Role Of Glutamate On The Ventilatory Response To Hypoxia During Lactic Acid Infusion In Newborn Piglets. ♦ 1638

The hyperventilatory response to hypoxia is mediated by an increase in the CNS glutamate (GLU) levels. Metabolic acidosis decreases CNS GLU levels and thus may affect the ventilatory response to hypoxia. To evaluate the role of GLU on the ventilatory response to hypoxia during metabolic acidosis, 14 awake, unanesthetized and chronically instrumented newborn piglets(mean±SD; age, 6.6±3.2; wt, 1.9±0.5 kg) were studied before and after an infusion of either placebo (PL; n=7) or lactic acid (LA; n=7) at a mean dose of 19±4 mM/kg/h. The dose of LA was titrated to induce a progressive metabolic acidosis to achieve a base excess of -8 to -12 mEq/L in 120 min and to maintain an additional 60 min of steady state acidosis. Minute ventilation (V_E), arterial blood pressure (ABP), arterial blood gases (ABG) and CNS glutamate levels were measured during normoxia (RA) and 15 min of hypoxia (FiO₂=0.10). Extracellular GLU 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. (See table).

Table 1 Mean±SE; *p<0.05 (Pre vs Post); #p<0.05 (PL vs LA)

A significant increase in basal V_E was observed post- LA infusion but the ventilatory response to hypoxia was markedly attenuated (p<0.05). A significant decrease in NTS GLU levels with hypoxia was noted post-LA infusion(p<0.05). Changes in V_E and GLU levels during hypoxia were not different pre- and post-PL. Changes in ABP, HR, PaO₂ and PaCO₂ during hypoxia were not significantly different pre- and post-PL or LA. These results suggest that the attenuation in the ventilatory response to hypoxia observed during LA-induced metabolic acidosis in newborn piglets is in part modulated by a decrease in the CNS glutamatergic activity.