Extracellular increase of hypoxanthine and xanthine in the cortex and basal ganglia of fetal lambs during hypoxia-ischemia.
A microdialysis procedure was used to sample purine catabolites from the extracellular compartment of two areas of the fetal brain, the cerebral cortex and the striatum region. Seven exteriorized, anesthetized fetal sheep were studied during conditions of normal oxygenation and during asphyxia induced by stepwise lowering of maternal placental perfusion pressure. Fetal cerebral blood flow (CBF) was measured with the 133Xe washout method. Somatosensory evoked potentials were recorded during tactile stimulation of the fetal snout. The purine catabolites hypoxanthine (HX), xanthine (Xan), guanosine (Gua), inosine (Ino) and adenosine (Ade) were measured in arterial and venous plasma and in the dialysate by a HPLC method. During gradually increasing asphyxia HX increased 4-6-fold both in cerebral tissue and in arterial plasma, while Xan rose 1.5-3 times in cerebral tissue and arterial plasma. Gua did not change in either tissue or blood and Ino did not rise until at the most extreme degree of asphyxia it rose 2-4-fold. Ade concentrations remained unaltered during moderate asphyxia (when CBF rose 3-fold), but demonstrated a significant (2-3-fold) augmentation at the most extreme degrees of asphyxia. The results thus suggests a significant accumulation of oxypurines, especially HX, in the interstitium of the fetal brain during asphyxia. The rise in xanthine concentration demonstrates the presence of an activity of xanthine oxidase in brain tissue. A discrepancy between the elevation of CBF and of the tissue concentration of Ade does not support a direct role of Ade in the asphyctic cerebral vasodilation in the fetus.
Kjellmer
I
I
Department of Pediatrics I, Gothenburg University, Sweden.
Andiné
P
P
Hagberg
H
H
Thiringer
K
K
D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism* / Q000503:physiopathology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000503:physiopathology; D005073:Evoked Potentials, Somatosensory; D005110:Extracellular Space / Q000378:metabolism; D005333:Fetus / Q000378:metabolism*; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D012756:Sheep / Q000378:metabolism* / Q000502:physiology; D019820:Xanthine; D014970:Xanthines / Q000378:metabolism*
D007042:Hypoxanthines; D014970:Xanthines; D019820:Xanthine; D019271:Hypoxanthine