Cell Reports: Methods (Oct 2023)
A pneumonectomy model to study flow-induced pulmonary hypertension and compensatory lung growth
Abstract
Summary: In newborns, developmental disorders such as congenital diaphragmatic hernia (CDH) and specific types of congenital heart disease (CHD) can lead to defective alveolarization, pulmonary hypoplasia, and pulmonary arterial hypertension (PAH). Therapeutic options for these patients are limited, emphasizing the need for new animal models representative of disease conditions. In most adult mammals, compensatory lung growth (CLG) occurs after pneumonectomy; however, the underlying relationship between CLG and flow-induced pulmonary hypertension (PH) is not fully understood. We propose a murine model that involves the simultaneous removal of the left lung and right caval lobe (extended pneumonectomy), which results in reduced CLG and exacerbated reproducible PH. Extended pneumonectomy in mice is a promising animal model to study the cellular response and molecular mechanisms contributing to flow-induced PH, with the potential to identify new treatments for patients with CDH or PAH-CHD. Motivation: Unilateral pneumonectomy in rodents is a widely used animal model for investigating compensatory lung growth (CLG) and flow-induced pulmonary hypertension (PH). However, an important limitation lies in the rapid and complete restoration of lung volumes following the removal of a single lobe, which does not mimic the persistence observed in human pulmonary diseases. Given the high prevalence of developmental lung disease and the limited therapeutic options available for such patients, there is an urgent need to develop and characterize an animal model of CLG and PH that more accurately recapitulates disease reproducibility and persistence. In this study, we propose a simple and effective approach to enhance the traditional left pneumonectomy mouse model by employing a single-incision extended pneumonectomy technique that effectively addresses these gaps. This method exhibits robustness, reproducibility, and a broad adaptability for translational and mechanistic studies.
