Blood flow restricted resistance exercise and reductions in oxygen tension attenuate mitochondrial H₂O₂ emission rates in human skeletal muscle

Abstract

Key pointsr Blood flow restricted resistance exercise (BFR-RE) is capable of inducing comparable adaptations to traditional resistance exercise (RE), despite a lower total exercise volume.r It has been suggested that an increase in reactive oxygen species (ROS) production may be involved in this response; however, oxygen partial pressure (P O 2 ) is reduced during BFR-RE, and the influence of P O 2 on mitochondrial redox balance remains poorly understood.r In human skeletal muscle tissue, we demonstrate that both maximal and submaximal mitochondrial ROS emission rates are acutely decreased 2 h following BFR-RE, but not RE, occurring along with a reduction in tissue oxygenation during BFR-RE.r We further suggest that P O 2 is involved in this response because an in vitro analysis revealed that reducing P O 2 dramatically decreased mitochondrial ROS emissions and electron leak to ROS.r Altogether, these data indicate that mitochondrial ROS emission rates are attenuated following BFR-RE, and such a response is likely influenced by reductions in P O 2 .Abstract Low-load blood flow restricted resistance exercise (BFR-RE) training has been proposed to induce comparable adaptations to traditional resistance exercise (RE) training, however, the acute signalling events remain unknown. Although a suggested mechanism of BFR-RE is an increase in reactive oxygen species (ROS) production, oxygen partial pressure (P O 2 ) is H. L. Petrick and others J Physiol 597.15 reduced during BFR-RE, and the influence of O 2 tension on mitochondrial redox balance remains ambiguous. We therefore aimed to determine whether skeletal muscle mitochondrial bioenergetics were altered following an acute bout of BFR-RE or RE, and to further examine the role of P O 2 in this response. Accordingly, muscle biopsies were obtained from 10 males at rest and 2 h after performing three sets of single-leg squats (RE or BFR-RE) to failure at 30% one-repetition maximum. We determined that mitochondrial respiratory capacity and ADP sensitivity were not altered in response to RE or BFR-RE. Although maximal (succinate) and submaximal (non-saturating ADP) mitochondrial ROS emission rates were unchanged following RE, BFR-RE attenuated these responses by ß30% compared to pre-exercise, occurring along with a reduction in skeletal muscle tissue oxygenation during BFR-RE (P < 0.01 vs. RE). In a separate cohort of participants, evaluation of mitochondrial bioenergetics in vitro revealed that mild O 2 restriction (50 µM) dramatically attenuated maximal (ß4-fold) and submaximal (ß50-fold) mitochondrial ROS emission rates and the fraction of electron leak to ROS compared to room air (200 µM). Combined, these data demonstrate that mitochondrial ROS emissions are attenuated following BFR-RE, a response which may be mediated by a reduction in skeletal muscle P O 2 .

Quantitative Redox Biology of Exercise

“…The literature quantified in the following refers to both animals and humans (mice, 18 studies [68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85]; rats, 6 studies [86][87][88][89][90][91]; and humans, 3 studies [73,92,93]; one study used both mice and humans [73]. There was no restriction to the type of acute exercise used.…”

“…Most animal studies used electrical stimulation (either on muscle cells or on whole muscle [68-72, 75, 76, 78-85, 87-91] and only 4 animal studies used a more physiological type of exercise (i.e., endurance exercise on a treadmill [73,74,77,86]. The 3 human studies used different exercise protocols (endurance exercise on a bicycle or treadmill and resistance exercise [73,92,93]. Relevant studies that employed non-physiological exercise models, namely in vitro muscle stimulation or in situ muscle stimulation, are also included.…”

“…Considering also the above-mentioned lack of absolute specificity of probes, we present the data in mitochondria as global RONS. Based on these data, it is clear that the effects of acute exercise on RONS levels in mitochondria are trichotomized: three studies reported no changes [68,76,77], four studies reported decreases ranging from − 6 % to − 56 % (median − 25 %) [73,85,92,93], and seven studies reported increases ranging from 13 % to 200 % (median 42 %) [69, 71, 80-82, 84, 86]. The possible reasons of this variable response in mitochondria is hard to explain and beyond the scope of this paper.…”

Unpacking the mitochondrial bioenergetics of blood flow restricted resistance exercise

“…; Petrick et al . ), and others using arbitrarily applied pressures including 20 mmHg below systolic blood pressure (Goldfarb et al . ), or 1.3 times systolic blood pressure (Neto et al .…”

“…In a recent article in The Journal of Physiology , Petrick et al . () explored the mitochondrial bioenergetic responses to BFR‐RT performed to volitional fatigue. Increased mitochondrial reactive oxygen species (ROS) emission can promote signalling for transcription of mitochondrial genes.…”