Hemodynamic and histologic characterization of a swine (Sus scrofa domestica) model of chronic pulmonary arterial hypertension

Abstract

The purpose of this work was to develop and characterize an aortopulmonary shunt model of chronic pulmonary hypertension in swine and provide sequential hemodynamic, angiographic, and histologic data by using an experimental endoarterial biopsy catheter. Nine Yucatan female microswine (Sus scrofa domestica) underwent surgical anastomosis of the left pulmonary artery to the descending aorta. Sequential hemodynamic, angiographic, and pulmonary vascular samples were obtained. Six pigs (mean weight, 22.4±5.3 kg; mean age, 7.3±2.7 mo at surgery) survived long-term (6 mo) and consistently developed marked pulmonary arterial hypertension. Angiography showed characteristic central pulmonary arterial enlargement and peripheral tortuosity and pruning. The biopsy catheter was safe and effective in obtaining pulmonary endoarterial samples for histologic studies, which showed neointimal and medial changes. Autopsy confirmed severe pulmonary vascular changes, including concentric obstructive neointimal and plexiform-like lesions. This swine model showed hemodynamic, angiographic, and histologic characteristics of chronic pulmonary arterial hypertension that mimicked the arterial pulmonary hypertension of systemic-to-pulmonary arterial shunts in humans. Experimental data obtained using this and other models and application of an in vivo endoarterial biopsy technique may aid in understanding mechanisms and developing therapies for experimental and human pulmonary arterial hypertension.

Figure 1.

Schematic of normal anatomy and the aortopulmonary anastomosis. At surgery, the left pulmonary artery (LPA) was connected to the descending aorta. IVC, inferior vena cava; LA, left atrium; LV, left ventricle; RA, right ventricle; RPA, right pulmonary artery; RV, right ventricle; SVC, superior vena cava.

Figure 2.

Left pulmonary artery (LPA) systolic pressure (as a ratio of systemic systolic pressure) compared with time after surgical shunt creation in 6 micropigs that survived long-term.

Figure 3.

(A) Pulmonary arteriogram in a normal, nonhypertensive micropigs. (B) Left pulmonary artery angiograms after development of systemic level pulmonary arterial hypertension, showing proximal dilation, peripheral tortuosity, and marked pruning with loss of branching vessels.

Figure 4.

(A) Endoarterial biopsy samples obtained at baseline from presurgical, normal pulmonary artery. Hematoxylin and eosin stain; magnification, ×40. (B) Postsurgical left pulmonary artery with systemic pulmonary hypertension, showing thickened neointima (arrows) and disorganized medial layer. Hematoxylin and eosin stain; magnification, ×40. (C) Specimen of the left (hypertensive) lung at time of necropsy, showing vascular occlusive and plexiform-like lesions. Hematoxylin and eosin stain; magnification, ×10.

Figure 5.

Specimens of (A) right and (B) left lungs obtained at the time of necropsy. (A) The right pulmonary artery (normotensive lung) shows a smooth wall (arrows) with normal thickness. (B) The left pulmonary artery (hypertensive lung) shows considerable thickening of the wall (arrows) and a thrombus (T) partially occluding the lumen.