RELATIONSHIPS OF DOPAMINE, CORTICAL OXYGEN-PRESSURE, AND HYDROXYL RADICALS IN BRAIN OF NEWBORN PIGLETS DURING HYPOXIA AND POSTHYPOXIC RECOVERY

The present study describes the relationships of extracellular striata l dopamine, cortical oxygen pressure, and striatal hydroxyl radicals i n brain of newborn piglets during hypoxia and posthypoxic reoxygenatio n. Hypoxia was induced by reducing the fraction of inspired oxygen (Fi O2) from 22% (control) to 7% for 1 h. The FiO2 was then returned to th e control value and measurements were continued for 2 h. Cerebral oxyg en pressure was measured by the oxygen dependent quenching of phosphor escence and extracellular levels of dopamine, 3,4-dihydroxyphenylaceti c acid (DOPAC), homovanillic acid (HVA), and hydroxy radicals in the s triatum were determined by in vivo microdialysis. Hypoxia decreased th e cortical oxygen pressure from 47 +/- 2 to 9 +/- 1.3 torr (p < 0.001) ; the levels of extracellular dopamine in the striatum increased to 16 ,000 +/- 3,270% of control (p < 0.01), whereas the levels of DOPAC and HVA decreased to 25.3 +/- 6% (p < 0.001) and 36 +/- 5% (p < 0.01) of control, respectively. Compared with control, the hydroxyl radical lev els at each time point were not significantly increased during hypoxia , although the sum of the measured values was significantly increased (p < 0.05). During the first 5 min after FiO2 was returned to 22%, the cortical oxygen pressure increased to control values and stayed at th is level for the remainder of the measurement period. The extracellula r level of dopamine declined to values not statistically different fro m control during 40 min of reoxygenation. During the first 10 min of r eoxygenation, DOPAC and HVA further decreased and then began to slowly increase. By 70 min of reoxygenation, the values were not significant ly different from control. Hydroxyl radicals were above control during the entire period of reoxygenation, with maximal values observed afte r 100 min of reoxygenation. This increase was largely abolished by inj ecting the animals with alpha-methyl-p-tyrosine 5 h before hypoxia, a procedure that depleted the brain of dopamine. Our results suggest tha t oxidation of striatal dopamine during posthypoxic reoxygenation is a t least partly responsible for the observed increase in striatal level of hydroxyl radicals that may exacerbate posthypoxic cerebral injury.