Abstract
BACKGROUND--Children with cyanotic congenital heart disease and pulmonary outflow tract obstruction have shortened platelet survival times and are susceptible to thrombosis and organ infarction. Thromboxane A2 and prostacyclin have opposing actions on platelet aggregability and an imbalance in their biosynthesis might contribute to the pathophysiology of these complications. METHODS--Biosynthesis of thromboxane A2 and prostacyclin was investigated in 16 children (4-32 months, median 18 months) with cyanotic congenital heart disease and pulmonary outflow tract obstruction and compared with 16 healthy children of a similar age (6-34 months, median 24 months). Urinary excretion of 2,3-dinor-thromboxane B2 (a metabolite of thromboxane A2) and of 2,3-dinor-6-oxo-prostaglandin F1 alpha (a metabolite of prostacyclin) was measured. RESULTS--The children with cyanotic congenital heart disease and pulmonary outflow tract obstruction excreted more 2,3-dinor-thromboxane B2 than the healthy children: 916(163) compared with 592(122) ng/g creatinine (mean(SEM); 2p = 0.014). The ratio of excretion of 2,3-dinor-thromboxane B2 to 2,3-dinor-prostaglandin F1 alpha was greater in the patients than in the healthy control group (2.38(0.28) v 1.3(0.22)) (2p = 0.002). CONCLUSION--The balance between biosynthesis of prostacyclin and of thromboxane A2 is abnormal in children with cyanotic congenital heart disease and pulmonary outflow tract obstruction and favours platelet aggregation and vasoconstriction.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- BEST P. V., HEATH D. Pulmonary thrombosis in cyanotic congenital heart disease without pulmonary hypertension. J Pathol Bacteriol. 1958 Apr;75(2):281–291. doi: 10.1002/path.1700750206. [DOI] [PubMed] [Google Scholar]
- Barrow S. E., Ritter J. M. Prostacyclin biosynthesis in vivo: measurements in plasma and urine. Prostaglandins Leukot Essent Fatty Acids. 1988;33(3):213–220. doi: 10.1016/0952-3278(88)90033-6. [DOI] [PubMed] [Google Scholar]
- Barrow S. E., Ward P. S., Sleightholm M. A., Ritter J. M., Dollery C. T. Cigarette smoking: profiles of thromboxane- and prostacyclin-derived products in human urine. Biochim Biophys Acta. 1989 Oct 13;993(1):121–127. doi: 10.1016/0304-4165(89)90151-7. [DOI] [PubMed] [Google Scholar]
- Bjøro K., Haugen G., Stray-Pedersen S. Altered prostanoid formation in human umbilical vasculature in response to variations in oxygen tension. Prostaglandins. 1987 Sep;34(3):377–384. doi: 10.1016/0090-6980(87)90083-9. [DOI] [PubMed] [Google Scholar]
- FitzGerald G. A., Brash A. R., Falardeau P., Oates J. A. Estimated rate of prostacyclin secretion into the circulation of normal man. J Clin Invest. 1981 Nov;68(5):1272–1276. doi: 10.1172/JCI110373. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FitzGerald G. A., Healy C., Daugherty J. Thromboxane A2 biosynthesis in human disease. Fed Proc. 1987 Jan;46(1):154–158. [PubMed] [Google Scholar]
- Fitzgerald D. J., Rocki W., Murray R., Mayo G., FitzGerald G. A. Thromboxane A2 synthesis in pregnancy-induced hypertension. Lancet. 1990 Mar 31;335(8692):751–754. doi: 10.1016/0140-6736(90)90869-7. [DOI] [PubMed] [Google Scholar]
- Granström E., Westlund P., Kumlin M., Nordenström A. Monitoring thromboxane production in vivo: metabolic and analytical aspects. Adv Prostaglandin Thromboxane Leukot Res. 1985;15:67–70. [PubMed] [Google Scholar]
- Gross S., Keefer V., Liebman J. The platelets in cyanotic congenital heart disease. Pediatrics. 1968 Oct;42(4):651–658. [PubMed] [Google Scholar]
- Hamberg M., Svensson J., Samuelsson B. Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci U S A. 1975 Aug;72(8):2994–2998. doi: 10.1073/pnas.72.8.2994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haworth S. G., Macartney F. J. Growth and development of pulmonary circulation in pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries. Br Heart J. 1980 Jul;44(1):14–24. doi: 10.1136/hrt.44.1.14. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ihenacho H. N., Fletcher D. J., Breeze G. R., Stuart J. Consumption coagulopathy in congenital heart-disease. Lancet. 1973 Feb 3;1(7797):231–234. doi: 10.1016/s0140-6736(73)90069-x. [DOI] [PubMed] [Google Scholar]
