Effect of dichloroacetate on PaCO2 responses to hypoxia in awake goats.
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.
Aaron
E A
EA
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Forster
H V
HV
Lowry
T F
TF
Korducki
M J
MJ
Ohtake
P J
PJ
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
D002245:Carbon Dioxide; D003999:Dichloroacetic Acid