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

Presented at the Neonatal Society 2016 Summer Meeting.

Mitra S1, Bale G2, Highton D3, Uria-Avellanal C1, Meek J1, Tachtsidis I1, Robertson NJ1

1 Institute for Women’s Health, University College London (UCL), UK
2 Department of Medical Physics and Biomedical Engineering, UCL, UK
3 Neurocritical Care, National Hospital for Neurology & Neurosurgery, UCL, UK

Background: Impaired pressure autoregulation following hypoxic ischaemic encephalopathy (HIE) contributes further to brain injury (1). Thalamic Lac/NAA peak area ratio on 1H MRS>0.3 is associated with poor neurodevelopment outcome following HIE (2). Cytochrome-c-oxidase (CCO) plays a central role in mitochondrial oxidative metabolism and ATP synthesis (3). We hypothesised that the pressure passivity of cerebral metabolism (CCO), oxygenation (HbD) and cerebral blood volume (HbT) would be associated with poor outcome following HIE.

Methods: Ethical approval and written consent obtained. Using broadband NIRS, Δ[oxCCO], Δ[HbD] and Δ[HbT] were measured in 23 term infants following HIE during cooling. Physiological and NIRS data were synchronised. 60 minute periods of dataset from each infant (clinically stable condition) at a mean age of 48hrs were examined with MATLAB based wavelet analysis. Wavelet semblance (measure of phase differences) and coherence (measure of similarity of oscillations) were used to compare arterial blood pressure (ABP) with CCO, HbD and HbT. Examples of impaired and intact CCO/ABP reactivity are presented in Fig 1A & 1B.

Results: CCO/ABP semblance was better correlated with thalamic Lac/NAA (r=0.49, p=0.02) (Fig 1C) compared to HbD/ABP semblance (r=0.27, p=0.21) and HbT/ABP semblance (r=0.23, p=0.28). CCO/ABP semblance was significantly different between two groups of infants with Lac/NAA<0.3 (n=12) and Lac/NAA>0.3 (n=11) (p=0.04) (Fig 1D). HbD/ABP and HbT/ABP semblance were not significantly different between the groups.

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


Fig 1. Examples of CCO/ABP reactivity in A & B. Linear regression between CCO/ABP semblance and Lac/NAA in C. CCO/ABP semblance in two outcome groups in D.

Conclusion: Pressure passive changes in cerebral mitochondrial CCO following HIE were associated with poor outcome. CCO/ABP semblance was better associated with Lac/NAA, an established outcome biomarker following HIE, in comparison to both HbD/ABP and HbT/ABP semblance.

Corresponding author: subhabrata.mitra.13@ucl.ac.uk

References
1. Burton VJ 2015
2. Thayyil S 2010
3. Bainbridge A.

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