Decreased energy metabolism in brainstem during central respiratory
depression in response to hypoxia.
Lamanna, J. C., M. A. Haxhiu, K. L. Kutina-Nelson, S. Pundik, B.
Erokwu, E. R. Yeh, W. D. Lust, and N. S. Cherniack.
School of Medicine, Case Western Reserve University, Cleveland OH
44106
APStracts 3:0282A, 1996.
Metabolic changes in the brainstem were measured at the time when
oxygen deprivation induced respiratory depression occurred. Eucapnic
ventilation with 8% oxygen in vagotomized, urethane anesthetized rats
resulted in cessation of respiratory drive, monitored by recording
diaphragm electromyographic activity, on average within 11 minutes
(range 5 - 27) presumably via central depressant mechanisms. At that
time, the brainstems were frozen in situ for metabolic analyses. From
20 micron lyophilized sections from frozen-fixed brainstem,
microregional analyses of ATP, PCr, lactate and pHi were made from a)
the ventral portion of the nucleus gigantocellularis and the
parapyramidal nucleus; b) the compact and ventral portions of the
nucleus ambiguus; c) midline neurons; d) nucleus tractus solitarius;
and e) the spinal trigeminal nucleus. At the time of respiratory
depression, lactate was elevated in all regions by threefold. Both
ATP and PCr were decreased to half and 25 percent of control,
respectively. Intracellular pHi was more acidic by 0.2 to 0.4 units
in these regions, but was relatively preserved in the chemosensitive
regions near the ventral and dorsal meduallary surfaces. These
results show that hypoxia-induced respiratory depression was
accompanied by metabolic changes within brainstem regions involved in
respiratory and cardiovascular control. Thus, it appears that there
was significant energy deficiency in the brainstem after hypoxia
-induced respiratory depression had occurred.
Received 2 January 1996; accepted in final form 29 May 1996.
APS Manuscript Number A7-6.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96