- Ingerman-Wojenski C., Silver M. J., Smith J. B., Macarak E. Bovine endothelial cells in culture produce thromboxane as well as prostacyclin. J Clin Invest. 1981 May;67(5):1292–1296. doi: 10.1172/JCI110157. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson R. J., Haworth S. G. Pulmonary vascular and alveolar development in tetralogy of Fallot: a recommendation for early correction. Thorax. 1982 Dec;37(12):893–901. doi: 10.1136/thx.37.12.893. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MacDermot J., Kelsey C. R., Waddell K. A., Richmond R., Knight R. K., Cole P. J., Dollery C. T., Landon D. N., Blair I. A. Synthesis of leukotriene B4, and prostanoids by human alveolar macrophages: analysis by gas chromatography/mass spectrometry. Prostaglandins. 1984 Feb;27(2):163–179. doi: 10.1016/0090-6980(84)90071-6. [DOI] [PubMed] [Google Scholar]
- Markelonis G., Garbus J. Alterations of intracellular oxidative metabolism as stimuli evoking prostaglandin biosynthesis. Prostaglandins. 1975 Dec;10(6):1087–1106. doi: 10.1016/s0090-6980(75)80056-6. [DOI] [PubMed] [Google Scholar]
- Maurer H. M. Hematologic effects of cardiac disease. Pediatr Clin North Am. 1972 Nov;19(4):1083–1093. doi: 10.1016/s0031-3955(16)32784-5. [DOI] [PubMed] [Google Scholar]
- Moncada S., Gryglewski R., Bunting S., Vane J. R. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature. 1976 Oct 21;263(5579):663–665. doi: 10.1038/263663a0. [DOI] [PubMed] [Google Scholar]
- Moncada S., Vane J. R. Arachidonic acid metabolites and the interactions between platelets and blood-vessel walls. N Engl J Med. 1979 May 17;300(20):1142–1147. doi: 10.1056/NEJM197905173002006. [DOI] [PubMed] [Google Scholar]
- Olson D. M., Tanswell A. K. Effects of oxygen, calcium ionophore, and arachidonic acid on prostaglandin production by monolayer cultures of mixed cells and endothelial cells from rat fetal lungs. Exp Lung Res. 1987;12(3):207–221. doi: 10.3109/01902148709064301. [DOI] [PubMed] [Google Scholar]
- Patrono C., Ciabattoni G., Pugliese F., Pierucci A., Blair I. A., FitzGerald G. A. Estimated rate of thromboxane secretion into the circulation of normal humans. J Clin Invest. 1986 Feb;77(2):590–594. doi: 10.1172/JCI112341. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rosenkranz B., Fischer C., Weimer K. E., Frölich J. C. Metabolism of prostacyclin and 6-keto-prostaglandin F1 alpha in man. J Biol Chem. 1980 Nov 10;255(21):10194–10198. [PubMed] [Google Scholar]
- Roszinski S., Jelkmann W. Effect of PO2 on prostaglandin E2 production in renal cell cultures. Respir Physiol. 1987 Nov;70(2):131–141. doi: 10.1016/0034-5687(87)90045-4. [DOI] [PubMed] [Google Scholar]
- Roy L., Knapp H. R., Robertson R. M., FitzGerald G. A. Endogenous biosynthesis of prostacyclin during cardiac catheterization and angiography in man. Circulation. 1985 Mar;71(3):434–440. doi: 10.1161/01.cir.71.3.434. [DOI] [PubMed] [Google Scholar]
- Rumsby G., Belloque J., Ersser R. S., Seakins J. W. Effect of temperature and sample preparation on performance of ion-moderated partition chromatography of organic acids in biological fluids. Clin Chim Acta. 1987 Mar 16;163(2):171–183. doi: 10.1016/0009-8981(87)90020-9. [DOI] [PubMed] [Google Scholar]
- Stuart M. J., Setty Y., Walenga R. W., Graeber J. E., Ganley C. Effects of hyperoxia and hypoxia on vascular prostacyclin formation in vitro. Pediatrics. 1984 Oct;74(4):548–553. [PubMed] [Google Scholar]
- Waldman J. D., Czapek E. E., Paul M. H., Schwartz A. D., Levin D. L., Schindler S. Shortened platelet survival in cyanotic heart disease. J Pediatr. 1975 Jul;87(1):77–79. doi: 10.1016/s0022-3476(75)80073-4. [DOI] [PubMed] [Google Scholar]
- Yeager S. B., Freed M. D. Myocardial infarction as a manifestation of polycythemia in cyanotic heart disease. Am J Cardiol. 1984 Mar 15;53(7):952–953. doi: 10.1016/0002-9149(84)90532-0. [DOI] [PubMed] [Google Scholar]