Post hypoxic-ischemic (HI) reperfusion induces brain injury by excess production of free radicals and is characterized by cerebral hypoperfusion, a decreased O2 consumption (CMRO2) and electrocortical brain activity (ECBA). Reduction of free radicals may attenuate this damage. Severe HI (30 min ventilation with 6-7% O2 and 10% CO2 followed by 5 min hypotension) was produced in 5 groups of 7 newborn lambs each. Post HI changes (%) from pre-HI values at 15, 60, 120 and 180 min were measured in carotid artery flow (Qcar[ml/min]), CMRO2 and ECBA[μV]. Immediately after completion of HI the lambs received respectively a placebo (CONT), 0.3 mg/kg/iv Indomethacine (INDO) to inhibit superoxide production (cyclooxygenase pathway), 20 mg/kg/iv Allopurinol (ALLO) to inhibit superoxide production(xanthine oxidase), 2.5 mg/kg/iv Deferoxamine to chelate free iron (DFO) or a combination of these three drugs (COMB).

Results: Qcar decreased up to 50% in CONT at 120, 180 min post HI(p<0.05), remained stable in INDO and ALLO, but increased in DFO and COMB at 180 min post HI vs pre HI (p<0.05). CMRO2 decreased up to 45% in CONT (p<0.05) at 60 min post HI without recovery, remained stable in DFO and INDO, but was significantly higher in ALLO and COMB at 120 and 180 min post HI vs pre HI (p<0.05). ECBA was significantly lower in CONT during the whole post HI (p<0.05) without recovery, INDO and COMB were significantly decreased vs pre HI at 60 and 120 min post HI (p<0.05), but recovered. ECBA in DFO and ALLO remained stable during the post HI period.

Conclusions: Preservation of brain perfusion and metabolism, and recovery of ECBA occurred after treatment with INDO, ALLO and DFO suggesting reduction of reperfusion injury. Combination of these drugs does not seem to have an additional positive effect.