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Influence of pulmonary blood pressure and flow on endothelin-1 production in humans
S Ishikawa1, T Miyauchi, H Ueno
1Department of Pediatric Cardiology, Fukuoka Children's Hospital, Japan.
Insights
Endothelin-1 (ET-1) production increases with pulmonary hypertension due to pressure overload but decreases with volume overload in children with congenital heart disease.
Area of Science:
- Cardiology
- Pediatric Cardiology
- Vascular Biology
Background:
- Endothelin-1 (ET-1) plays a crucial role in cardiovascular regulation.
- Understanding ET-1 production in congenital heart disease (CHD) is vital for managing pulmonary circulation.
- Altered hemodynamics in CHD can impact ET-1 levels.
Purpose of the Study:
- To investigate the regulation of endothelin-1 (ET-1) production in pediatric patients with congenital heart disease.
- To determine how different hemodynamic loads (pressure vs. volume overload) affect ET-1 levels.
- To assess the influence of pulmonary hypertension and congestion on ET-1.
Main Methods:
- Cardiac catheterization in young patients with CHD (mean age 27 months).
- Measurement of plasma ET-1 levels in the inferior vena cava using sandwich-enzyme immunoassay.
- Comparison of ET-1 levels between patient groups (atrial septal defect, ventricular septal defect with PH, pulmonary venous stenosis with PH) and healthy controls.
Main Results:
- Patients with atrial septal defect (volume overload, no PH) showed significantly lower ET-1 levels than controls.
- Patients with ventricular septal defect (VSD) and PH (pressure & volume overload) had significantly higher ET-1 levels.
- Patients with PH and severe pulmonary congestion due to pulmonary venous stenosis (PVS) exhibited even higher ET-1 levels than VSD patients, suggesting ET-1 augmentation by congestion.
Conclusions:
- ET-1 production is increased by pressure overload to the pulmonary circulation in pediatric CHD.
- ET-1 production is decreased by volume overload to the pulmonary circulation.
- Pulmonary congestion may further augment ET-1 production in patients with severe CHD.
Abstract:
To investigate the regulation of endothelin-1 (ET-1) production, cardiac catheterization was performed in young patients with congenital heart disease (27 +/- 5 months old, mean +/- SEM), and plasma levels of ET-1 in the inferior vena cava were measured by a sandwich-enzyme immunoassay. Plasma ET-1 levels of age-matched healthy controls were 1.55 +/- 0.07 pg/ml (n = 6). In patients with atrial septal defect [without pulmonary hypertension (PH)] who had volume but not pressure overload to the pulmonary circulation (PC), plasma ET-1 levels were significantly lower than in controls. In patients with PH due to ventricular septal defect (VSD) who had both volume and pressure overload to PC, the levels were significantly higher than in controls. In patients with PH and severe pulmonary congestion due to pulmonary venous stenosis (PVS), plasma ET-1 levels were significantly higher than in those with VSD, suggesting that ET-1 production is also augmented by pulmonary congestion. The present findings suggest that ET-1 production is increased by pressure overload to PC but decreased by volume overload to PC.