title: Effect of dichloroacetate on PaCO2 responses to hypoxia in awake goats.
abstract: To gain insight into the role of cerebral lactic acidosis in the hypoxic ventilatory response, we administered dichloroacetate (DCA) intravenously to inhibit lactic acid production in 7 awake goats (40-70 kg) during 0.5 h of normoxia (inspired O2 fraction = 0.209) and 5 h of poikilocapnic hypoxia (inspired O2 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 (PaCO2) did not change during the 5-h normoxic period. During hypoxia, arterial PO2 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. PaCO2 decreased (P < 0.05) during the first 0.5 h of both the saline and DCA hypoxia protocols. 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 saline infusion, PaCO2 decreased (P < 0.05) by 4.9 Torr between 0.5 and 5.0 h of hypoxia. However, over this period of DCA hypoxia, PaCO2 did not significantly decrease (P > 0.05). We conclude that the enhanced hyperventilation with DCA during acute hypoxia is consistent with brain lactic acidosis depressing breathing. Absence of additional significant hyperventilation after 0.5 h of DCA hypoxia suggests that a time-dependent alleviation of brain lactic acidosis might normally contribute to ventilatory acclimatization to hypoxia.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Aaron
authors.forename: H V
authors.initials: HV
authors.lastname: Forster
authors.forename: T F
authors.initials: TF
authors.lastname: Lowry
authors.forename: M J
authors.initials: MJ
authors.lastname: Korducki
authors.forename: P J
authors.initials: PJ
authors.lastname: Ohtake
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood*; D002628:Chemoreceptor Cells / Q000187:drug effects; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D005260:Female; D006041:Goats; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000097:blood* / Q000503:physiopathology; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology; D014851:Wakefulness / Q000502:physiology
chemical_list: D002245:Carbon Dioxide; D003999:Dichloroacetic Acid