A Mouse Model of Neonatal Continuous Positive Airway Pressure Administration and the Precision Lung Slice Method for Measuring Airway Contractility

Peter  M. MacFarlane; Catherine A. Mayer; Christina Pabelick; YS Prakash; Richard J. Martin

doi:10.3791/68643

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Method Article

A Mouse Model of Neonatal Continuous Positive Airway Pressure Administration and the Precision Lung Slice Method for Measuring Airway Contractility

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DOI:

10.3791/68643

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March 13th, 2026

Peter M. MacFarlane¹^,² , Catherine A. Mayer¹^,² , Christina Pabelick³^,⁴ , YS Prakash³^,⁴ , Richard J. Martin¹^,²

¹Department of Pediatrics, UH Rainbow Babies & Children's Hospital, ²Department of Pediatrics, Case Western Reserve University School of Medicin, ³Department of Anesthesiology & Perioperative Medicine, Mayo Clinic, ⁴Department of Physiology and Biomedical Engineering, Mayo Clinic

Summary

We demonstrate a noninvasive method to deliver varying levels of CPAP to unanesthetized neonatal mice. The technique is intended to partially mimic CPAP administration for many preterm infants to assess its effects on lung development. We also demonstrate CPAP's effects on airway contractility using the precision lung slice method.

Abstract

Mechanical forces associated with positive-pressure respiratory support used in the intensive care of preterm infants can have both positive and inadvertent consequences for lung development. Positive pressure support improves pulmonary gas exchange, limits atelectasis, and improves systemic oxygenation, but the injurious effects of invasive modalities, such as mechanical ventilation, on lung development are also well known. However, there are major gaps in our understanding of the adverse effects of less invasive forms of ventilation. Here, continuous positive airway pressure (CPAP) is one of the most common respiratory support modalities, representing the least invasive of the positive pressure spectrum. A major limitation in studying human airway development is the lack of age-appropriate models and the ability to administer CPAP to small neonatal animals. We resolved this problem by developing a mouse model of neonatal CPAP delivered daily to awake, un-anesthetized newborn mice -- a model that utilizes clinically relevant CPAP levels at a stage of mouse lung development that corresponds with preterm infants when they are likely to receive CPAP in the ICU. Here, we demonstrate our CPAP model, which includes a convenient, custom-designed system that can deliver CPAP non-invasively to the un-anesthetized newborn with easily adjustable levels. We also provide a demonstration of the precision cut lung slice method for the measurement of airway hyperreactivity ex vivo. The PCLS is described here because it provides a convenient functional readout of the pulmonary system, which can be technically challenging in small (neonatal) animal models, and also has wide applicability to other models unrelated to CPAP. We show data demonstrating that CPAP elicits airway hyperreactivity, which may have important clinical implications for the choice of respiratory support modality in the intensive care of preterm infants.

Introduction

Respiratory-related concerns, such as apnea and respiratory distress, for many preterm infants require life-saving modes of respiratory support, which, unfortunately, contribute to infant morbidity and prolonged hospital stays. Supplemental O₂ and positive pressure respiratory support, including mechanical ventilation (MV) and less-invasive CPAP, are common respiratory support modalities. However, the major short- and long-term problem for survivors of the critical period in prematurity remains chronic bronchial airway disease¹^,²^,³^,⁴