Skip to main content
NCBI home page
British Heart Journal logoLink to British Heart Journal
. 1994 Nov;72(5):452–456. doi: 10.1136/hrt.72.5.452

Effect of intracardiac repair on biosynthesis of thromboxane A2 and prostacyclin in children with a left to right shunt.

I Adatia 1, S E Barrow 1, P D Stratton 1, J M Ritter 1, S G Haworth 1
PMCID: PMC1025613  PMID: 7818962

Abstract

OBJECTIVE--To investigate the effect of intracardiac repair on the abnormal biosynthesis of prostacyclin (PGI2) and thromboxane A2 (TXA2) in children with congenital heart disease and increased pulmonary blood flow. DESIGN--A prospective study with immunoaffinity chromatography and gas chromatography-mass spectrometry to measure the urinary excretion products of PGI2 (2,3-dinor-6-oxo-prostaglandin (PG) F1 alpha (2,3-dinor-6-oxo-PGF1 alpha)) and TXA2 (2,3-dinor-TXB2) before operation, in the first 12-24 h after operation, and at discharge from hospital. SETTING--A supraregional referral centre for patients with congenital heart disease. PATIENTS--15 patients aged 2 to 60 months (median 7 months) with a left to right shunt who underwent intracardiac repair. RESULTS--The preoperative 2,3-dinor-TXB2 excretion rate was greater than that found previously in a control group of 16 healthy children with a median (range) age of 24 (6-36) months (1159(201) v 592(122) ng/g creatinine in controls, P = 0.006). The excretion rate rose after operation to 9600(3832) ng/g creatinine (P = 0.01) and decreased before discharge to 1071(191) ng/g creatinine (NS), but remained greater than that of the control group (P = 0.014). Before operation 2,3-dinor-6-oxo-PGF1 alpha excretion rates were similar to those of the healthy children (482(68) v 589(95) ng/g creatinine in controls) but increased after operation to 19,668(11,162) ng/creatinine (P = 0.002) and fell at discharge to 1621(245) ng/g creatinine although this was higher than both preoperative and control rates (P = 0.005 and P = 0.0002 respectively). The preoperative ratio of 2,3-dinor-TXB2 to 2,3-dinor-6-oxo-PGF1 alpha excretion was greater than that of the control group (3.2(0.8) v 1.3(0.22) in controls, (P = 0.005)), decreased significantly after operation to 0.9(0.13) (P = 0.016), and changed little, to 0.7(0.12), before discharge. The last two ratios were similar to those in normal children and significantly lower than those before operation (P = 0.004). CONCLUSION--In children with a left to right shunt the ratio of the excretion rates of the metabolites of TXA2 and PGI2 was abnormal before operation, which favoured vasoconstriction and platelet aggregation, but had decreased at discharge from hospital. The increase in excretion of PGI2 metabolites over TXA2 metabolite after intracardiac repair augurs well for pulmonary vascular recovery.

