Cerebral Metabolism Measured Using Proton and Phosphorous Magnetic Resonance Spectroscopy (MRS) Following Hypoxia Ischemia (HI) and Administration of Allopurinol (ALLO) and Deferoxamine (DFO)

Abstract 2037

Free radical-induced hypoxic-ischemic (HI) brain injury is characterized by a sudden and late fall in PCr/Pi ratio and an increment in Lac/NAA ratio. We hypothesized that ALLO (xanthine oxidase inhibitor; 20 mg/kg/iv; n=4) and DFO (iron chelator; 10 mg/kg/iv; n=4) reduced the secondary energy failure observed following cerebral HI compared to placebo treated piglets (PLAC; n=4). Severe HI was induced in 12 piglets (1-3 days old) by occluding the common carotid arteries during 1 h combined with a reduction of FiO₂ until PCr/Pi decreased at least 75% from baseline values. Cerebral metabolism was measured in a 4.7 T NMR Spectrometer using proton and phosphorous MRS. Examinations were performed at normoxia, during HI and 2 hrs of reperfusion and were repeated at 24 hrs. PCr/Pi ratios, pHi and Lac/NAA ratios were calculated.

Results: 3 piglets died (2 in PLAC and 1 in DFO at resp. 5, 9, and 13 h post-HI). For both proton and phosphorous NMR results from normoxia to 24 h post HI, see figure.

Fig 1

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Conclusion: ALLO prevented a fall in PCr/Pi ratio at 24 h post-HI. Both ALLO and DFO prevented increment of Lac/NAA at 24 hours after HI. We suggest that ALLO and DFO reduce post HI brain injury by preventing free radical-induced brain tissue damage.