Effects of GABA Receptor Blockade on the Ventilatory Response to Hypoxia during Lactic Acid Infusion in Newborn Piglets

Abstract 1768 Pulmonary: Control of Breathing Poster Symposium, Tuesday, 5/4

We have previously demonstrated that newborn piglets experience an attenuation in the ventilatory response to hypoxia during induced metabolic acidosis (Pediatr Res 43: 280A, 1998). It has been described that CNS inhibitory amino acid neurotransmitter GABA levels increase during brain hypoxia, ischemia and lactic acidosis. These increased CNS GABA levels may mediate the depression in ventilation observed during metabolic acidosis. To assess whether GABA α receptor blockade can reverse the hypoxic ventilatory depression during metabolic acidosis, 11 awake, unanesthetized and chronically instrumented newborn piglets (mean±SD; age, 5.7±1.4 d; weight, 2.1±0.3 kg) were studied during steady state metabolic acidosis induced with lactic acid (LA) infusion (BE of -8 to -12 mEq/L). Minute ventilation (V_E), arterial blood pressure (ABP), heart rate (HR) and arterial blood gases were measured during normoxia (RA) and 15 min of hypoxia (FiO₂=0.10), before and during an infusion of ringer solution (R, n=6) or the GABA antagonist, bicuculline methochloride (BM, n=5). BM (100µM) was continuously administered into the nucleus tractus solitarius (NTS) through a microdialysis probe. Data were analyzed by repeated measures ANOVA. Mean±SE values for V_E (ml/kg/min) were as follows: (Table)

Table 1 No caption available

The increase in basal ventilation observed in both groups during LA infusion was not modified by the administration of R or BM. There was a marked attenuation in ventilation during hypoxia in the R group, whereas the ventilatory response to hypoxia was significantly increased and sustained in the BM group (P<0.05). Changes in ABP, HR, PaO₂, PaCO₂ and BE during hypoxia were not different between R and BM groups. These results demonstrate that the attenuation in the ventilatory response to hypoxia observed during LA - induced metabolic acidosis in newborn piglets is in part due to an increase in the endogenous GABA levels in the NTS.