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 ((31)P MRS) assessed associations between changes in the oxidation state of cerebral mitochondrial cytochrome-c-oxidase (Δ[(ox)CCO]) and (31)P 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 ~ 20 min). Whole-brain (31)P MRS and NIRS data were acquired every minute. Inorganic phosphate (Pi)/epp, phosphocreatine (PCr)/epp, and total nucleotide triphosphate (NTP)/epp were measured by (31)P MRS and were plotted against Δ[(ox)CCO] during HI and recovery (epp = exchangeable phosphate pool = Pi + PCr + 2γ-NTP + β-NTP). RESULTS: During HI Δ[(ox)CCO], PCr/epp and NTP/epp declined and Pi/epp increased. Significant correlations were seen between (31)P ratios and Δ[(ox)CCO]; during HI a threshold point was identified where the relationship between Δ[(ox)CCO] and both NTP/epp and Pi/epp changed significantly. Outcome at 48 h related to recovery of Δ[(ox)CCO] and (31)P ratios 1 h post-HI (survived: 1-h NTP/epp 0.22 ± 0.02, Δ[(ox)CCO] − 0.29 ± 0.50 μM; died: 1-h NTP/epp 0.10 ± 0.04, Δ[(ox)CCO] − 2.41 ± 1.48 μM). CONCLUSIONS: Both lowered Δ[(ox)CCO] and NTP/epp 1 h post-HI indicated mitochondrial impairment. Animals dying before 48 h had slower recovery of both Δ[(ox)CCO] and (31)P ratios by 1 h after HI.