Effect of dichloroacetate on paco2 responses to hypoxia in awake
goats.
Aaron, E. A., H. V. Forster, T. F. Lowry, M. J. Korducki, and P. J.
Ohtake.
Dept. of Physiology, Medical College of WI and Zablocki VA,
Milwaukee, WI 53226, USA
APStracts 2:0362A, 1995.
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 hours of normoxia (Fio2 = 0.209) and 5 hours of
poikilocapnic hypoxia (Fio2 = 0.125). On separate days, these goats
were also studied with a continuous saline infusion (IV, 18 ml x hr
-1) during 5 hours of normoxia and hypoxia. Paco2 did not change
during the 5 hour normoxic period. During hypoxia, Pao2 fell
significantly (p<.05) with both saline (111.3 to 39.0 mmHg) and
DCA (111.8 to 42.0 mmHg) infusion. Paco2 decreased (p<.05)
during the first 0.5 hour of both the saline and DCA hypoxia
protocols. The decrease was greater (p<.05) during DCA (36.5 to
33.5 mmHg) than during saline infusion (37.7 to 36.3 mmHg). With
saline infusion Paco2 decreased (p<.05) 4.9 mmHg between 0.5 and
5.0 hours of hypoxia. However, over this period of DCA hypoxia, Paco2
did not significantly decrease (p>.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 hrs of DCA hypoxia
suggests that a time dependent alleviation of brain lactic acidosis
might normally contribute to ventilatory acclimatization to hypoxia.
Received 27 October 1994; accepted in final form 9 August 1995.
APS Manuscript Number A1106-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 24 August 1995.