Full text

PDF
452

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adatia I., Barrow S. E., Stratton P. D., Miall-Allen V. M., Ritter J. M., Haworth S. G. Thromboxane A2 and prostacyclin biosynthesis in children and adolescents with pulmonary vascular disease. Circulation. 1993 Nov;88(5 Pt 1):2117–2122. doi: 10.1161/01.cir.88.5.2117. [DOI] [PubMed] [Google Scholar]
  2. Adatia I., Haworth S. G. Circulating endothelin in children with congenital heart disease. Br Heart J. 1993 Mar;69(3):233–236. doi: 10.1136/hrt.69.3.233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ando J., Komatsuda T., Kamiya A. Cytoplasmic calcium response to fluid shear stress in cultured vascular endothelial cells. In Vitro Cell Dev Biol. 1988 Sep;24(9):871–877. doi: 10.1007/BF02623896. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. Celermajer D. S., Cullen S., Deanfield J. E. Impairment of endothelium-dependent pulmonary artery relaxation in children with congenital heart disease and abnormal pulmonary hemodynamics. Circulation. 1993 Feb;87(2):440–446. doi: 10.1161/01.cir.87.2.440. [DOI] [PubMed] [Google Scholar]
  7. Chenoweth D. E., Cooper S. W., Hugli T. E., Stewart R. W., Blackstone E. H., Kirklin J. W. Complement activation during cardiopulmonary bypass: evidence for generation of C3a and C5a anaphylatoxins. N Engl J Med. 1981 Feb 26;304(9):497–503. doi: 10.1056/NEJM198102263040901. [DOI] [PubMed] [Google Scholar]
  8. Christman B. W., McPherson C. D., Newman J. H., King G. A., Bernard G. R., Groves B. M., Loyd J. E. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med. 1992 Jul 9;327(2):70–75. doi: 10.1056/NEJM199207093270202. [DOI] [PubMed] [Google Scholar]
  9. Faichney A., Davidson K. G., Wheatley D. J., Davidson J. F., Walker I. D. Prostacyclin in cardiopulmonary bypass operations. J Thorac Cardiovasc Surg. 1982 Oct;84(4):601–608. [PubMed] [Google Scholar]
  10. FitzGerald G. A., Healy C., Daugherty J. Thromboxane A2 biosynthesis in human disease. Fed Proc. 1987 Jan;46(1):154–158. [PubMed] [Google Scholar]
  11. Fitzgerald D. J., Entman S. S., Mulloy K., FitzGerald G. A. Decreased prostacyclin biosynthesis preceding the clinical manifestation of pregnancy-induced hypertension. Circulation. 1987 May;75(5):956–963. doi: 10.1161/01.cir.75.5.956. [DOI] [PubMed] [Google Scholar]
  12. Fleming W. H., Sarafian L. B., Leuschen M. P., Newland M. C., Kennedy E. M., Kugler J. D., Chapin J. W., Hurlbert B. J., Bolam D. L., Nelson R. M., Jr Serum concentrations of prostacyclin and thromboxane in children before, during, and after cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1986 Jul;92(1):73–78. [PubMed] [Google Scholar]
  13. Greeley W. J., Bushman G. A., Kong D. L., Oldham H. N., Peterson M. B. Effects of cardiopulmonary bypass on eicosanoid metabolism during pediatric cardiovascular surgery. J Thorac Cardiovasc Surg. 1988 May;95(5):842–849. [PubMed] [Google Scholar]
  14. Hall S. M., Haworth S. G. Onset and evolution of pulmonary vascular disease in young children: abnormal postnatal remodelling studied in lung biopsies. J Pathol. 1992 Feb;166(2):183–193. doi: 10.1002/path.1711660216. [DOI] [PubMed] [Google Scholar]
  15. Hamberg M., Samuelsson B. Prostaglandin endoperoxides. Novel transformations of arachidonic acid in human platelets. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3400–3404. doi: 10.1073/pnas.71.9.3400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Higgs E. A., Moncada S., Vane J. R., Caen J. P., Michel H., Tobelem G. Effect of prostacyclin (PGI2) on platelet adhesion to rabbit arterial subendothelium. Prostaglandins. 1978 Jul;16(1):17–22. doi: 10.1016/0090-6980(78)90197-1. [DOI] [PubMed] [Google Scholar]
  18. Kirklin J. K. Prospects for understanding and eliminating the deleterious effects of cardiopulmonary bypass. Ann Thorac Surg. 1991 Apr;51(4):529–531. doi: 10.1016/0003-4975(91)90302-7. [DOI] [PubMed] [Google Scholar]
