Free radical-induced postasphyxial reperfusion injury has been recognized as an important cause for brain tissue damage. We investigated the effect of ALLO, a xanthine-oxidase inhibitor and free radical scavenger, on changes of cerebral blood volume (▵CBV; mL/100g brain tissue) and cellular oxygenation (▵Cytaa3; μmol/L) using near infrared spectroscopy, electrocortical brain activity (ECBA; μV) and the status of prooxidants(non-protein-bound iron [NPBI;μM]), antioxidants (reduced/oxidized vitamin C-ratio [VCred/ox]) and lipid peroxidation (malondialdehyde [MDA;μM]) in 20 severely asphyxiated neonates. 9 Babies received ALLO (40 mg/kg iv: 20 mg/kg before 4h of age, followed by 20 mg/kg 12h after 1st dose), 11 babies served as controls (CONT). ▵CBV, ▵Cytaa3 and ECBA were monitored between 4-8h, 16-20h, 58-62h and 104-110h of age; and plasma NPBI, VCred/ox and MDA measured.

Results: 5/11 CONT and 2/9 ALLO died after neurological deterioration. During 4-8h CBV-CONT showed a larger drop than CBV-ALLO from baseline (mean±SEM: -0.69±0.46 vs. -0.19±0.15 mL/100g). Cytaa3-CONT tended to drop and Cyta3-ALLO to increase during 4-8h(-0.42±0.49 vs. +0.45±0.28 μmol/L). During the subsequent registrations CBV and Cytaa3 remained stable in both groups. ECBA-CONT dropped during 4-8h (12±1 to 8±2 μV;p<0.05), afterwards ECBA recovered in CONT (range: 12-14 μV). ECBA-ALLO remained stable during the study period (range: 12-15 μV). Neonates who died had the largest drops in CBV and ECBA. NPBI-CONT increased from 9.8±4.7 (4-8h) to 36.7±2.3 (16-20h; p<0.05), but dropped to 5.0±6.2 μM(100-104h). NPBI-ALLO dropped from 31.9±8 (4-8h) to 0 μM (100-106h; p<0.05). VCred/ox-CONT and VCred/ox-ALLO showed a non significant drop and rise respectively. MDA showed a small increase in CONT, but remained stable in ALLO.

Conclusions: The results so far suggest a beneficial effect of early neonatal ALLO-treatment on postasphyxial reperfusion injury of the brain, as indicated by preservation of neonatal cerebral perfusion and electrical brain activity, and a more favorable redox status.