Effects of GABA receptor blockade on the ventilatory response to hypoxia in hypothermic newborn piglets

Hypothermic newborn piglets have a depressed ventilatory response to hypoxi a, and this may be due to an increase in CNS gamma-aminobutyric acid (GABA) levels. To evaluate the effects of GABA(A) receptor blockade on the ventil atory response to hypoxia in hypothermic piglets, 31 anesthetized paralyzed mechanically ventilated newborn piglets (2-7 d) were studied at a brain te mperature of 38.5 +/- 0.5 degrees C [normothermia (NT), n = 15] or 34 +/- 0 .5 degrees C [hypothermia (HT), n = 16]. The central respiratory output was evaluated by measuring burst frequency and moving time average area of phr enic nerve activity. Measurements of minute phrenic output (MPO), arterial blood pressure, heart rate, oxygen consumption, and arterial blood gases we re obtained at room air and during 20 min of isocapnic hypoxia [fraction of expired oxygen (Fio(2)) = 0.10], After 10 min of hypoxia, a bolus injectio n of 20 mu L of bicuculline methiodide (BM; 10 mu g) or Ringer's solution w as administered into the cisterna magna over a I-min period, and the piglet s remained in hypoxia for an additional 10 min. There was an initial increa se of 50 +/- 6% in MPO during the first minute of hypoxia followed by a dec rease to values 24 +/- 8% above baseline at 10 min in the NT group. In cont rast, in the HT group, the initial increase in MPO with hypoxia was elimina ted, and, at 10 min, there was a decrease to a mean value 35 +/- 4% below b aseline level (NT versus HT, p < 0.03). After administration of BM, a signi ficant increase in MPO with hypoxia was observed in both groups compared wi th their placebo groups (p < 0.002 in NT-BM group, p < 0.0001 in HT-BM grou p). However, the magnitude of the increase in MPO during hypoxia was signif icantly greater in the HT group after administration of BM (NT versus HT, p < 0.0001). Changes in oxygen consumption, arterial blood pressure, heart r ate, pH, partial pressure of oxygen (Pao(2)), and base excess with hypoxia were not different between NT and HT groups before and after the administra tion of BM. The cardiorespiratory response to hypoxia was not modified afte r administration of Ringer's solution to NT and HT placebo groups. These da ta suggest that the depression in hypoxic ventilatory response produced by HT is in part modulated by an increased CNS GABA concentration.