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Updated: Jun 8, 2026

Development of a Neonatal Piglet Acute Lung Injury Model Recreating the Early Environment of Preterm Infant Lungs
Published on: October 31, 2025
Postnatal ventilatory response to CO₂ in awake piglets
M R Dwinell1, G E Hogan, E Sirlin
1Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. mrdwinel@mcw.edu
Insights
The ventilatory response to carbon dioxide (CO₂) in piglets does not change significantly between postnatal days 1 and 28. This finding suggests that a critical developmental period for CO₂ response is not linked to SIDS risk in piglets.
Area of Science:
- Physiology
- Developmental Biology
- Respiratory Science
Background:
- Abnormal ventilatory responses to elevated carbon dioxide (CO₂) during postnatal development are a potential risk factor for Sudden Infant Death Syndrome (SIDS).
- A critical developmental period for ventilatory control has been previously suggested in piglets between 10 and 15 days of age.
Purpose of the Study:
- To investigate the hypothesis that the ventilatory response to hypercapnia (elevated CO₂) is attenuated in awake piglets between 10 and 15 postnatal days.
- To determine if repeated exposure to CO₂ affects the ventilatory response during early development.
Main Methods:
- Ventilatory response to 5% inspired CO₂ was measured in piglets from postnatal day 1 to 28.
- Piglets were exposed to CO₂ daily, every 3rd day, or only after postnatal day 20 to assess the impact of exposure frequency.
- Ventilation was normalized to body weight (V˙(E), ml/min/kg).
Main Results:
- Room air ventilation normalized to body weight declined with increasing postnatal age in all groups.
- The ventilatory response to 5% inspired CO₂ was present from birth and showed no significant age-dependent change between postnatal days 1 and 28 (p > 0.1).
- Neither daily nor every-3rd-day exposure to 5% inspired CO₂ altered the ventilatory response during the studied developmental period.
Conclusions:
- The previously suggested critical developmental period in piglets (10-15 days) is not characterized by an attenuated ventilatory response to 5% inspired CO₂.
- These findings indicate that changes in CO₂ responsiveness are not the primary factor explaining SIDS risk during this specific developmental window in piglets.
Abstract:
Abnormal ventilatory responses to increased levels of inspired CO₂ during postnatal development may pose a risk for Sudden Infant Death Syndrome, primarily during periods of vulnerability. The purpose of this study was to test the hypothesis that in awake piglets the ventilatory response to hypercapnia would be attenuated between 10 and 15 days of age relative to younger and older ages. To test this hypothesis, we measured the ventilatory response to 5% inspired CO₂ in piglets from postnatal (PN) days 1 through PN28. Piglets were divided into groups and exposed to 5% CO₂ daily, every 3rd day or on and after PN20-21 only to avoid any plasticity that may result from repeated exposure to CO₂. Room air ventilation normalized to body weight (V˙(E), ml/min/kg) declined with postnatal age in piglets from all groups. The ventilatory response to 5% inspired CO₂ (expressed as % change from control) was present at birth, and we did not find an age-dependent change from PN1 to PN28 (p > 0.1). In addition, we did not find that repeated exposure (daily or every 3rd day) to 5% inspired CO₂ altered the ventilatory response during this period of development. We conclude that the previously documented apparent critical period of development in piglets between 10 and 15 days of age is not associated with attenuation of the ventilatory response to 5% inspired CO₂.

