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A Neonatal Rat Model Of Pulmonary Vein Stenosis
Debao Li, Qi Sun, lincai Ye;
Department of Thoracic and Cardiovascular Surgery, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China, Shanghai, China
BACKGROUND:Pulmonary vein stenosis (PVS), one of the most challenging clinical problems in congenital heart disease, leads to secondary pulmonary arterial hypertension (PAH) and right ventricular (RV) hypertrophy. Due to the lack of a rodent model, the mechanisms underlying PVS and its associated secondary effects are largely unknown, and treatments are minimally successful. This study created a neonatal rat PVS model with the aim of increasing understanding of the mechanisms and possible treatments for PVS
METHODS:PVS was created at postnatal day 1 (P1) by banding pulmonary veins that receive blood from the right anterior and mid lobes. The condition was confirmed using echocardiography, computed tomography (CT), gross anatomic examination, hematoxylin and eosin (H&E) staining, and immunofluorescence. Lung and RV remodeling under the condition of PVS were evaluated using H&E staining and immunofluorescence.
RESULTS:At P21, echocardiography revealed a change in wave form and a decrease in pulmonary artery acceleration time—indicators of PAH—at the transpulmonary valve site in the PVS group. CT at P21 showed a decrease in pulmonary vein diameter in the PVS group. At P30 in the PVS group, gross anatomic examination showed pulmonary congestion, H&E staining showed wall thickening and lumen narrowing in the upstream pulmonary veins, and immunofluorescence showed an increase in the smooth muscle layers in the upstream pulmonary veins. In addition, at P30 in the PVS group, lung remodeling was evidenced by hyperemia, thickening of pulmonary small vessel walls and smooth muscle layers, and reduction of the number of alveoli. RV remodeling was evidenced by an increase in RV free wall thickness.
CONCLUSIONS:A neonatal rat model of PVS was successfully established, showing secondary lung and RV remodeling. This model may serve as a useful platform for understanding the mechanisms and treatments for PVS.
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