Abnormalities in the biosynthesis of thromboxane A2 and prostacyclin in children with cyanotic congenital heart disease.
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).


CONCLUSIONS
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.
Adatia
I
I
Department of Developmental Vascular Biology and Pharmacology, Institute of Child Health, London.
Barrow
S E
SE
Stratton
P
P
Ritter
J M
JM
Haworth
S G
SG
D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives / Q000652:urine; D002675:Child, Preschool; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006330:Heart Defects, Congenital / Q000378:metabolism* / Q000652:urine; D006801:Humans; D007223:Infant; D008297:Male; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine; D014694:Ventricular Outflow Obstruction / Q000378:metabolism* / Q000652:urine
D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C028965:2,3-dinor-thromboxane B2; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; D011464:Epoprostenol