Background: Hyperoxia (HYPER) increases O₂ carrying capacity resulting in a higher O₂ delivery to the working muscles during exercise. Several lines of evidence indicate that lactate metabolism, power output, and endurance are improved by HYPER compared to normoxia (NORM). Since HYPER enables a higher exercise power output compared to NORM and considering the O₂ delivery limitation at exercise intensities near to maximum, we hypothesized that hyperoxic-supplemented high-intensity interval training (HIIT) would upregulate muscle mitochondrial oxidative capacity and enhance endurance cycling performance compared to training in normoxia. Methods: 23 trained cyclists, age 35.3 ± 6.4 years, body mass 75.2 ± 9.6 kg, height 179.8 ± 7.9 m, and VO₂max 4.5 ± 0.7 L min^-1 performed 6 weeks polarized and periodized endurance training on a cycle ergometer consisting of supervised HIIT sessions 3 days/week and additional low-intensity training 2 days/week. Participants were randomly assigned to either HYPER (F_IO₂ 0.30; n = 12) or NORM (F_IO₂ 0.21; n = 11) breathing condition during HIIT. Mitochondrial respiration in permeabilized fibers and isolated mitochondria together with maximal and submaximal VO₂, hematological parameters, and self-paced endurance cycling performance were tested pre- and posttraining intervention. Results: Hyperoxic training led to a small, non-significant change in performance compared to normoxic training (HYPER 6.0 ± 3.7%, NORM 2.4 ± 5.0%; p = 0.073, ES = 0.32). This small, beneficial effect on the self-paced endurance cycling performance was not explained by the change in VO₂max (HYPER 1.1 ± 3.8%, NORM 0.0 ± 3.7%; p = 0.55, ES = 0.08), blood volume and hemoglobin mass, mitochondrial oxidative phosphorylation capacity (permeabilized fibers: HYPER 27.3 ± 46.0%, NORM 16.5 ± 49.1%; p = 0.37, ES = 3.24 and in isolated mitochondria: HYPER 26.1 ± 80.1%, NORM 15.9 ± 73.3%; p = 0.66, ES = 0.51), or markers of mitochondrial content which were similar between groups post intervention. Conclusions: This study showed that 6 weeks hyperoxic-supplemented HIIT led to marginal gain in cycle performance in already trained cyclists without change in VO₂max, blood volume, hemoglobin mass, mitochondrial oxidative phosphorylation capacity, or exercise efficiency. The underlying mechanisms for the potentially meaningful performance effects of hyperoxia training remain unexplained and may raise ethical questions for elite sport.

AIM:We examined the Fick components together with mitochondrial O2 affinity (p50mito ) in defining O2 extraction and O2 uptake during exercise with large and small muscle mass during normoxia (NORM) and hyperoxia (HYPER).

METHODS:Seven individuals performed two incremental exercise tests to exhaustion on a bicycle ergometer (BIKE) and two on a one-legged knee extension ergometer (KE) in NORM or HYPER. Leg blood flow and VO2 were determined by thermodilution and the Fick method. Maximal ADP-stimulated mitochondrial respiration (OXPHOS) and p50mito were measured ex vivo in isolated mitochondria. Mitochondrial excess capacity in the leg was determined from OXPHOS in permeabilized fibers and muscle mass measured with magnetic resonance imaging in relation to peak leg O2 delivery.

RESULTS:The ex vivo p50mito increased from 0.06±0.02 to 0.17±0.04 kPa with varying substrate supply and O2 flux rates from 9.84±2.91 to 16.34±4.07 pmol O2 ·s-1 ·μg-1 respectively. O2 extraction decreased from 83% in BIKE to 67% in KE as a function of a higher O2 delivery, and lower mitochondrial excess capacity. There was a significant relationship between O2 extraction and mitochondrial excess capacity and p50mito that was unrelated to blood flow and mean transit time.

CONCLUSION:O2 extraction varies with mitochondrial respiration rate, p50mito and O2 delivery. Mitochondrial excess capacity maintains a low p50mito which enhances O2 diffusion from microvessels to mitochondria during exercise. This article is protected by copyright. All rights reserved.

