THE EFFECT OF ANTIOXIDATIVE COMBINATION THERAPY ON POST HYPOXIC-ISCHEMIC PERFUSION, METABOLISM, AND ELECTRICAL-ACTIVITY OF THE NEWBORN BRAIN

Reoxygenation and reperfusion after severe hypoxia and ischemia (HI) c ontribute substantially to birth asphyxia-related brain injury. Excess production of free radicals via metabolization of arachidonic acid, x anthine oxidase, and non-protein-bound iron play an important role. Ce rebral reperfusion injury is characterized by a decrease in perfusion, oxygen consumption, and electrical activity of the brain. Reduction o f free radical production may attenuate these features. We therefore i nduced severe HI in 35 newborn lambs, and upon reperfusion the lambs r eceived a placebo [control (CONT), n = 7], the cyclooxygenase inhibito r indomethacin (INDO, 0.3 mg/kg/i.v., n = 7), the xanthine oxidase inh ibitor allopurinol (ALLO, 20 mg/kg/i.v., n = 7), the iron chelator def eroxamine (DFO, 2.5 mg/kg/i.v., n = 7), or a combination of these drug s (COMB, n = 7). In each group changes (%) from pre-HI values were inv estigated for brain perfusion [measured by carotid artery flow (Q(car) , mL/min)], (relative) cerebral O-2, metabolism (CMRO2), and electroco rtical brain activity (ECBA, mu V) at 15, 60, 120, and 180 min post-HI , Q(car), decreased significantly at 120 and 180 min post-HI in CONT ( p < 0.05), but not in INDO, ALLO, DFO, and COMB groups. CMRO2,, decrea sed significantly in CONT at 60 min post-HI (p < 0.05), remained stabl e in DFO and INDO, and was significantly higher in ALLO and COMB (p < 0.05) at 120 and 180 min post-HI. ECBA was significantly lower in CONT during the whole post-HI period (p < 0.05), ECBA in INDO and COMB wer e significantly decreased at 60 and 120 min post-HI (p < 0.05), but re covered afterward, whereas DFO and ALLO remained stable during the pos t-HI period. In conclusion preservation of Q(car) and CMRO2 and recove ry of ECBA occurred after treatment with INDO, ALLO, and DFO; combinat ion of these drugs did not have an additional positive effect.