-right shunt often develop early severe pulmonary hypertension (PH) and pulmonary vascular obstructive disease (PVOD); the pathophysiological mechanisms underlying the development of these complications are yet to be determined. To investigate the mechanisms, we evaluated the biosynthesis of thromboxane (TX) A(2) and prostacyclin (PGI(2)) in four groups of infants, cross-classified as shown below, by measuring the urinary excretion levels of 11-dehydro-TXB(2) and 2,3-dinor-6-keto-PGF(1alpha): DS infants with a left-to-right shunt and PH (D-PH, n = 18), DS infants without congenital heart defect (D-C, n = 8), non-DS infants with a left-to-right shunt and PH (ND-PH, n = 12), and non-DS infants without congenital heart defect (ND-C, n = 22). The urinary excretion ratios of 11-dehydro-TXB(2) to 2,3-dinor-6-keto-PGF(1alpha) in the D-PH, D-C, ND-PH, and ND-C groups were 7.69, 4.71, 2.10, and 2.27, respectively. The ratio of 11-dehydro-TXB(2) to 2,3-dinor-6-keto-PGF(1alpha) was higher in the presence of DS (P < 0.001), independently of the presence of PH (P = 0.297). The predominant biosynthesis of TXA(2) over PGI(2), leading to vasoconstriction, was observed in DS infants, irrespective of the presence/absence of PH. This imbalance in the biosynthesis of vasoactive eicosanoids may account for the rapid progression of PVOD in DS infants with a left-to-right shunt.

Topics: 6-Ketoprostaglandin F1 alpha; Child, Preschool; Cross-Sectional Studies; Down Syndrome; Epoprostenol; Female; Heart Defects, Congenital; Humans; Hypertension, Pulmonary; Infant; Lung Diseases, Obstructive; Male; Prognosis; Pulmonary Heart Disease; Radioimmunoassay; Thromboxane A2; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Epoprostenol; Humans; Hypertension, Pulmonary; Lung Diseases, Obstructive; Thromboxane B2

Fourteen experimental indices were determined in 26 patients of chronic cor pulmonale due to COPD and in 32 healthy nonsmokers. It was found that elastase, TXB2, ATII, 5-HT, IgE, CTC and Ach were significantly higher whereas 6-keto -PGF1 alpha, C4 and cAMP lower in the blood from the patients. The roles played by these factors in the development of chronic cor pulmonale were discussed.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Angiotensin II; Antigen-Antibody Complex; Complement C4; Female; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Pancreatic Elastase; Pulmonary Heart Disease; Serotonin; Thromboxane B2

Constriction of small pulmonary arteries and arterioles and focal vascular injury are features of pulmonary hypertension. Because thromboxane A2 is both a vasoconstrictor and a potent stimulus for platelet aggregation, it may be an important mediator of pulmonary hypertension. Its effects are antagonized by prostacyclin, which is released by vascular endothelial cells. We tested the hypothesis that there may be an imbalance between the release of thromboxane A2 and prostacyclin in pulmonary hypertension, reflecting platelet activation and an abnormal response of the pulmonary vascular endothelium.. We used radioimmunoassays to measure the 24-hour urinary excretion of two stable metabolites of thromboxane A2 and a metabolite of prostacyclin in 20 patients with primary pulmonary hypertension, 14 with secondary pulmonary hypertension, 9 with severe chronic obstructive pulmonary disease (COPD) but no clinical evidence of pulmonary hypertension, and 23 normal controls.. The 24-hour excretion of 11-dehydro-thromboxane B2 (a stable metabolite of thromboxane A2) was increased in patients with primary pulmonary hypertension and patients with secondary pulmonary hypertension, as compared with normal controls (3224 +/- 482, 5392 +/- 1640, and 1145 +/- 221 pg per milligram of creatinine, respectively; P less than 0.05), whereas the 24-hour excretion of 2,3-dinor-6-keto-prostaglandin F1 alpha (a stable metabolite of prostacyclin) was decreased (369 +/- 106, 304 +/- 76, and 644 +/- 124 pg per milligram of creatinine, respectively; P less than 0.05). The rate of excretion of all metabolites in the patients with COPD but no clinical evidence of pulmonary hypertension was similar to that in the normal controls.. An increase in the release of the vasoconstrictor thromboxane A2, suggesting the activation of platelets, occurs in both the primary and secondary forms of pulmonary hypertension. By contrast, the release of prostacyclin is depressed in these patients. Whether the imbalance in the release of these mediators is a cause or a result of pulmonary hypertension is unknown, but it may play a part in the development and maintenance of both forms of the disorder.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Epoprostenol; Female; Humans; Hypertension, Pulmonary; Lung Diseases, Obstructive; Male; Radioimmunoassay; Thromboxane A2; Thromboxane B2

We measured the pulmonary arterial pressure and the level of Thromboxane A2 (TXA2), and Prostacyclin (PGI2) in 30 stable COPD patients and the level of TXA2 and PGI2 in 10 normal subjects so as to investigate the changes of TXA2 and PGI2 in COPD patients with pulmonary hypertension. The results showed that the level of TXA2 increased significantly in COPD patients with dominant and latent pulmonary hypertension when compared with that in normal subjects (P less than 0.001, less than 0.01), and the level of TXA2 in COPD patients with dominant pulmonary hypertension was also higher than that in COPD patients with latent pulmonary hypertension (P less than 0.02), but there was no difference in the level of PGI2 among normal subjects and COPD patients with or without pulmonary hypertension. This indicates that TXA2 plays an important role in causing pulmonary hypertension in COPD patients.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Female; Humans; Hypertension, Pulmonary; Lung Diseases, Obstructive; Male; Middle Aged; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Aspirin; Blood Platelets; Female; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Physical Exertion; Platelet Aggregation; Smoking; Thromboxane B2