Hypoxia compounds exercise-induced free radical formation in humans; partitioning contributions from the cerebral and femoral circulation

Damian M. Bailey*, Peter Rasmussen, Kevin A. Evans, Aske M. Bohm, Morten Zaar, Henning B. Nielsen, Patrice Brassard, Nikolai B. Nordsborg, Pernille H. Homann, Peter B. Raven, Jane McEneny, Ian S. Young, Joe M McCord, Niels H. Secher

*Corresponding author for this work

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Abstract

This study examined to what extent the human cerebral and femoral circulation contribute to free radical formation during basal and exercise-induced responses to hypoxia. Healthy participants (5♂ 5♀) were randomly assigned single-blinded to normoxic (21% O2) and hypoxic (10% O2) trials with measurements taken at rest and 30 min after cycling at 70% of maximal power output in hypoxia and equivalent relative and absolute intensities in normoxia. Blood was sampled from the brachial artery (a), internal jugular and femoral veins (v) for non-enzymatic antioxidants (HPLC), ascorbate radical (A•-, electron paramagnetic resonance spectroscopy), lipid hydroperoxides (LOOH) and low density lipoprotein (LDL) oxidation (spectrophotometry). Cerebral and femoral venous blood flow was evaluated by transcranial Doppler ultrasound (CBF) and constant infusion thermodilution (FBF). With 3 participants lost to follow up (final n = 4♂ 3♀), hypoxia increased CBF and FBF (P = 0.041 vs. normoxia) with further elevations in FBF during exercise (P = 0.002 vs. rest). Cerebral and femoral ascorbate and α-tocopherol consumption (v < a) was accompanied by A•-/LOOH formation (v > a) and increased LDL oxidation during hypoxia (P < 0.043–0.049 vs. normoxia) implying free radical-mediated lipid peroxidation subsequent to inadequate antioxidant defense. This was pronounced during exercise across the femoral circulation in proportion to the increase in local O2 uptake (r = −0.397 to −0.459, P = 0.037–0.045) but unrelated to any reduction in PO2. These findings highlight considerable regional heterogeneity in the oxidative stress response to hypoxia that may be more attributable to local differences in O2 flux than to O2 tension.

Original languageEnglish
Pages (from-to)104-113
Number of pages10
JournalFree Radical Biology and Medicine
Volume124
DOIs
Publication statusPublished - 20 Aug 2018
EventEurophysiology 2018 - QEII Centre, London, United Kingdom
Duration: 14 Sep 201816 Sep 2018

Keywords

  • Brain
  • Exercise
  • Free radicals
  • Hypoxia
  • Muscle

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