  19. Kirklin J. K., Westaby S., Blackstone E. H., Kirklin J. W., Chenoweth D. E., Pacifico A. D. Complement and the damaging effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1983 Dec;86(6):845–857. [PubMed] [Google Scholar]
  20. Komai H., Adatia I. T., Elliott M. J., de Leval M. R., Haworth S. G. Increased plasma levels of endothelin-1 after cardiopulmonary bypass in patients with pulmonary hypertension and congenital heart disease. J Thorac Cardiovasc Surg. 1993 Sep;106(3):473–478. [PubMed] [Google Scholar]
  21. Longmore D. B., Bennett J. G., Hoyle P. M., Smith M. A., Gregory A., Osivand T., Jones W. A. Prostacyclin administration during cardiopulmonary bypass in man. Lancet. 1981 Apr 11;1(8224):800–804. doi: 10.1016/s0140-6736(81)92680-5. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Patrono C., Ciabattoni G., Patrignani P., Filabozzi P., Pinca E., Satta M. A., van Dorne D., Cinotti G. A., Pugliese F., Pierucci A. Evidence for a renal origin of urinary thromboxane B2 in health and disease. Adv Prostaglandin Thromboxane Leukot Res. 1983;11:493–498. [PubMed] [Google Scholar]
  24. Patrono C., Pugliese F., Ciabattoni G., Patrignani P., Maseri A., Chierchia S., Peskar B. A., Cinotti G. A., Simonetti B. M., Pierucci A. Evidence for a direct stimulatory effect of prostacyclin on renin release in man. J Clin Invest. 1982 Jan;69(1):231–239. doi: 10.1172/JCI110435. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Rabinovitch M., Bothwell T., Hayakawa B. N., Williams W. G., Trusler G. A., Rowe R. D., Olley P. M., Cutz E. Pulmonary artery endothelial abnormalities in patients with congenital heart defects and pulmonary hypertension. A correlation of light with scanning electron microscopy and transmission electron microscopy. Lab Invest. 1986 Dec;55(6):632–653. [PubMed] [Google Scholar]
  26. Ratliff N. B., Young W. G., Jr, Hackel D. B., Mikat E., Wilson J. W. Pulmonary injury secondary to extracorporeal circulation. An ultrastructural study. J Thorac Cardiovasc Surg. 1973 Mar;65(3):425–432. [PubMed] [Google Scholar]
  27. Ritter J. M., Hamilton G., Barrow S. E., Heavey D. J., Hickling N. E., Taylor K. M., Hobbs K. E., Dollery C. T. Prostacyclin in the circulation of patients with vascular disorders undergoing surgery. Clin Sci (Lond) 1986 Dec;71(6):743–747. doi: 10.1042/cs0710743. [DOI] [PubMed] [Google Scholar]
  28. Rosenthal J. E., Ferrier G. R. Contribution of variable entrance and exit block in protected foci to arrhythmogenesis in isolated ventricular tissues. Circulation. 1983 Jan;67(1):1–8. doi: 10.1161/01.cir.67.1.1. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. 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]
  31. Schranz D., Zepp F., Iversen S., Wippermann C., Huth R., Zimmer B., Jüngst B. K., Oelert H. Effects of tolazoline and prostacyclin on pulmonary hypertension in infants after cardiac surgery. Crit Care Med. 1992 Sep;20(9):1243–1249. [PubMed] [Google Scholar]
  32. Smith W. J., Murphy M. P., Appleyard R. F., Rizzo R. J., Aklog L., Laurence R. G., Cohn L. H. Prevention of complement-induced pulmonary hypertension and improvement of right ventricular function by selective thromboxane receptor antagonism. J Thorac Cardiovasc Surg. 1994 Mar;107(3):800–806. [PubMed] [Google Scholar]
  33. Wessel D. L., Adatia I., Giglia T. M., Thompson J. E., Kulik T. J. Use of inhaled nitric oxide and acetylcholine in the evaluation of pulmonary hypertension and endothelial function after cardiopulmonary bypass. Circulation. 1993 Nov;88(5 Pt 1):2128–2138. doi: 10.1161/01.cir.88.5.2128. [DOI] [PubMed] [Google Scholar]
  34. van Oeveren W., Harder M. P., Roozendaal K. J., Eijsman L., Wildevuur C. R. Aprotinin protects platelets against the initial effect of cardiopulmonary bypass. J Thorac Cardiovasc Surg. 1990 May;99(5):788–797. [PubMed] [Google Scholar]

Articles from British Heart Journal are provided here courtesy of BMJ Publishing Group

RESOURCES