A surgical mouse model of neonatal right ventricular outflow tract obstruction by pulmonary artery banding

Debao Li; Haifa Hong; Minghui Li; Xiuxia Xu; Shoubao Wang; Yingying Xiao; Sixie Zheng; Zheng Wang; Yi Yan; Hao Chen; Chunxia Zhou; Hao Zhang; Qi Sun; Lincai Ye

doi:10.1016/j.healun.2023.10.009

A surgical mouse model of neonatal right ventricular outflow tract obstruction by pulmonary artery banding

J Heart Lung Transplant. 2024 Mar;43(3):496-507. doi: 10.1016/j.healun.2023.10.009. Epub 2023 Oct 14.

Authors

Debao Li¹, Haifa Hong², Minghui Li³, Xiuxia Xu⁴, Shoubao Wang⁵, Yingying Xiao², Sixie Zheng⁶, Zheng Wang⁶, Yi Yan⁷, Hao Chen⁶, Chunxia Zhou⁶, Hao Zhang⁸, Qi Sun⁹, Lincai Ye¹⁰

Affiliations

¹ Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Pediatric Surgery, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
² Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
³ Department of Cardiovascular Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
⁴ Department of Radiology, Huangpu Branch, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ Department of Plastic Surgery, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁶ Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁷ Shanghai Clinical Research Center for Rare Pediatric Diseases, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Research Center for Pediatric Cardiovascular Diseases, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Heart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁸ Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Clinical Research Center for Rare Pediatric Diseases, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Research Center for Pediatric Cardiovascular Diseases, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Heart Center and Shanghai Institute of Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Institute for Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: zhanghao@scmc.com.cn.
⁹ Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: empyrealheights@163.com.
¹⁰ Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Institute for Pediatric Congenital Heart Disease, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: ylc717@163.com.

PMID: 37839791
DOI: 10.1016/j.healun.2023.10.009

Abstract

Backgroud: Diseased animal models play an extremely important role in preclinical research. Lacking the corresponding animal models, many basic research studies cannot be carried out, and the conclusions obtained are incomplete or even incorrect. Right ventricular (RV) outflow tract (RVOT) obstruction leads to RV pressure overload (PO) and reduced pulmonary blood flow (RPF), which are 2 of the most important pathophysiological characteristics in pediatric cardiovascular diseases and seriously affect the survival rate and long-term quality of life of many children. Due to the lack of a neonatal mouse model for RVOT obstruction, it is largely unknown how RV PO and RPF regulate postnatal RV and pulmonary development. The aim of this study was to construct a neonatal RVOT obstruction mouse model.

Methods and results: Here, we first introduced a neonatal mouse model of RVOT obstruction by pulmonary artery banding (PAB) on postnatal day 1. PAB induced neonatal RVOT obstruction, RV PO, and RPF. Neonatal RV PO induced cardiomyocyte proliferation, and neonatal RPF induced pulmonary dysplasia, the 2 features that are not observed in adult RVOT obstruction. As a result, PAB neonates exhibited overall developmental dysplasia, a sign similar to that of children with RVOT obstruction.

Conclusions: Because many pediatric cardiovascular diseases are associated with RV PO and RPF, the introduction of a neonatal mouse model of RVOT obstruction may greatly enhance our understanding of these diseases and eventually improve or save the lives of many children.

Keywords: Tetralogy of Fallot; cardiomyocyte proliferation; congenital heart disease; pressure overload; pulmonary dysplasia; pulmonary hypertension; right ventricle.

MeSH terms

Adult
Animals
Cardiac Surgical Procedures* / methods
Cardiovascular Diseases*
Child
Humans
Infant, Newborn
Mice
Pulmonary Artery / surgery
Quality of Life
Tetralogy of Fallot* / surgery
Ventricular Outflow Obstruction* / etiology
Ventricular Outflow Obstruction* / surgery
Ventricular Outflow Obstruction, Right*