Pressure passivity of cerebral mitochondrial metabolism is associated with poor outcome following perinatal hypoxic ischemic brain injury

Subhabrata Mitra, Gemma Bale, David Highton, Roxanna Gunny, Cristina Uria-Avellanal, Alan Bainbridge, Magdalena Sokolska, David Price, Angela Huertas-Ceballos, Giles S Kendall, Judith Meek, Ilias Tachtsidis, Nicola J Robertson

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Hypoxic ischemic encephalopathy (HIE) leads to significant morbidity and mortality. Impaired autoregulation after hypoxia-ischaemia has been suggested to contribute further to injury. Thalamic lactate/N-Acetylasperate (Lac/NAA) peak area ratio of > 0.3 on proton (1H) magnetic resonance spectroscopy (MRS) is associated with poor neurodevelopment outcome following HIE. Cytochrome-c-oxidase (CCO) plays a central role in mitochondrial oxidative metabolism and ATP synthesis. Using a novel broadband NIRS system, we investigated the impact of pressure passivity of cerebral metabolism (CCO), oxygenation (haemoglobin difference (HbD)) and cerebral blood volume (total haemoglobin (HbT)) in 23 term infants following HIE during therapeutic hypothermia (HT). Sixty-minute epochs of data from each infant were studied using wavelet analysis at a mean age of 48 h. Wavelet semblance (a measure of phase difference) was calculated to compare reactivity between mean arterial blood pressure (MABP) with oxCCO, HbD and HbT. OxCCO-MABP semblance correlated with thalamic Lac/NAA ( r = 0.48, p = 0.02). OxCCO-MABP semblance also differed between groups of infants with mild to moderate and severe injury measured using brain MRI score ( p = 0.04), thalamic Lac/NAA ( p = 0.04) and neurodevelopmental outcome at one year ( p = 0.04). Pressure passive changes in cerebral metabolism were associated with injury severity indicated by thalamic Lac/NAA, MRI scores and neurodevelopmental assessment at one year of age.

Original languageEnglish
Pages (from-to)118-130
Number of pages13
JournalJournal of Cerebral Blood Flow and Metabolism
Issue number1
Publication statusPublished - Jan 2019

Keywords / Materials (for Non-textual outputs)

  • Adenosine Triphosphate/biosynthesis
  • Aspartic Acid/analogs & derivatives
  • Blood Pressure
  • Brain/metabolism
  • Cerebrovascular Circulation
  • Developmental Disabilities/diagnostic imaging
  • Electron Transport Complex IV/metabolism
  • Female
  • Homeostasis
  • Humans
  • Hypoxia-Ischemia, Brain/complications
  • Infant, Newborn
  • Lactic Acid/metabolism
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Mitochondria/metabolism
  • Thalamus/metabolism


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