endothelin-1 and Heart-Septal-Defects--Ventricular

Haemodynamic disturbances due to ventricular septal defect (VSD) can lead to heart failure (HF) and cause neurohormonal activation. Endothelin-1 (ET-1) clearance takes place mainly in the pulmonary circulation. We hypothesized that increased pulmonary blood flow in children with VSD could influence ET-1 level and reflect haemodynamic disturbances in these patients.. To analyse usefulness of plasma ET-1 level in the evaluation of HF severity in infants with VSD without pulmonary hypertension.. The study group included 34 children (aged 38-338 days, mean 130 ± 81 days) with VSD. Evaluation included history, physical examination, ET-1 level measurement, standard 12-lead electrocardiogram, chest X-ray, and transthoracic echocardiography in all children. The control group consisted of 31 healthy children.. Mean plasma ET-1 level was significantly (p < 0.01) higher in the study group compared to the control group. We found no significant difference (p > 0.05) in mean plasma ET-1 level between children with or without HF. No significant correlation was found between plasma ET-1 level and the severity of HF.. Infants with VSD show higher ET-1 level compared to healthy children. Plasma ET-1 level does not reflect the severity of HF in infants with VSD.

Topics: Child, Preschool; Echocardiography; Endothelin-1; Female; Heart Septal Defects, Ventricular; Hemodynamics; Humans; Infant; Male; Severity of Illness Index

Children with Down's syndrome (DS)-associated complete atrioventricular septal defect (AVSD) have rapid and aggressive development of pulmonary vascular disease when compared with non-Down's syndrome (ND) children. We aimed to evaluate the role of plasma endothelin-1 (ET-1) and nitrate levels in DS children with complete AVSD-associated pulmonary hypertension (PH) and compare this to ND patients. The study included 20 patients (11 males, nine females) who had complete AVSD associated with PH. Comparisons were made between DS patients (n=12) aged 4 to 8 months (median 5 months) and ND patients (n=8) aged 4 to 12 months (median 7 months). Blood samples were drawn from the inferior vena cava, pulmonary artery, pulmonary vein, and aorta. The plasma ET-1 concentrations of the two groups were compared to the peripheral venous and arterial ET-1 levels, and pulmonary vein nitrate was compared to the peripheral arterial nitrate levels of ten healthy infants. The mean pulmonary artery (PA) pressure and pulmonary vascular resistance (Rp) were significantly higher in the DS group than ND patients, and the pulmonary blood flow (Qp) in ND patients was higher than DS patients. There were no differences between the two study groups in regard to plasma ET-1 and nitrate levels obtained from matched sampling sites. The plasma ET-1 and nitrate levels were significantly higher in both study groups compared to the control subjects. The plasma ET-1 and nitrate levels in DS patients with PH were not different when compared to those of ND patients.

Topics: Child; Child, Preschool; Down Syndrome; Endothelin-1; Female; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Humans; Hypertension, Pulmonary; Male; Nitrates

A 4-month-old female with ventricular septal defect (VSD) and severe pulmonary hypertension (PH) underwent a patch closure for VSD. She could not be weaned from cardiopulmonary bypass (CPB) after the intracardiac repair due to PH crisis. Nitric oxide inhalation therapy during partial CPB enabled her to be weaned from CPB. This therapy could be gradually taped off and quit 7 days after the operation. Nitric oxide inhaled therapy is considered to be an excellent treatment for PH crisis during CPB in congenital cardiac surgery. The causes of PH crisis were also discussed in reference to the date of endothelin-1 (ET-1) measured during the operation.

Topics: Administration, Inhalation; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Endothelin-1; Female; Heart Septal Defects, Ventricular; Humans; Hypertension, Pulmonary; Infant; Nitric Oxide

The changes of adrenomedullin (ADM), endothelin-1 (ET-1) and nitric oxide (NO) levels before and after operation in congenital heart disease (CHD) associated with pulmonary hypertension (PH) were observed in order to investigate their role in CHD with PH and their clinical significance. The CHD patients were divided into 3 groups according to pulmonary artery systolic pressure (PASP): Non-PH group: PASP < or = 30 mmHg (n = 11); mild-PH group: PASP 31-49 mmHg (n = 10); moderate or severe-PH group: PASP > or = 50 mmHg (n = 12). The control group consisted of 15 health children. Plasma ADM, ET-1 and NO levels were determined by radioimmunoassay and colorimetry methods. The correlation between ADM and ET-1, NO, PASP was analyzed. The changes in plasma ADM, ET-1 and plasma NO on the 7th day after operation among the groups were compared. The results showed that plasma ADM levels in non-PH group were significantly higher than that in control group (P < 0.05), but there was no significant difference in ET-1 and NO levels between the two groups (P > 0.05). ADM and ET-1 levels in mild-PH group were significantly elevated as compared with those in non-PH group (both P < 0.05), but NO levels were decreased (P < 0.05). ADM and ET-1 levels in moderate or severe-PH groups were increased as compared with those in mild-PH group (both P < 0.01), but NO level significantly declined (P < 0.05). On the 7th day after operation, plasma ADM and ET-1 levels in PH group were significantly decreased (P < 0.05, P < 0.01) as compared with those before operation, but there was no significant difference in NO levels (P > 0.05). But NO levels in non-PH group were significantly increased (P < 0.05). Plasma ADM levels in CHD were positively correlated with PASP and ET-1 (r = 0.77, P < 0.01; r = 0.82, P < 0.01), negatively correlated with NO (r = -0.56, P < 0.05). It was concluded that during the progression of PH in the cases of CHD, plasma ADM, ET-1 and NO might play an important role in the development of PH. The increased ADM may represent a compensatory mechanism. It can interact with NO and ET-1 to regulate pulmonary circulation in the pathophysiology of PH with CHD. ADM may be involved in the defence mechanism against further increase of pulmonary arterial pressure. ADM could be used as a reliable indicator of the severity of CHD associated PH.

