260 - Effects of Chronic Neonatal Hyperoxia-Induced Bronchopulmonary Dysplasia on Breathing, Growth and Energy Expenditure in Mice

Sunday, April 30, 2023

3:30 PM – 6:00 PM ET

Poster Number: 260
Publication Number: 260.34

Jeffrey Segar, Medical College of Wisconsin, Milwaukee, WI, United States; Brooke B. Dir, Medical College of Wisconsin, Wauwatosa, WI, United States; Connie Grobe, Medical College of Wisconsin, Milwaukee, WI, United States; John J. Reho, Medical College of Wisconsin, Milwaukee, WI, United States; Justin L.. Grobe, Medical College of Wisconsin, Milwaukee, WI, United States; Gary C. Mouradian, Medical College of Wisconsin, Milwaukee, WI, United States

Presenting Author(s)

JS

Jeffrey Segar, MD (he/him/his)

Professor
Medical College of Wisconsin
Milwaukee, Wisconsin, United States

Background: Growth failure is common in infants with bronchopulmonary dysplasia (BPD) and is associated with impaired breathing, poor growth and increased resting metabolic rate (RMR). Whether growth failure and increased RMR are a consequence of underlying BPD lung pathology per se or a consequence of clinical interventions is unknown.

Objective: Test the hypothesis that hyperoxia-induced BPD-like lung injury negatively impacts breathing, growth, and energy expenditure in male mice.

Design/Methods:

Cross-fostered C57BL/6J mice were exposed to chronic hyperoxia (HX; 70% O₂, n=12) or normoxia (NX, n=13) in the neonatal period (postnatal day (P) 0-14). Breathing was assessed by plethysmography; body mass, body composition, food and water intake, physical activity and energy expenditure were assessed using time-domain nuclear magnetic resonance and multiplexed metabolic phenotyping (Promethion, Sable Systems). Data were analyzed by ANOVA or generalized linear model to account for relevant covariates.

Results:

: Inflation-fixed HX lungs at 9 weeks age displayed a 30% decrease in alveolar surface area vs NX lungs (p< 0.05). In response to acute hypoxia (10 min; 12% O₂), HX mice had a reduced ventilatory response (89±4 vs 108±6 % of room air breathing; p< 0.05) and drive to breathe (tidal volume/inspiratory time; 0.76±0.04 vs 0.98±0.06 mL/s; p< 0.05) due to longer inspiratory times (170±9 vs 132±6 ms, p< 0.05). Despite the differences in lung function, no differences in body composition (body, fat and fat-free masses, and total body water) were observed at P21, 6wks, or 8wks of life. Furthermore, there were no differences in ingestive behaviors, or total or resting aerobic heat production (kcal/h) at 8 wks of age. HX mice had reduced locomotor activity (154±11 vs 199±10 m/d; p< 0.05), consistent with reduced exercise capacity.

Conclusion(s): These data document the impact of BPD-like lung injury on key physiological parameters in mice. Changes in ventilatory control are consistent with those reported in adults with BPD. The absence of effect of HX-induced BPD on growth and energy expenditure suggests that BPD pathology per se does not drive increased RMR or growth failure. We speculate that sodium depletion resulting from diuretic therapy, which is common for this condition and known to impact infant growth, may be an important contributor to growth failure in infants with BPD.