The pulmonary vasculature in a neonatal porcine model with increased pulmonary blood flow and pressure

Introduction: Hypertension and hyperperfusion of the pulmonary vascular bed in the setting of congenital cardiac malformations may lead to progressive pulmonary vascular disease. To improve the understanding of the basic mech anisms of this disease, there is a need for clinically relevant animal mode ls which reflect the disease process, Material and Results: We randomly all ocated 45 newborn pips, at the age of 48 hrs, to groups in which there was either construction of a 3 mm central aorto-pulmonary shunt, undertaken in 9, or ligation of the left pulmonary artery, achieved in 13. Controls inclu ded sham operations in 13, or no operations in 10 pigs. Follow-up was conti nued for three months. The interventions were compatible with survival in m ost pigs. The shunts resulted in an acute 85% increase in systolic pulmonar y arterial pressure, and a more than twofold increase in pulmonary blood fl ow. By three months of age, nearly all shunts had closed spontaneously, and haemodynamics were normal. Ligation of the left pulmonary artery resulted in a normal total pulmonary blood flow, despite only the right lung being p erfused, and a 33% increase in systolic pulmonary arterial pressure. These haemodynamic changes were maintained throughout the period of study. In bot h groups, histomorphometry revealed markedly increased muscularity of the i ntra-acinar pulmonary arteries. Circulating levels of endothelin were norma l in the shunted animals, and elevated in those with ligation of the left p ulmonary artery. Conclusion: In neonatal porcine models of pulmonary vascul ar disease, created by construction of 3 mm central aorto-pulmonary shunts and ligation of one pulmonary artery, we observed histopathological changes of the pulmonary vasculature similar to early hypertensive pulmonary vascu lar disease in humans. Elevated circulating levels of endothelin were assoc iated with abnormal haemodynamics rather than abnormal pathology These find ings could be valuable for future studies on the pathogenesis of hypertensi ve pulmonary vascular disease associated with congenital cardiac malformati ons.