Recovery of Ventilatory and Metabolic Responses to Hypoxia after Chronic Hypoxia in Neonatal Rats

Abstract

Chronic hypoxia (CH) from birth blunts the hypoxic ventilatory response (HVR) in newborn rats, but there is conflicting evidence as to whether (or how quickly) the HVR recovers after these rats are returned to room air. In this study, Sprague-Dawley rats were exposed to either 21% O2 (Control) or 12% O2 (CH) for the first 3 postnatal days. Breathing and metabolism were studied using head-body plethysmography and respirometry immediately after the 3 days of CH (i.e., at P3) or after 1, 4-5, or 7 days of recovery in room air (i.e., at P4, P7-8, or P10). The early phase of the HVR was blunted in CH rats at P3 (13.7± 2.3 vs. 30.6±3.4 % increase from baseline during 12% O2), and the HVR was more biphasic in CH rats after 1 day of recovery. However, no significant differences in the HVR were observed between treatment groups after 3-4 or 7 days of recovery. Males and females showed similar patterns. Changes in ventilation during hypoxia were strongly biphasic in the younger age groups: ventilation increased initially, but this was followed by a gradual decline in ventilation towards or below baseline levels. However, when accounting for metabolic depression, all age groups continued to hyperventilate during the late phase of the HVR [i.e., the ratio of ventilation to CO2 production (CO2 convection requirement) remained elevated relative to baseline values]. The CO2 convection requirement response to hypoxia did not differ between treatment groups during the late phase of the HVR at any age, but metabolism and CO2 convection requirement could not be determined during the early phase of the HVR due to non-steady state conditions. In conclusion, 3 days of CH produces only a transient blunting of the HVR in newborn rats. Longer CH exposures may be required to elicit persistent changes in the HVR or, alternatively, this plasticity may not be revealed until after puberty. Supported by NIH grant P20 GM-103423 (Maine INBRE). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.