Abstract
Background: Alanine (Ala), a nonessential amino acid, is present in normal brain at a concentration of ∼0.5 mmol/kg. During acute hypoxia-ischaemia (HI) Ala increases due to decreased flux of pyruvate through the Krebs cycle and the activity of alanine transaminase (AAT). Brain Ala increases in proportion to the severity of HI and may be detected using proton (1H) magnetic resonance spectroscopy (MRS).
Aim: To investigate relationships between the severity of secondary (delayed) energy failure (SEF) and late brain Ala metabolite ratios following transient cerebral HI in the newborn piglet.
Design/Methods: Seven newborn piglets (<24 hrs old) were studied under general anaesthesia (isoflurane & morphine) before, during and for up to 48 hours following transient HI (reversible bilateral carotid occlusion and 12% FiO2 for 45 min). Whole-brain pulse-acquire phosphorus (31P; repetition time (TR) 10 s) and localised 1H (PRESS, thalamic, echo time 270 ms, TR 5 s) MRS data were acquired serially before, during (31P only), and following HI. Spectra were analysed using AMARES (31P) and LCModel (1H).
Results: In two piglets SEF was not observed. In the remaining 5 SEF ranged between mild and severe as quantified by delayed reductions in [phosphocreatine]/[inorganic phosphate] ([PCr]/[Pi]) and [nucleotide triphosphate]/[exchangeable high-energy phosphate pool] ([NTP]/[EPP]) and increases in lactate/total creatine (Lac/Cr).
Ala was only detected in the 5 SEF piglets. During SEF evolution we observed progressively increasing thalamic Ala/Cr and Lac/Cr. When the final measurements were compared both Lac/Cr and Ala/Cr separately showed inverse linear correlations with [NTP]/[EPP] and [PCr]/[Pi] (all p<0.05) (Figure 1).
Conclusions: Both Ala/Cr and Lac/Cr increased concomitant with the development and proportional to the severity of SEF. These observations are consistent with decreased pyruvate flux through the Krebs cycle and increased flux through lactate-dehydrogenase and AAT during the evolution of SEF leading to concomitant accumulation of Lac and Ala respectively.
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West, D., Thornton, J., Wylezinska, M. et al. 416 Cerebral Alanine Increases During the Evolution of Secondary Energy Failure Following Transient Hypoxia-Ischaemia in Newborn Brain. Pediatr Res 58, 426 (2005). https://doi.org/10.1203/00006450-200508000-00445
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DOI: https://doi.org/10.1203/00006450-200508000-00445