EFFECT OF DICHLOROACETATE ON PA-CO2 RESPONSES TO HYPOXIA IN AWAKE GOATS

To gain insight into the role of cerebral lactic acidosis in the hypox ic ventilatory response, we administered dichloroacetate (DCA) intrave nously to inhibit lactic acid production in 7 awake goats (40-70 kg) d uring 0.5 h of normoxia (inspired O-2 fraction = 0.209) and 5 h of poi kilocapnic hypoxia (inspired O-2 fraction = 0.125). On separate days, these goats were also studied with a continuous saline infusion (18 ml /h iv) during 5 h of normoxia and hypoxia. Arterial PCO2, (Pa-CO2) did not change during the 5-h normoxic period. During hypoxia, arterial P O2 fell significantly (P < 0.05) with both saline (from 111.3 to 39.0 Torr) and DCA(from 111.8 to 42.0 Torr) infusions. Pa-CO2 decreased (P < 0.05) during the first 0.5 h of both the saline and DCA hypoxia prot ocols. The decrease was greater (P < 0.05) during DCA (from 36.5 to 33 .5 Torr) than during saline infusion (from 37.7 to 36.3 Torr). With sa line infusion, Pa-CO2 decreased (P < 0.05) by 4.9 Torr between 0.5 and 5.0 h of hypoxia. However, over this period of DCA hypoxia, Pa-CO2 di d not significantly decrease (P > 0.05). We conclude that the enhanced hyperventilation with DCA during acute hypoxia is consistent with bra in lactic acidosis depressing breathing. Absence of additional signifi cant hyperventilation after 0.5 h of DCA hypoxia suggests that a time- dependent alleviation of brain lactic acidosis might normally contribu te to ventilatory acclimatization to hypoxia.