Effects of hypoxia and hypothermia on the end-inspiratory pause and Hering-Breüer reflex in the neonatal tammar wallaby
Respiratory Research volume 2, Article number: P12 (2001)
When cooled in normoxia newborn rats decreased body temperature (Tb), increased metabolic rate and weakened the intensity of the vagally mediated Hering-Breüer inspiratory inhibition reflex (HB reflex) . On the other hand cooling in hypoxia decreased both Tb and metabolic rate and had no effect on HB reflex intensity . This suggested that in newborn rats the effect of cooling on the strength of the HB reflex was not attributable to Tb per se but to the corresponding changes in metabolic rate . Nevertheless, in normoxia the drop in Tb with cooling, via the Q10 effect, could oppose the changes in metabolic rate induced by thermogenesis, and the hypoxia per se could be expected to provide a 'drive' through its effect on the peripheral chemoreceptors. To clarify the effects of hypothermia and hypoxia on the HB reflex in the absence of thermogenesis we examined the ectothermic neonatal tammar wallaby (Macropus eugenii). As newborn marsupials breathe with a pronounced end-inspiratory pause [3,4], the result of vagally controlled laryngeal closure , the effect of cooling and hypoxia on the end-inspiratory pause was also examined.
Neonates (aged 2–3 weeks, mass ~2.5 g) were studied at Tb of 36.5 (normothermia), 32, 28 and 20°C in normoxia or hypoxia (10% O2). The rate of oxygen consumption (VO2), breathing pattern and ventilation (??E) were measured as previously described . Applying a vacuum across the body until the first inspiratory effort induced the HB reflex, quantified as the inhibitory ratio (IR) of the expiratory time during lung inflation compared to the expiratory time during spontaneous breathing (TE).
At 36.5°C in normoxia the tammar neonate exhibited a marked IR to maintained lung inflations at -5 and -10 cm H2O. Acute hypoxia invoked a hyperpnea (+42%) and hypometabolism (-30%) and reduced the IR by ~50% at -10 cm H2O and abolished it at -5 cm H2O. This is in agreement with the effects of hypoxia on hyperventilation and the HB reflex in 8-day-old rat pups  which possess a greater chemosensitivity than newborn rats. In normoxia decreased Tb was associated with a decrease in VO2 yet ??E/VO2 remainedunchanged (~32) to that at 36.5°C; the decrease in ??E was contributed to by an increase in TE, primarily the end-inspiratory pause. Associated with the increase in expiratory time was a failure to elicit a HB reflex at either -5 or -10 cm H2O. At lower temperatures exposure to hypoxia maintained the hyperventilation (??E/VO2 ~62) seen at 36.5°C, though at these temperatures this was achieved solely through a hypometabolic response. Whether the lack of hyperpneic response was affected by the affect of hypothermia on chemo-afferents  is unknown but maintenance of ??E/VO2 during hypothermia in the 2–3 week old tammar wallaby suggests that, relative to metabolic rate, respiratory gain, which is centrally controlled, is not depressed. Additionally, hypothermia prolongs the end-inspiratory pause presumably through temperature effects on neural function  and that these appear to predominate the vagally mediated HB reflex.
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Frappell, P., MacFarlane, P. Effects of hypoxia and hypothermia on the end-inspiratory pause and Hering-Breüer reflex in the neonatal tammar wallaby. Respir Res 2 (Suppl 1), P12 (2001). https://doi.org/10.1186/rr128