Disentangling Hypoxic Ventilatory Depression from Metabolic Depression in Neonatal Rats

Department or Program

Biology

Abstract

Neonatal mammals exhibit a biphasic hypoxic ventilatory response (HVR), consisting of an initial increase in ventilation which is typically followed by hypoxic ventilatory depression (HVD). The mechanisms underlying HVD remain unclear, although it has been suggested that it may be caused by an associated decrease in metabolic rate. If HVD and metabolic depression are causally linked, I hypothesized that changes in ventilation and metabolism would be temporally linked during acute hypoxia in neonatal rats. Measurements of metabolic rate by respirometry are technically challenging during the early HVR due to hyperventilation and excess CO2 excretion. In Experiment 1, I used the P2X receptor antagonist PPADS to attenuate carotid body signaling and enable continuous measurement of V̇CO2 in 3-4 day old rats during a 15-minute exposure to hypoxia (12% O2). As expected, PPADS reduced ventilation (measured by head-body plethysmography) throughout hypoxia and attenuated the initial ventilatory response. The reductions in both V̇CO₂ and V̇E were significant, occurring in parallel and dropping below baseline levels by the three-minute mark of hypoxic exposure. In Experiment 2, I evaluated whether body temperature (Tb) could serve as a proxy for metabolic depression during the early phase of the HVR. After implanting a microchip transponder in the interscapular region to monitor body temperature, I measured changes in breathing and metabolic rate as in Experiment 1. At 33°C, decreases in Tb paralleled reductions in ventilation and V̇CO₂ with changes in all variables occurring between 1-3 minutes of hypoxic exposure. At 28°C, Tb once again appeared to decrease in hypoxia at the same time as the decreases in ventilation and V̇CO₂. Across experiments, hypoxia elicited correlated, but not strictly proportional, changes in ventilation and metabolic rate. These findings are consistent with a causal link between hypoxic metabolic depression and HVD. However, separate but coordinated changes in both metabolic rate and ventilation cannot be ruled out.

Level of Access

Restricted: Archival Copy [No Access]

First Advisor

Bavis, Ryan

Date of Graduation

5-2026

Degree Name

Bachelor of Science

Number of Pages

81

Components of Thesis

1 pdf file

Archival Copy

Document unavailable for viewing.

Share

COinS