Circulation, Vol 87, 440-446, Copyright © 1993 by American Heart Association
DS Celermajer, S Cullen and JE Deanfield
BACKGROUND. Endothelial injury may be an important event in the
pathophysiology of pulmonary hypertension. We therefore investigated
whether endothelial dysfunction occurs early in children with congenital
heart defects who are at risk of developing pulmonary vascular disease.
METHODS AND RESULTS. In 25 children aged 3-16 years, we studied the
response of the pulmonary circulation to graded infusions of acetylcholine
(an endothelium-dependent vasodilator) and nitroprusside (a dilator not
dependent on endothelial function). Diameter of a bronchopulmonary segment
artery and pulmonary blood flow velocity were measured using quantitative
angiography and intra- arterial Doppler catheters in 10 children aged 4-16
years with normal pulmonary hemodynamics (controls), seven children aged
3-12 years with left-to-right shunt lesions resulting in increased
pulmonary flow, and eight children aged 3-14 years with established
pulmonary vascular disease. In the controls, there was a dose-dependent
increase in flow velocity in response to acetylcholine (maximal increase,
93 +/- 7%) and in response to nitroprusside (51 +/- 8%). In contrast, in
patients with pulmonary vascular disease, the response of flow velocity to
similar doses of acetylcholine (33 +/- 7%, p < 0.01) and nitroprusside
(7 +/- 13%, p < 0.01) were impaired. In the patients with high pulmonary
flow, there was an impaired response to acetylcholine (46 +/- 9%, p <
0.01), but response to nitroprusside was preserved (42 +/- 8%, p >
0.10), consistent with endothelial dysfunction. Arterial diameter was
unchanged during acetylcholine infusion in all subjects and increased only
modestly in response to nitroprusside (< or = 10%), indicating that the
major site of action of each agent is distal to the segmental pulmonary
arteries. CONCLUSIONS. Endothelium-dependent pulmonary artery relaxation
can be demonstrated in vivo and is impaired in young patients with
increased pulmonary flow secondary to congenital heart disease. This
impairment may be an important early event in the pathogenesis of pulmonary
vascular disease.
ARTICLES
Impairment of endothelium-dependent pulmonary artery relaxation in children with congenital heart disease and abnormal pulmonary hemodynamics
Cardiothoracic Unit, Hospital for Sick Children, London, UK.
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