Effect of hypoxia/hypercapnia on metabolism of 6-[(18)F]fluoro-L-DOPA in newborn piglets.
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).
Bauer
Reinhard
R
Institute of Pathophysiology, Friedrich Schiller University, D-07740 Jena, Germany. rbau@mti-n.mti.uni-jena.de
Brust
Peter
P
Walter
Bernd
B
Vorwieger
Gerd
G
Bergmann
Ralf
R
Elhalag
Elsayed
E
Fritz
Anne
A
Steinbach
Jörg
J
Füchtner
Frank
F
Hinz
Rainer
R
Zwiener
Ulrich
U
Johannsen
Bernd
B
D000818:Animals; D000831:Animals, Newborn; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D001238:Asphyxia Neonatorum / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000503:physiopathology; D001921:Brain / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000503:physiopathology; D002320:Cardiovascular Physiological Phenomena; D002560:Cerebrovascular Circulation / Q000502:physiology; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics*; D004298:Dopamine / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D006801:Humans; D006935:Hypercapnia / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000503:physiopathology; D007231:Infant, Newborn; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology; D013552:Swine; D014055:Tomography, Emission-Computed
C043437:fluorodopa F 18; D019344:Lactic Acid; D004295:Dihydroxyphenylalanine; D001142:Aromatic-L-Amino-Acid Decarboxylases; D010100:Oxygen; D004298:Dopamine