Endothelin-1 plasma concentration increases in the early phase of pulmonary hypertension development during respiratory distress syndrome: a study in newborn lambs

• Published in: Early human development 2001-06, Vol.63 (1), p.9-21
• Main Authors: de Vroomen, Maartje, Lopes Cardozo, Robbert H, Steendijk, Paul, Frölich, Marijke, Baan, Jan, van Bel, Frank
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Arteries; Biological and medical sciences; Blood Pressure; Carbon Dioxide - blood; Disease Models, Animal; Endothelin-1 - blood; Endothelins; Hemodynamics; Humans; Hydrogen-Ion Concentration; Hypertension, Pulmonary - blood; Hypertension, Pulmonary - etiology; Infant, Newborn; Kinetics; Medical sciences; Oxygen - blood; Pneumology; Pulmonary Artery - physiopathology; Pulmonary circulation; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Respiratory Distress Syndrome, Newborn - complications; Sheep; Vascular Resistance; Vasoconstriction/dilation
• ISSN: 0378-3782; 1872-6232
• DOI: 10.1016/S0378-3782(01)00143-8

Objective: Elevated plasma concentrations of endothelin-1 (ET-1) have been reported with pulmonary hypertension during respiratory distress syndrome (RDS). However, the exact role of ET-1 in the development of pulmonary hypertension during RDS is unclear. The relative time-course of changes in ET-1 concentrations and pulmonary artery pressure (P ap) during RDS may give insight in the role of ET-1. Methods: ET-1 and P ap changes were studied in an experimental model of RDS, induced by lung lavages in seven newborn lambs. Five other lambs served as controls. Results: Lung lavages induced a twofold increase of mean P ap (from 15 to 34 mm Hg) that remained present throughout the 4-h study period. Along with the increased P ap, ET-1 plasma concentration showed a significant increase 15 min after induction of RDS at all three sample locations (pulmonary artery 198%, aorta 181% and right atrium 195% compared to baseline). This increased concentration remained high at 1 and 4 h of RDS. In control animals, no significant changes in ET-1 concentrations were observed. Plotting ET-1 concentration values against mean P ap, in RDS and control animals at all time points, a correlation was found between the severity of the pulmonary hypertension and ET-1 concentration. Conclusion: This experimental model of RDS shows that ET-1 concentration increases concomitant with the development of pulmonary hypertension, from an early time point onward. More severe pulmonary hypertension is associated with higher ET-1 concentrations, but whether ET-1 is a marker or a mediator of pulmonary hypertension remains as yet unsettled.