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

• Published in: Brain research Vol. 934; no. 1; pp. 23 - 33
• Main Authors: Bauer, Reinhard, Brust, Peter, Walter, Bernd, Vorwieger, Gerd, Bergmann, Ralf, Elhalag, Elsayed, Fritz, Anne, Steinbach, Jörg, Füchtner, Frank, Hinz, Rainer, Zwiener, Ulrich, Johannsen, Bernd
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 26.04.2002; Amsterdam Elsevier; New York, NY
• Subjects: Animals; Animals, Newborn; Aromatic amino acid decarboxylase; Aromatic-L-Amino-Acid Decarboxylases - metabolism; Asphyxia Neonatorum - diagnostic imaging; Asphyxia Neonatorum - enzymology; Asphyxia Neonatorum - physiopathology; Biochemistry and metabolism; Biological and medical sciences; Brain - diagnostic imaging; Brain - enzymology; Brain - physiopathology; Cardiovascular Physiological Phenomena; Central nervous system; Cerebrovascular Circulation - physiology; Colored microsphere; Dihydroxyphenylalanine - analogs & derivatives; Dihydroxyphenylalanine - metabolism; Dihydroxyphenylalanine - pharmacokinetics; Dopamine - metabolism; Energy Metabolism - physiology; FDOPA; Fundamental and applied biological sciences. Psychology; Humans; Hypercapnia - diagnostic imaging; Hypercapnia - enzymology; Hypercapnia - physiopathology; Hypoxia-Ischemia, Brain - diagnostic imaging; Hypoxia-Ischemia, Brain - enzymology; Hypoxia-Ischemia, Brain - physiopathology; Infant, Newborn; Lactic Acid - metabolism; Male; Metabolic Clearance Rate - physiology; Newborn piglet; Oxygen - metabolism; Oxygen Consumption - physiology; Positron emission tomography; Swine; Tomography, Emission-Computed; Vertebrates: nervous system and sense organs; Dopamine metabolism; Colored microsphere; Newborn piglet; Aromatic amino acid decarboxylase; Neurotransmitters, modulators, transporters and receptors; FDOPA; Positron emission tomography; Oxygen; Enzyme; Environmental factor; Lyases; Metabolism; Pig; Hypercapnia; Carbon-carbon lyases; Vertebrata; Mammalia; Enzymatic activity; Carboxy-lyases; Newborn animal; Aromatic-L-amino-acid decarboxylase; Hypoxia; Artiodactyla; Dopa; Ungulata; Emission tomography
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(02)02315-6

There is evidence that the dopaminergic system is sensitive to altered p O 2 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 O 2 was recorded, the regional cerebral blood flow (CBF) was measured with colored microspheres and the cerebral metabolic rate of oxygen (CMRO 2) 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 CO 2 to the inspired gas resulting in an arterial p CO 2 between 74 and 79 mmHg. H/H elicited a more than 3-fold increase of the CBF ( P<0.05) so that the CMRO 2 remained unchanged throughout the H/H period. Despite this, the brain tissue p O 2 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 ( k 3 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 O 2 delivery and preserves CMRO 2.