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J Thorac Cardiovasc Surg 1995;110:271-273
© 1995 Mosby, Inc.
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Fukuoka, Osaka, and Ibaraki, Japan
Supported by grants from the Special Research Project on the Circulation Biosystem in the University of Tsukuba, the Study Group of Molecular Cardiology, and Clinical Research in Fukuoka Children's Hospital.
Congenital heart diseases (CHD) are often accompanied by pulmonary hypertension (PH), and the severity of PH is an important determinant of the prognosis of such patients. 
1 Endothelin-1 (ET-1), an endothelium-derived peptide, has potent contractile and proliferative effects on vascular smooth muscle cells. 2, 3 Elevated plasma concentration of ET-1 has been reported in patients with PH of both primary and secondary forms. 4 Yoshibayashi, 5 Vincent, 6 and their associates have reported that plasma ET-1 levels are elevated in patients with PH caused by CHD. Elevated plasma ET-1 concentrations have also been reported in rats with experimentally induced PH, and an endothelin receptor antagonist effectively attenuated the development of PH in the rats. 7 These observations suggest that endogenous ET-1 may have an important role in the increased pulmonary vascular tonus or medial hypertrophy of the pulmonary blood vessels in patients with PH. However, no information is available regarding whether elevated plasma ET-1 is altered by amelioration of clinical status of PH. The aim of the present study is to investigate whether elevated plasma ET-1 in young patients with PH caused by CHD changes after surgical repair for CHD.
Eleven patients with PH caused by CHD were studied. Their ages were 6.7 ± 1.2 (mean ± standard error of the mean) months at operation. Their diagnoses were ventricular septal defect in six patients, total anomalous pulmonary venous drainage in two, cor triatriatum in one, and pulmonary venous stenosis after repair of total anomalous pulmonary venous drainage in two. Informed consent was obtained from the parents of each patient enrolled for the study. On all the patients, surgical repair (total correction) was successful. Before and 4 weeks after the operation, percutaneous cardiac catheterization via the femoral vein was performed with routine sedation. Six patients with anatomically normal hearts and normal hemodynamics without PH served as controls; their ages were 11.0 ± 2.5 months. The blood samples (4 ml of whole blood) were obtained from the inferior vena cava for analysis of plasma ET-1 levels. The samples were placed into chilled tubes containing sodium ethylenediaminetetraacetate and aprotinin. Plasma ET-1 levels were measured by a sandwich-enzyme immunoassay as previously described. 8, 9 Data were expressed as mean ± standard error of the mean. The significance of difference was analyzed by paired/unpaired Student's t test. A P value less than 0.05 was considered statistically significant.
In all the patients with PH, surgical repair for CHD was performed successfully, and the hemodynamic states of the pulmonary circulation 4 weeks after the operation were greatly improved; that is, the operation significantly decreased systolic pulmonary blood pressure (738 ± 4.7 mm Hg to 39.0 ± 4.7 mm Hg, n = 11, p < 0.001), total pulmonary vascular resistance index (12.2 ± 0.3 unit x m2 to 5.6 ± 1.2 unit x m2 , n = 11, p < 0.05), and mean pulmonary arterial wedge pressure (17.0 ± 2.8 mm Hg to 8.0 ± 1.2 mm Hg, n = 11, p < 0.001). On the other hand, neither systolic systemic blood pressure nor systemic vascular resistance was affected by the operation. These observations suggested that surgical repair markedly ameliorated PH, pulmonary congestion, and complications that affected all the patients before the operation. Preoperative plasma ET-1 levels of the patients with PH were significantly higher than those of age-matched control subjects (3.96 ± 0.53 pg/ml, n = 11, versus 1.63 ± 0.13 pg/ml, n = 6, p < 0.001, Fig. 1). The elevated ET-1 levels were markedly reduced 4 weeks after the operation (3.96 ± 0.53 pg/ml to 1.98 ± 0.14 pg/ml, n = 11, p < 0.001, Fig. 1).
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5 have indicated a significant step-up in plasma ET-1 concentrations in the pulmonary vein when compared with those in the right ventricle, and they suggested that ET-1 is released from the pulmonary circulation. It has also been demonstrated that expression of ET-1 increased in the pulmonary vascular endothelial cells of patients with PH. 10 Thus the increase in ET-1 production in pulmonary circulation may be reflected, at least in part, on an increase in plasma ET-1 in patients with PH. Taken together, these observations seem to indicate that the pressure overload may injure the pulmonary vascular endothelial cells and hence lead to an elevation of ET-1 production in the patients with PH. Furthermore, the excessively produced ET-1 may aggravate the pulmonary hemodynamics through its potent and long-lasting vasoconstrictive as well as proliferative actions on the pulmonary artery. After surgery, in turn, these pathophysiologic conditions of pulmonary circulation may be ameliorated in a reverse direction.
The present findings suggest that the extent of increase in plasma ET-1 levels in patients with PH may reflect the abnormalities of pulmonary circulation. Because electron microscopic study has demonstrated that the pulmonary artery endothelial cells are injured in patients with PH caused by CHD, 11 it is likely that a successful operation might ameliorate endothelial injuries, thereby reducing the elevated production of ET-1 in pulmonary vascular endothelial cells. We consider, therefore, that the improved conditions of pulmonary vascular endothelial cells may play an important role in ameliorating the clinical symptoms in the patients with PH caused by CHD after successful operations.
Footnotes
From the Departments of Pediatric Cardiologya and Cardiac Surgery,b Fukuoka Children's Hospital, 2-5-1 Tohjin-machi, Chuo-ku, Fukuoka 810, Japan; the Takeda Analytical Research Laboratory,c Osaka, Japan; and the Departments of Internal Medicined andPharmacology,e University of Tsukuba, Ibaraki, Japan. 
J THORAC CARDIOVASC SURG 1995;110:271-3
References
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