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


CONCLUSIONS
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.
de Vroomen
M
M
Department of Cardiology (C5-P), Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, Netherlands.
Lopes Cardozo
R H
RH
Steendijk
P
P
Frölich
M
M
Baan
J
J
van Bel
F
F
D000818:Animals; D000831:Animals, Newborn; D001158:Arteries; D001794:Blood Pressure; D002245:Carbon Dioxide / Q000097:blood; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000097:blood*; D006439:Hemodynamics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000209:etiology; D007231:Infant, Newborn; D007700:Kinetics; D010100:Oxygen / Q000097:blood; D011651:Pulmonary Artery / Q000503:physiopathology; D012127:Respiratory Distress Syndrome, Newborn / Q000150:complications*; D012756:Sheep; D014655:Vascular Resistance
D019332:Endothelin-1; D002245:Carbon Dioxide; D010100:Oxygen