DEFEROXAMINE (DFO) REDUCES CEREBRAL REPERFUSION INJURY AFTER BIRTH ASPHYXIA.• 2267

Abstract

Non-protein-bound iron (NPBI) can convert hydrogen peroxide into highly reactive hydroxyl radicals and has been associated with post hypoxic-ischemic(HI) reperfusion injury of the brain. This type of injury is characterized by post-HI cerebral hypoperfusion, and decreased cerebral O2-consumption(CMRo2) and electrocortical brain activity (ECBA). We investigated if the iron chelator DFO could reduce reperfusion injury. Severe HI was induced in 12 newborn lambs and changes from pre-HI values were measured for brain blood flow (carotid flow [mL/min]; Qcar), CMRo2 and ECBA [uV] at 15, 60, 120 and 180 min after HI. Immediately after completion of HI 6 lambs received a placebo (CONT) and 6 DFO (10 mg/kg/iv). Results: CONT showed a significant decrease in Qcar (120, 180 min), CMRo2 (60,180 min) and ECBA (15-180 min) up to 60% of pre-HI levels without recovery to pre-HI-levels. In contrast, the DFO-lambs had a preservation of post-HI Qcar, CMRo2 and ECBA with significantly higher values as compared to CONT lambs (see figure). Conclusions: Preservation of post-HI cerebral perfusion, CMRo2 and ECBA in DFO-lambs suggests that chelation of NPBI with DFO, immediately after HI, prevents post-asphyxial cerebral reperfusion injury.