Novel method for conscious airway resistance and ventilation estimation in neonatal rodents using plethysmography and a mechanical lung

• We investigated components of the WBP chamber pressure waveform in small animals.
• A novel ‘mechanical lung’ was developed to mimic the breathing of a neonatal mouse.
• We found that WBP is unsuitable for accurately characterizing VT in neonatal mice.
• We present a novel in vivo, noninvasive method for airway resistance determination.

In unrestrained whole body plethysmography, tidal volume is commonly determined using the barometric method, which assumes that temperature and humidity changes (the ‘barometric component’) are solely responsible for breathing-related chamber pressure fluctuations. However, in small animals chamber pressure is also influenced by a ‘mechanical component’ dependent on airway resistance and airflow. We devised a novel ‘mechanical lung’ capable of simulating neonatal mouse breathing in the absence of temperature or humidity changes. Using this device, we confirm that the chamber pressure fluctuations produced by breathing of neonatal mice are dominated by the mechanical component, precluding direct quantitative assessment of tidal volume. Recognizing the importance of airway resistance to the chamber pressure signal and the ability of our device to simulate neonatal breathing at different frequencies and tidal volumes, we invented a novel in vivo, non-invasive method for conscious airway resistance and ventilation estimation (CARVE) in neonatal rodents. This technique will allow evaluation of developmental, pathological and pharmaceutical effects on airway resistance.