The present studies describes the relationship between extracellular dopamine in striatum of newborn piglets and cortical oxygen pressure. The extracellular level of dopamine was measured by in vivo microdialysis and the oxygen pressure in the cortex was measured by phosphorescence lifetime of oxygen probe in the blood. Controlled, graded levels of hypoxic insult to the brain of animals were generated by decreasing of the oxygen fraction in the inspired gas (FiO2) from 21% to 14%, 11%, and 9%. This resulted in decrease in the cortical oxygen pressure from 31-35 Torr to about 24 Torr, 15 Torr and 4 Torr, respectively. The changes in extracellular level of dopamine, DOPAC and HVA were dependent on changes in cortical oxygen pressure. Stepwise decrease in the cortical oxygen pressure (see above) caused increases in extracellular dopamine of about 80%, 200% and 550%, respectively. The levels of DOPAC and HVA progressively decreased and when cortical oxygen decreased to 4-6 Torr were about 50% and 70% of control, respectively. After return of FiO2 to control (21%), the cortical oxygen pressure rapidly increased to above normal, then returned to control values. The extracellular levels of dopamine, DOPAC, and HVA recovered more slowly, attaining control values in about 30 minutes. The data show that extracellular levels of dopamine increase with even very small decreases in oxygen pressure. Thus, there is no "oxygen reserve" which protects dopamine release and metabolism from decrease in oxygen pressure.

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The present study tests the hypothesis that ventilation with 100% 02 during recovery from asphyxia leads to greater disturbance in brain function, as measured by dopamine metabolism, than does ventilation with 21 % oxygen . This hypothesis was tested using mechanically ventilated, anesthetized newborn piglets as an animal model . Cortical oxygen pressure was measured by the oxygen-dependent quenching of phosphorescence, striatal blood flow by laser Doppler, and the extracellular levels of dopamine and its metabolites by in vivo microdialysis . After establishment of a baseline, both the fraction of inspired oxygen (Fi0 2) and the ventilator rate were reduced in a stepwise fashion every 20 min over a 1-h period . For the subsequent 2-h recovery, the animals were randomized to breathing 21 or 100% oxygen . It was observed that during asphyxia cortical oxygen pressure decreased from 36 to 7 torr, extracellular dopamine increased 8,300%, and dihydroxyphenylacetic acid and homovanillic acid decreased by 65 and 60%, respectively, compared with controls . During reoxygenation after asphyxia, cortical oxygen pressure was significantly higher in the piglets ventilated with 100% oxygen than in those ventilated with 21 % oxygen (19 vs . 11 torr) . During the first hour of reoxygenation, extracellular dopamine levels decreased to -200% of control in the 21 % oxygen group, whereas these levels were still much higher in the 100% oxygen group (-500% of control) . After -2 h of reoxygenation, there was a secondary increase in extracellular dopamine to -750 and -3,000% of baseline for the animals ventilated with 21 and 100%, respectively . It is concluded that although 100% Fi02 after asphyxia increases cortical oxygenation compared with 21 % Fi02, it also results in poorer recovery in dopamine metabolism and higher secondary release of striatal dopamine . The resulting increased extracellular levels of dopamine may exacerbate posthypoxic cerebral injury . Key Words: Hypoxia-Hyperoxia-Dopamine-Brain -Newborn . J. Neurochem. 64, 292-298 (1995) .Hyperoxia is currently one of the most effective treatments for decreased pulmonary arterial pressure 292

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The effect of graded hypoxia induced by hyperventilation on the activity of tyrosine hydroxylase was measured in vivo by microdialysis. Microdialysis probes were inserted into the striatum of newborn piglets and perfused with medium containing 3-hydroxybenzylhydrazine, an inhibitor of L-aromatic amino acid decarboxylase. The level of 3,4-dihydroxyphenylalanine (DOPA) measured in the effluent dialysate was then an index of tyrosine hydroxylase activity. The oxygen pressure in the veins and capillaries of the cortex was measured, through a cranial window placed over the parietal cortex, by the phosphorescence lifetime of palladium-meso-tetra(4-carboxyphenyl)porphine added to the blood. After baseline measurements, PaCO2 was decreased from 38 torr (control value) to 19, 13, and 11 torr resulting in decreases in the cortical oxygen pressure from 40 +/- 6 torr to 26 +/- 3, 23 +/- 4, and 20 +/- 4 torr, respectively. Decrease in the oxygen pressure to 26 +/- 3 torr caused a statistically significant increase of 25-30% in the level of DOPA in the effluent perfusate. During the next step of increase in ventilator rate, when oxygen decreased only slightly, the level of DOPA remained at the higher level. Ventilation rates that lowered the oxygen pressure to below 20 torr, however, caused a progressive decrease in the level of DOPA. During recovery, the level of DOPA steadily increased, attaining 160% of control value after 1.5 h. When the oxygen pressure was decreased to 16 +/- 2 torr by a single increase in ventilator rate, the DOPA level decreased in the effluent to 15-20% below control.(ABSTRACT TRUNCATED AT 250 WORDS)

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