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

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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.

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Acknowledgements

This study was supported by the National Key Research and Development Program of China (No. 2017YFC1308103), Shanghai Health and Family Planning Commission Research Program (No. 201640405) and Shanghai Pudong New Area Health System Medical Youth Training Program (No. PWRq2017-09).

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Author notes

  1. Qiancheng Luo and Xiuxia Xu contributed equally to this work.

Authors and Affiliations

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

    Qiancheng Luo, Xiaomin He, Qi Sun & Jinghao Zheng

  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

    Xiuxia Xu

  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

    Shoubao Wang

Authors
  1. Qiancheng Luo
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  2. Xiuxia Xu
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  3. Xiaomin He
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  4. Shoubao Wang
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  5. Qi Sun
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  6. Jinghao Zheng
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Contributions

QL and XX performed the experiments and analyzed the data. QL drafted the manuscript. SW and XH conducted PAB operation and revised the manuscript. QS and JZ designed and supervised the research. All authors read, approved and contributed to the final manuscript.

Corresponding authors

Correspondence to Qi Sun or Jinghao Zheng.

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The authors declare that they have no conflict of interest.

Ethical approval

All experiments in studies were reviewed and approved by the Ethics Committee of Shanghai Children’s Medical Center. All surgical procedures were performed under anesthesia and in adherence with the guidelines from the Committee for the Care and Use of Laboratory Animals.

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Luo, Q., Xu, X., He, X. et al. Pulmonary Hypoplasia Resulting from Pulmonary Artery Banding in Infancy: A Neonatal Rat Model Study. Pediatr Cardiol 42, 397–407 (2021). https://doi.org/10.1007/s00246-020-02495-9

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  • DOI: https://doi.org/10.1007/s00246-020-02495-9

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