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

TY - JOUR

T1 - Hypoxia compounds exercise-induced free radical formation in humans; partitioning contributions from the cerebral and femoral circulation

AU - Bailey, Damian M

AU - Rasmussen, Peter

AU - Evans, Kevin A

AU - Bohm, Aske M

AU - Zaar, Morten

AU - Nielsen, Henning B

AU - Brassard, Patrice

AU - Nordsborg, Nikolai Baastrup

AU - Homann, Pernille Halberg

AU - Raven, Peter B

AU - McEneny, Jane

AU - Young, Ian S

AU - McCord, Joe M

AU - Secher, Niels H.

N1 - CURIS 2018 NEXS 209

PY - 2018/8/20

Y1 - 2018/8/20

N2 - 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% O 2 ) and hypoxic (10% O 2 ) 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 O 2 uptake (r = −0.397 to −0.459, P = 0.037–0.045) but unrelated to any reduction in PO 2 . These findings highlight considerable regional heterogeneity in the oxidative stress response to hypoxia that may be more attributable to local differences in O 2 flux than to O 2 tension.

AB - 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% O 2 ) and hypoxic (10% O 2 ) 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 O 2 uptake (r = −0.397 to −0.459, P = 0.037–0.045) but unrelated to any reduction in PO 2 . These findings highlight considerable regional heterogeneity in the oxidative stress response to hypoxia that may be more attributable to local differences in O 2 flux than to O 2 tension.

KW - Faculty of Science

KW - Hypoxia

KW - Exercise

KW - Free radicals

KW - Muscle

KW - Brain

U2 - 10.1016/j.freeradbiomed.2018.05.090

DO - 10.1016/j.freeradbiomed.2018.05.090

M3 - Journal article

C2 - 29859345

SN - 0891-5849

VL - 124

SP - 104

EP - 113

JO - Free Radical Biology & Medicine

JF - Free Radical Biology & Medicine

ER -