Effects of GABA Receptor Blockade on the Ventilatory Response to Hypoxia in Hypothermic Newborn Piglets. † 1624

Hypothermic newborn piglets have a depressed ventilatory response to hypoxia and this may be due to an increase in CNS GABA. In order to evaluate the effects of GABAα receptor blockade on the ventilatory response to hypoxia in hypothermic piglets, 32 anesthetized, paralyzed, mechanically ventilated newborn piglets (2-7 days) were studied at a brain temperature of 39.0±0.5°C (Normothermia, NT, n=16) and 34±0.5°C(Hypothermia, HT, n=16). The central respiratory output was evaluated by measuring burst frequency and moving time average area of phrenic nerve activity. Measurements of minute phrenic output (MPO), arterial blood pressure(ABP), heart rate (HR), oxygen consumption (VdotO₂) and arterial blood gases were obtained at room air (RA) and during 20 min of isocapnic hypoxia(FiO₂ =0.10). After 10 min of hypoxia, a bolus injection of 20 μl bicuculline methiodide (BM; 10 μg) or Ringer solution was administered into the cisterna magna over a 1-min period and the piglets remained in hypoxia for an additional 10 min. Mean±SE values for MPO (au/min) and% change(Δ) from RA (Pre-BM) or 10′ of hypoxia (Post-BM) were as follows:Table MPO decreased significantly with hypoxia before BM infusion in HT group compared to NT group (P<0.0001). Although there was a significant increase in MPO with hypoxia in both groups post-BM, this increase was significantly greater in HT group (P<0.008). Changes in VdotO₂, ABP, HR, pH, PaO₂ and BE with hypoxia were not different between NT and HT groups post-BM. The cardiorespiratory response to hypoxia was not modified after Ringer solution administration to NT and HT placebo groups. These data suggest that the depression in hypoxic ventilatory response produced by hypothermia is due to an increase in CNS GABA concentration.

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