A comprehensive characterization of active expiration in freely behaving rats

Abstract

Blood gas disturbances caused by exposure to low oxygen (hypoxia) or high carbon dioxide levels (hypercapnia) lead to a compensatory increase in pulmonary ventilation. Among the motor changes supporting these reflex respiratory responses is the recruitment of abdominal muscles (ABD) during the expiratory phase, which can enhance expiratory airflow or alter the duration of the expiratory phase. In this study, we assessed the functional impact of ABD recruitment on metabolic, motor, and ventilatory parameters in unanesthetized, freely behaving animals. Sprague-Dawley Holtzman male adult rats (n=7) were instrumented to perform simultaneous recordings of pulmonary ventilation, body temperature, diaphragmatic and ABD activities, and O2 consumption during exposure to various levels of hypoxia (12-8% O2) and hypercapnia (3-7% CO2). We observed that hypoxia or hypercapnia conditions evoked AE; however, ABD recruitment did not occur during the entire exposure period, displaying an intermittent profile. The occurrence of AE during hypoxia and hypercapnia conditions was linked to additional increases in tidal volume when compared to periods without ABD activity (P<0.05) and showed no associations with changes in diaphragmatic burst amplitude. Analyses of flow-like patterns suggested that AE during hypoxia recruited expiratory reserve volume during late expiration, while under hypercapnia, it accelerated lung emptying and increased the expiratory flow peak during post-inspiration. We also observed that AE was associated with an increase in oxygen consumption and did not improve air convection requirement, suggesting that this motor behavior may influence other aspects of respiration that potentially improve alveolar ventilation and gas exchange. Key points summaryO_LIAbdominal recruitment during the expiratory phase, known as active expiration (AE), emerges during blood gas disturbances to enhance pulmonary ventilation; however, the effect of AE on metabolic, motor, and ventilatory parameters in freely behaving animals exposed to hypoxia or hypercapnia remains uncertain. C_LIO_LIBy simultaneously recording pulmonary ventilation, diaphragmatic and abdominal activities, and O2 consumption, we found that the occurrence of AE during hypoxia or hypercapnia exposure resulted in an additional increase in tidal volume. C_LIO_LIAE was not evident during all periods of exposure to hypoxia or hypercapnia, and its expression increased O2 consumption. C_LIO_LIAnalysis of flow-like signals suggested that AE during hypoxia recruits expiratory reserve volume in late expiration, while under hypercapnia, it facilitates lung emptying and increases the peak expiratory flow post-inspiration. C_LIO_LIDespite being similar from a motor perspective, the impact of AE on lung ventilation differs between hypoxia and hypercapnia in unanesthetized rats. C_LI