Studying Flow-induced Pulmonary Hypertension and Compensatory Lung Growth :

Understanding pulmonary hypertension (PH), pulmonary hypoplasia, and compensatory lung growth (CLG) is essential for developing treatments for complex pulmonary diseases. Tsijis et al (2023) developed a novel extended pneumonectomy (EP) mouse model to investigate the relationship between pulmonary blood flow, lung growth, and pulmonary hypertension.

A New Mouse Model of Pulmonary Hypertension

Conditions such as congenital diaphragmatic hernia (CDH) and congenital heart disease (CHD) can cause pulmonary hypoplasia, impaired alveolarization, and pulmonary arterial hypertension (PAH). Reliable animal models are therefore critical for understanding these mechanisms.

The EP model involves removing the left lung and right caval lobe, limiting compensatory lung growth and producing reproducible flow-induced pulmonary hypertension.

Compared with traditional pneumonectomy, EP mice showed:

• Reduced lung volume, inspiratory capacity, and total lung capacity (TLC)
• Increased mechanical work of breathing
• Impaired exercise performance
• More severe pulmonary hypertension
• Reduced alveolarization and increased vascular remodeling

These changes make the EP model particularly useful for investigating the mechanisms linking altered pulmonary blood flow, compensatory lung growth, and pulmonary vascular remodeling.

Measuring Lung Function with flexiVent

The flexiVent system was used to assess pulmonary function, including inspiratory capacity, total lung capacity, and mechanical work of breathing.

Pressure-volume measurements were used to calculate TLC, with results analyzed using flexiWare software and normalized to body weight.

Combining quantitative lung function measurements with histological and molecular analyses provides a comprehensive approach to studying pulmonary hypertension and impaired lung growth.

Advancing Pulmonary Research

The extended pneumonectomy model offers a reproducible preclinical model of flow-induced pulmonary hypertension and impaired compensatory lung growth. When combined with tools such as flexiVent, researchers can investigate changes in lung mechanics, lung development, and pulmonary vascular remodeling, helping advance our understanding of pulmonary hypoplasia and PAH.