Pulmonary Hypoplasia Resulting from Pulmonary Artery Banding in Infancy: A Neonatal Rat Model Study

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ORIGINAL ARTICLE

Pulmonary Hypoplasia Resulting from Pulmonary Artery Banding in Infancy: A Neonatal Rat Model Study Qiancheng Luo1   · Xiuxia Xu2 · Xiaomin He1 · Shoubao Wang3 · Qi Sun1 · Jinghao Zheng1 Received: 17 August 2020 / Accepted: 30 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract The aim of this study was to establish a neonatal rat model of decreased pulmonary blood flow (PBF) for studying pulmonary pathophysiological changes in newborn lung development with reduced PBF. Horizontal thoracotomy surgery with banding of the main pulmonary artery (PA) was performed on 30 rats in the PA banding (PAB) group and without banding on another 30 rats in the sham group within 6 h after birth. The body growth and mortality were recorded. Constriction of PA was checked by echocardiography on postnatal day 7 (P7). Lung morphology was assessed with computed tomography scanning and three-dimensional reconstruction. Histological differences of two groups were evaluated using hematoxylin and eosin (H&E) staining, Masson’s trichrome staining, TdT-mediated dUTP nick-end labeling assay, and CD31 labeling with microscopic examination. PA ultrasound confirmed the establishment of constriction on P7. Relative to the sham group, the neonates’ physical growth, survival fraction, and lung geometry volume were decreased in the PAB group over time (p < 0.05). Histologic appearance with reduced PBF characterized a markedly simplified alveolarization with noted lower radial alveolar count and alveolar septal thickness in the PAB group (p < 0.0001), pulmonary arteries with thinner/uneven membranous layers and smaller lumina. The deficient alveolar capillary bed, enhanced pulmonary collagen deposition, and increased apoptotic alveolar epithelium were significant in the PAB group compared to the sham group (p < 0.0001). A neonatal rat PAB model demonstrated that PBF reduction during early infancy impairs alveolarization and pulmonary microvasculature. Keywords  Pulmonary artery banding · Pulmonary blood flow · Pulmonary hypoplasia · Alveolarization · Microvasculature

Introduction

Qiancheng Luo and Xiuxia Xu contributed equally to this work. * Qi Sun [email protected] * Jinghao Zheng [email protected] 1



Department of Cardiothoracic Surgery, Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, 1678 Dongfang Rd., Shanghai 200127, China

2



Department of Radiology, Huangpu Branch, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 58 Puyu East Rd., Shanghai 200011, China

3

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Rd, Shanghai 200011, China



Pulmonary artery banding (PAB) has been used as a preferred palliative operation either to prevent pulmonary hypertension, stabilize tricuspid regurgitation, or train the left ventricle in congenital heart diseases (CHDs) [1–3]. The procedure was adopted to establish righ