Role of GABA on the Ventilatory Response to Hypoxia during Lactic Acid Infusion

Abstract 1767 Pulmonary: Control of Breathing Poster Symposium, Tuesday, 5/4

We have previously demonstrated that the central inhibitory amino acid neurotransmitter GABA mediates in part the hypoxic ventilatory depression observed in newborn piglets. The ventilatory response to hypoxia is significantly attenuated during lactic acid - induced metabolic acidosis (Pediatr Res 43:280A, 1998). To evaluate whether changes in the CNS GABA levels play a role in the attenuation in the ventilatory response during metabolic acidosis, 20 awake, unanesthetized and chronically instrumented newborn piglets (mean±SD; age, 6.3±2.3 d; weight, 2.1±0.4 kg) were studied before and during an infusion of either dextrose as a placebo solution, (PL; n=8) or lactic acid (LA; n=12). The dose of LA was titrated to induce a stable metabolic acidosis with a base excess of -8 to -12 mEq/L. Minute ventilation (V_E), arterial blood pressure (ABP), heart rate (HR), arterial blood gases and CNS GABA levels were measured during normoxia (RA) and 15 min of hypoxia (Hy; FiO₂=0.10). Extracellular GABA levels were measured in the nucleus tractus solitarius (NTS) by microdialysis. Samples were collected at 5 min intervals and analyzed using HPLC with electrochemical detection. Data were analyzed by repeated measures ANOVA. Mean±SD values for V_E (% of RA) and GABA (% of RA) were as follows: (Table)

Table 1 No caption available

A significant increase in basal V_E was observed during LA infusion but the ventilatory response to hypoxia was markedly attenuated. A significant increase in NTS GABA levels with hypoxia was noted during LA infusion. A significant negative linear correlation was observed between changes in V_E and GABA levels during hypoxia (r = 0.53, P < 0.005). Changes in V_E and GABA levels during hypoxia were not different before and during PL infusion. Changes in ABP, HR, PaO₂ and PaCO₂ during hypoxia were not statistically different before and during PL or LA infusion. These data suggest that the attenuation in the ventilatory response to hypoxia observed during LA - induced metabolic acidosis in newborn piglets is in part mediated by an increase in the CNS GABAergic activity.