Pulmonary hypertension and arterial changes in calves with a systemic-to-left pulmonary artery connection

Abstract

The pathogenic mechanisms by which increased pressure and flow lead to pulmonary vascular disease are poorly understood, especially in newborns. To study the pathophysiological correlations and timing of the development of structural changes in response to high flow in nonhypoxic neonates, a model of high pulmonary flow was developed in newborn calves by anastomosis of the isolated left pulmonary artery (LPA) to the aorta. LPA pressure and flow increased acutely. LPA pressure reached near-systemic levels by 10 wk, whereas LPA flow was maximally increased at 1 mo before decreasing in several calves. Right pulmonary arterial pressure remained normal, and ventricular hypertrophy did not develop. Morphometric evaluation of the left lung demonstrated decreased arteriolar diameter, increased medial thickness, muscularization of arterioles at the bronchoalveolar junction, luminal obliteration of small arteries, and dilation lesions. The LPA pressure and vascular changes were greater and developed over a shorter time period than did prior models of nonhypoxic flow-induced pulmonary vascular changes. Lesser degrees of decreased arteriolar diameter and muscularization of small vessels were seen in the right lung, indicating a difference in the vascular response to moderately increased flow vs. increased pressure and flow. Thus, calves with an isolated LPA-to-aortic anastomosis simulate the hemodynamic and pulmonary vascular changes seen in newborns with congenital heart defects. Such calves may serve as models to assess effects of mechanical stresses on a newborn's vasculature.