A reliable rabbit model for hyperkinetic pulmonary hypertension.

Abstract

To study the mechanisms of vascular remodeling and increased vascular reactivity, a reliable, economic, easy, and stable animal model of hyperkinetic pulmonary hypertension is needed. The purpose of this study was to construct an animal model of hyperkinetic pulmonary arterial hypertension by chronic systemic-pulmonary shunt in young rabbits. Thoracotomy was performed through a midsternal incision in 1-month-old rabbits, and anastomosis between the left carotid artery and pulmonary artery trunk created a chronic left-to-right shunt. After 3 months, the shunted artery was checked by echocardiography. Systolic, diastolic, and mean pulmonary arterial pressures were measured by microcatheterization. The pathologic changes of small pulmonary arteries were observed after staining with hematoxylin and eosin. Thickness and area indices were calculated. High-flow pulmonary hypertension was successfully established in 24 rabbits 3 months after operation. Relative to a sham operation group, the systolic, diastolic, and mean pulmonary arterial pressures were obviously increased in the experimental group (P < .05). Histologic examination showed that the thickness of arterial wall increased, the lumen became narrowed, and thickness and area indices increased in small pulmonary arteries (P < .05). We constructed a model mimicking the aberrant hemodynamic state in children with congenital heart disease with increased pulmonary blood flow to produce early characteristic morphology of hyperkinetic pulmonary hypertension. This method may provide an economic, easy, and stable animal model to study the mechanisms of pulmonary vascular remodeling in hyperkinetic pulmonary hypertension.