DECREASED ENERGY-METABOLISM IN BRAIN-STEM DURING CENTRAL RESPIRATORY DEPRESSION IN RESPONSE TO HYPOXIA

Metabolic changes in the brain stem were measured at the time when oxy gen deprivation-induced respiratory depression occurred. Eucapnic vent ilation with 8% oxygen in vagotomized urethan-anesthetized rats result ed in cessation of respiratory drive, monitored by recording diaphragm electromyographic activity, on average within II min (range 5-27 min) , presumably via central depressant mechanisms. At that time, the brai n stems were frozen in situ for metabolic analyses. By using 20-mu m l yophilized sections from frozen-fixed brain stem, microregional analys es of ATP, phosphocreatine, lactate, and intracellular pH were made fr om 1) the ventral portion of the nucleus gigantocellularis and the par apyramidal nucleus; 2) the compact and ventral portions of the nucleus ambiguus; 3) midline neurons; 4) nucleus tractus solitarii; and 5) th e spinal trigeminal nucleus. At the time of respiratory depression, la ctate was elevated threefold in all regions. Both ATP and phosphocreat ine were decreased to 50 and 25% of control, respectively. Intracellul ar pH was more acidic by 0.2-0.4 unit in these regions but was relativ ely preserved in the chemosensitive regions near the ventral and dorsa l medullary surfaces. These results show that hypoxia-induced respirat ory depression was accompanied by metabolic changes within brain stem regions involved in respiratory and cardiovascular control. Thus it ap pears that there was significant energy deficiency in the brain stem a fter hypoxia-induced respiratory depression had occurred.