Original rat model of high kinetic unilateral pulmonary hypertension surgically induced by combined surgery

Abstract

Objectives: The characteristic morphologic lesions observed in the lungs of patients with congenital cardiac anomalies have not been closely modeled in rat shunt-related models, except for the reversible grade 1 changes. The present study reported an original rat model of unilateral pulmonary hypertension surgically induced by combined surgery to reproduce more advanced pulmonary vascular lesions.

Methods: The right pulmonary artery was ligated through a right posterolateral thoracotomy, and a cervical shunt was established 1 week later. The immediate and chronic effects on the pulmonary hemodynamics were evaluated through right heart catheterization immediately after and at 8 and 12 weeks postoperatively. The morphologic changes in pulmonary vasculature were analyzed after staining with hematoxylin-eosin and modified Weigert's method. The right ventricular hypertrophy index was calculated and artery blood gas analysis performed.

Results: A pulmonary hypertensive status was successfully induced immediately after cervical surgery and progressively aggravated into a borderline state with disease course advancing. Pulmonary vasculopathy demonstrated a transition from reversibility (muscularization, intimal proliferation of grade 1-2) at 8 weeks to irreversibility (intimal fibrosis, entirely luminal occlusion, grade 3) at 12 weeks postoperatively. Conspicuous right ventricular hypertrophy and decreasing partial arterial pressure of oxygen were also observed.

Conclusions: The present shunt-related model successfully simulated a hypertensive status in pulmonary circulation and reproduced the characteristic transition of pulmonary vasculopathy from reversibility to irreversibility within a relatively short period. Thus, this model could offer an alternative with low mortality and high reproducibility for investigations on the underling mechanisms of shunt-related pulmonary hypertension.

Keywords: 11; 20; 26.6; CSG; LCCA; LCSG; LEJV; MT; PASP; PH; RPALG; RVHI; RVSP; SD; SOG; Sprague-Dawley; combined surgery group; left cervical shunt group; left common carotid artery; left external jugular vein; mPAP; mean pulmonary arterial pressure; medial thickness; pulmonary arterial systolic pressure; pulmonary hypertension; right pulmonary artery ligation group; right ventricular hypertrophy index; right ventricular systolic pressure; sham operation group.