Brain mitochondrial oxidative metabolism during and after cerebral hypoxia-ischemia studied by simultaneous phosphorus magnetic-resonance and broadband near-infrared spectroscopy

Background: Multimodal measurements combining broadband near-infrared spectroscopy (NIRS) and phosphorus magnetic resonance spectroscopy (P-31 MRS) assessed associations between changes in the oxidation state of cerebral mitochondrial cytochrome-c-oxidase (Delta[oxCCO]) and P-31 metabolite peak-area ratios during and after transient cerebral hypoxia-ischemia (HI) in the newborn piglet. Methods: Twenty-four piglets (aged < 24 h) underwent transient HI (inspired oxygen fraction 9% and bilateral carotid artery occlusion for similar to 20 min). Whole-brain P-31 MRS and NIRS data were acquired every minute. Inorganic phosphate (Pi)/epp, phosphocreatine (PCr)/epp, and total nucleotide triphosphate (NTP)/epp were measured by P-31 MRS and were plotted against.[oxCCO] during HI and recovery (epp = exchangeable phosphate pool = Pi + PCr + 2 gamma-NTP + beta-NTP). Results: During HI.[oxCCO], PCr/epp and NTP/epp declined and Pi/epp increased. Significant correlations were seen between 31P ratios and.[oxCCO]; during HI a threshold point was identified where the relationship between Delta[oxCCO] and both NTP/epp and Pi/epp changed significantly. Outcome at 48 h related to recovery of Delta[oxCCO] and P-31 ratios 1 h post-HI (survived: 1-h NTP/epp 0.22 + 0.02, Delta[oxCCO] -0.29 +/- 0.50 mu M; died: 1-h NTP/epp 0.10 +/- 0.04, Delta[oxCCO] -2.41 +/- 1.48 mu M). Conclusions: Both lowered Delta[oxCCO] and NTP/epp 1 h post-HI indicated mitochondrial impairment. Animals dying before 48 h had slower recovery of both Delta[oxCCO] and P-31 ratios by 1 h after HI. (C) 2013 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/3.0/).