Topics: Adolescent; Adrenomedullin; Child; Child, Preschool; Endothelin-1; Female; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Humans; Hypertension, Pulmonary; Infant; Male; Nitric Oxide; Peptides; Postoperative Period

Genetic disruption of endothelin (ET) 1, endothelin-converting enzyme (ECE) 1, and endothelin receptor A (ET(A)) in "knockout" or mutant mouse models result in defects in branchial arch derived craniofacial tissues and in cardiac outflow and great vessel structures. Interestingly, certain types of human congenital cardiovascular malformations such as Catch 22 syndrome and type B interruption of the aortic arch strongly resemble defects seen in knockout animal models. To better address the exact involvement of the ET system in heart formation we explored the spatiotemporal pattern of expression of the components of the ET system during critical phases of cardiogenesis in the human embryo (3-6 weeks of development; Carnegie stages 10-17) by in situ hybridization. We detected high ET-1 mRNA expression in endocardial cells lining the heart outflow tract in the region where the future aortic valves will form. No hybridization signal corresponding to pre-pro-ET-3 was observed in the heart. At the same location, the underlying myocytes express ET(A) mRNA. Whereas a functional role of ET in the valve formation can be proposed because of the simultaneous presence of all the components of the endothelin system (ET-1/ECE-1/ET(A)), this seems not to be the case for the formation of the ventricular septum where endocardial cells do not express ET-1, and only a weak ET(A) hybridization signal was detected in the surrounding myocardium. An abnormal hemodynamism indirectly due to valve malformation may be the indirect cause of this septal defect. The results of this study suggest an important role for the ET system in the formation of certain anatomical structures of the developing human heart.

Topics: Aorta, Thoracic; Aspartic Acid Endopeptidases; Endothelin-1; Endothelin-2; Endothelin-Converting Enzymes; Female; Fetal Heart; Gene Expression Regulation, Developmental; Gene Expression Regulation, Enzymologic; Heart Defects, Congenital; Heart Septal Defects, Ventricular; Humans; In Situ Hybridization; In Vitro Techniques; Metalloendopeptidases; RNA, Messenger

To investigate the changes in plasma endothelin-1 (ET-1) concentrations in patients with congenital heart defects.. Plasma ET-1 concentrations were measured by using radio-immunoassay in 50 patients in a prospective study. In 35 patients with ventricular septal defect, 20 cases had pulmonary hypertension (group 1) and 15 cases had normal pulmonary artery pressure (group 2). The other 15 patients with atrial septal defect had normal pulmonary artery pressure (group 3). Blood samples were obtained from pulmonary artery, aorta and radial artery.. Plasma ET-1 concentration in group 1 was significantly higher than those in group 2 and group 3 at all sampling sites and all different times (p < 0.01), and plasma ET-1 concentration was slightly higher in group 3 than in group 2 (p > 0.05). Plasma ET-1 concentration at aorta were also significantly higher than that at pulmonary artery in group 1 (p < 0.01). In patients with ventricular septal detect, pulmonary blood flow had a linear positive correlation with plasma ET-1 concentration (r = 0.75, p < 0.01) and there was also a significant positive correlation between plasma ET-1 concentration and pulmonary artery pressure (r = 0.68, p < 0.05). After surgical repair of the defects, plasma ET-1 concentration decreased except for 6 cases with the pulmonary resistance more than 800 dyne.sec.cm-5.. Plasma ET-1 concentrations are elevated in patients with congenital heart defect associated with left-to-right shunt and may have an important role in the pathogenesis of pulmonary hypertension.

Topics: Child; Child, Preschool; Data Interpretation, Statistical; Endothelin-1; Female; Heart Defects, Congenital; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Humans; Hypertension, Pulmonary; Infant; Male; Prospective Studies; Radioimmunoassay