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Systemic arteriovenous fistula leads to pulmonary artery remodeling and abnormal vasoreactivity in the fetal lamb

¹Maternité, ⁵Service d'Histo-Embryologie, Hôpital Necker-Enfants Malades, Assistance Publique, Hôpitaux de Paris, Université Paris 5, 75015 Paris; ⁶Service de Physiologie-Explorations Fonctionnelles, Centre Hospitalier Universitaire Cochin, Assistance Publique, Hôpitaux de Paris, Université Paris 5, 75014 Paris; ⁴Unité 408, Institut National de la Santé et de la Recherche Médicale, 75018 Paris; ²Département de chirurgie cardiaque pédiatrique, Hôpital Marie Lannelongue, 92350 Le Plessis Robinson, France; and ³Unit of Vascular Biology and Pharmacology, Institute of Child Health, London WC1N 1EH, United Kingdom

Submitted 30 October 2002 ; accepted in final form 14 May 2003

Several cases of systemic arteriovenous fistula diagnosed in the human fetus have been associated with the postnatal development of persistent pulmonary hypertension. The aim of this study was to determine the effects of a prenatally created systemic arteriovenous fistula on the structure and reactivity of the pulmonary circulation in the fetal lamb. A fistula between the jugular vein and carotid artery was created in fetal lambs at 119-124 days of gestation. At delivery (134-139 days), left pulmonary artery (LPA) pressure was increased in the fistula group (n = 12) compared with controls (n = 11, P < 0.01). The pulmonary vascular resistance was significantly higher in the fistula group (P < 0.05), whereas mean LPA blood flow was not statistically different between the two groups. Morphometric analysis of the pulmonary vascular bed revealed an increase in the number of peripheral muscular arteries, together with an increase in pulmonary arterial medial thickness in the fistula group. There was no difference in the relative number or size of intraacinar arteries. In vitro organ bath studies on pulmonary arterial rings showed impaired endothelium-dependent relaxation in the fistula group compared with controls. However, endothelial nitric oxide synthase protein expression was similar in both groups, whereas endothelium-independent relaxation to sodium nitroprusside was greater in the fistula group compared with controls. A systemic arteriovenous fistula leads to both structural and functional alteration of the pulmonary vasculature, which might lead to the development of persistent pulmonary hypertension after birth.

pulmonary circulation; prenatal; persistent pulmonary hypertension of the newborn; endothelium

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