Intrauterine pulmonary vascular disease is unusual, and the disease generally starts at birth.12 The rate of change depends on the type of intracardiac abnormality, but some exceptional children appear to be genetically predisposed to develop an accelerated form of the disease. Endothelial cell damage, medial smooth muscle cell hyperplasia, hypertrophy, and site specific changes in cell phenotype are well described in early infancy12 (fig 22.2). Respiratory unit arteries, about half of which normally form after birth, are reduced in size and number. This is the morphological substrate of pulmonary hypertensive crises, which most often occur in the presence of potentially reversible structural abnormalities. Endothelial dysfunction is present early. In potentially operable children the relaxation response to acetylcholine is impaired, basal NO production may be raised initially but then decreases, and the ratio of thromboxane to prostacyclin is raised, tipping the balance in favour of vasoconstriction and platelet aggregation. Impaired endothelial dependant relaxation occurs later in association with elevation in resistance and more advanced structural disease (fig 22.3). Dilatation and plexiform lesions contain abundant vascular endothelial growth factor (VEGF)
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