OBJECTIVE: Free radical-induced postasphyxial reperfusion injury has been 
recognized as an important cause of brain tissue damage. We investigated the 
effect of high-dose allopurinol (ALLO; 40 mg/kg), a xanthine-oxidase inhibitor 
and free radical scavenger, on free radical status in severely asphyxiated 
newborns and on postasphyxial cerebral perfusion and electrical brain activity.
METHODS: Free radical status was assessed by serial plasma determination of 
nonprotein-bound iron (microM), antioxidative capacity, and malondialdehyde 
(MDA; microM). Cerebral perfusion was investigated by monitoring changes in 
cerebral blood volume (delta CBV; mL/100 g brain tissue) with near infrared 
spectroscopy; electrocortical brain activity (ECBA) was assessed in microvolts 
by cerebral function monitor. Eleven infants received 40 mg/kg ALLO 
intravenously, and 11 infants served as controls (CONT). Plasma nonprotein-bound 
iron, antioxidative capacity, and MDA were measured before 4 hours, between 16 
and 20 hours, and at the second and third days of age. Changes in CBV and ECBA 
were monitored between 4 and 8, 16 and 20, 58 and 62, and 104 and 110 hours of 
age.
RESULTS: Six CONT and two ALLO infants died after neurologic deterioration. No 
toxic side effects of ALLO were detected. Nonprotein-bound iron (mean +/- SEM) 
in the CONT group showed an initial rise (18.7 +/- 4.6 microM to 21.3 +/- 3.4 
microM) but dropped to 7.4 +/- 3.5 microM at day 3; in the ALLO group it dropped 
from 15.5 +/- 4.6 microM to 0 microM at day 3. Uric acid was significantly lower 
in ALLO-treated infants from 16 hours of life on. MDA remained stable in the 
ALLO group, but increased in the CONT group at 8 to 16 hours versus < 4 hours 
(mean +/- SEM; 0.83 +/- 0.31 microM vs 0.50 +/- 0.14 microM). During 4 to 8 
hours, delta CBV-CONT showed a larger drop than delta CBV-ALLO from baseline. 
During the subsequent registrations CBV remained stable in both groups. 
ECBA-CONT decreased, but ECBA-ALLO remained stable during 4 to 8 hours of age. 
Neonates who died had the largest drops in CBV and ECBA.
CONCLUSION: This study suggests a beneficial effect of ALLO treatment on free 
radical formation, CBV, and electrical brain activity, without toxic side 
effects.