Effect of hypoxia/hypercapnia on metabolism of 6-[¹⁸F]fluoro-L-DOPA in newborn piglets

There is evidence that the dopaminergic system is sensitive to altered p_O2 in the immature brain. However, the respective enzyme activities have not been measured in the living neonatal brain together with brain oxidative metabolism. Therefore ¹⁸F-labelled 6-fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) together with positron emission tomography (PET) was used to estimate the activity of the aromatic amino acid decarboxylase (AADC) in the brain of fifteen newborn piglets (2 - 5 days old). Two PET scans were performed in each piglet. Eleven animals underwent a period of normoxia and moderate hypoxia/hypercapnia (H/H). The remaining four animals were used as an untreated control group. Simultaneously, the brain tissue p_O2 was recorded, the regional cerebral blood flow (CBF) was measured with colored microspheres and the cerebral metabolic rate of oxygen (CMRO₂) was determined. In addition, in four untreated and six H/H treated piglets the relative amounts of fluorodopamine and the respective metabolites were determined in brain tissue samples using HPLC analysis. H/H conditions were induced by lowering the inspired fraction of oxygen from 0.35 to 0.10 and adding CO₂ to the inspired gas resulting in an arterial p_O2 between 74 and 79 mmHg. H/H elicited a more than 3-fold increase of the CBF(P < 0.05) so that CMRO₂ remained unchanged throughout the H/H period. Despite this, the brain tissue p_O2 was reduced from 19 ± 4 to 6 ± 3 mmHg /P < 0.05). The permeability-surface area product of FDOPA (PS^FDOPA) was unchanged. However, the transfer rate of FDOPA (k₃ ^FDOPA of the nigrostriatal dopaminergic system and the relative amounts of fluorodopamine and the respective metabolites were significantly increased (P < 0.05). It is suggested that H/H induces an increase of AADC activity. However, an H/H-induced CBF increase maintains bulk O₂ delivery and preserves CMRO₂.