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 (³¹P MRS) assessed associations between changes in the oxidation state of cerebral mitochondrial cytochrome-c-oxidase (δ[_oxCCO]) and ³¹P metabolite peak-area ratios during and after transient cerebral hypoxia-ischemia (HI) in the newborn piglet. Methods: Twenty-four piglets (aged<24h) underwent transient HI (inspired oxygen fraction 9% and bilateral carotid artery occlusion for ~20min). Whole-brain ³¹P MRS and NIRS data were acquired every minute. Inorganic phosphate (Pi)/epp, phosphocreatine (PCr)/epp, and total nucleotide triphosphate (NTP)/epp were measured by ³¹P MRS and were plotted against δ[_oxCCO] during HI and recovery (epp=exchangeable phosphate pool=Pi+PCr+2γ-NTP+β-NTP). Results: During HI δ[_oxCCO], PCr/epp and NTP/epp declined and Pi/epp increased. Significant correlations were seen between ³¹P ratios and δ[_oxCCO]; during HI a threshold point was identified where the relationship between δ[_oxCCO] and both NTP/epp and Pi/epp changed significantly. Outcome at 48h related to recovery of δ[_oxCCO] and ³¹P ratios 1h post-HI (survived: 1-h NTP/epp 0.22±0.02, δ[_oxCCO] -0.29±0.50μM; died: 1-h NTP/epp 0.10±0.04, δ[_oxCCO] -2.41±1.48μM). Conclusions: Both lowered δ[_oxCCO] and NTP/epp 1h post-HI indicated mitochondrial impairment. Animals dying before 48h had slower recovery of both δ[_oxCCO] and ³¹P ratios by 1h after HI.