Exercise has been suggested to ameliorate the detrimental effects of chemotherapy on skeletal muscle. The aim of this study was to compare the effects of different exercise regimens with usual care on skeletal muscle morphology and mitochondrial markers in patients being treated with chemotherapy for breast cancer. Specifically, we compared moderate-intensity aerobic training combined with high-intensity interval training (AT-HIIT) and resistance training combined with high-intensity interval training (RT-HIIT) with usual care (UC). Resting skeletal muscle biopsies were obtained pre- and postintervention from 23 randomly selected women from the OptiTrain breast cancer trial who underwent RT-HIIT, AT-HIIT, or UC for 16 wk. Over the intervention, citrate synthase activity, muscle fiber cross-sectional area, capillaries per fiber, and myosin heavy chain isoform type I were reduced in UC, whereas RT-HIIT and AT-HIIT were able to counteract these declines. AT-HIIT promoted up-regulation of the electron transport chain protein levels vs. UC. RT-HIIT favored satellite cell count vs. UC and AT-HIIT. There was a significant association between change in citrate synthase activity and self-reported fatigue. AT-HIIT and RT-HIIT maintained or improved markers of skeletal muscle function compared with the declines found in the UC group, indicating a sustained trainability in addition to the preservation of skeletal muscle structural and metabolic characteristics during chemotherapy. These findings highlight the importance of supervised exercise programs for patients with breast cancer during chemotherapy.-Mijwel, S., Cardinale, D. A., Norrbom, J., Chapman, M., Ivarsson, N., Wengström, Y., Sundberg, C. J., Rundqvist, H. Exercise training during chemotherapy preserves skeletal muscle fiber area, capillarization, and mitochondrial content in patients with breast cancer.

Recent technological developments have made it possible to use hyperoxia as an enhancement aid during training. Athletes wearing a mask can breathe a higher fraction of oxygen from a stationary or portable apparatus while exercising. A large body of evidence indicates that the oxygen transport capacity, lactate metabolism, power output and work tolerance (endurance) are improved when breathing hyperoxia. The physiological mechanisms underlying these performance improvements, although still not fully elucidated, are based on higher oxygen delivery and reduced central fatigue. Although much is known about the acute effects of hyperoxia, the effect of hyperoxic-supplemented endurance training on performance and the mechanisms beneath training adaptations are not very well understood, especially in well-trained endurance athletes. The few studies on the physiological effects of hyperoxia training have been conducted with conflicting results, discussed in this paper. Potential detrimental effects have not yet been shown experimentally and warrant further investigation.

Sexual dimorphism is apparent in humans, however, to date no studies have investigated mitochondrial function focusing on intrinsic mitochondrial respiration (i.e., mitochondrial respiration for a given amount of mitochondrial protein) and mitochondrial oxygen affinity (p50_mito) in relation to biological sex in human. A skeletal muscle biopsy was donated by nine active women, and ten men matched for maximal oxygen consumption (VO_2max) and by nine endurance trained men. Intrinsic mitochondrial respiration, assessed in isolated mitochondria, was higher in women compared to men when activating complex I (CI_P) and complex I+II (CI+II_P) (p < 0.05), and was similar to trained men (CI_P, p = 0.053; CI+II_P, p = 0.066). Proton leak and p50_mito were higher in women compared to men independent of VO_2max. In conclusion, significant novel differences in mitochondrial oxidative function, intrinsic mitochondrial respiration and p50_mito exist between women and men. These findings may represent an adaptation in the oxygen cascade in women to optimize muscle oxygen uptake to compensate for a lower oxygen delivery during exercise.

The mitochondrion is one of the most fascinating organelles of our cells which has kept and keeps researchers busy in studying its origin, the complex morphology, the numerous functions, the rapid adaptations to a variety of stimuli and its role in health and disease. Exercise challenges cellular homeostasis and skeletal muscle mitochondria greatly adapt to repeated bouts of exercise by increasing mitochondrial respiratory function and content to match energy requirements and to better sustain future perturbations induced by muscle contractions. The oxidative capacity of mitochondria has been shown to exceed the capacity of the cardiorespiratory system to supply oxygen to active muscle at maximal exercise intensity. Despite this, exercise training further increases this overcapacity. Little is known about the role of this excess oxidative capacity of mitochondria in regulating oxygen consumption, the role of oxygen delivery in determining exercise-induced skeletal muscle adaptations, and whether any sex-related differences exist. The assessment of mitochondrial respiratory function in high resolution respirometer is largely used for clinical and scientific purposes. However, the reliability of this method has not been systematically investigated and warrant further investigation.

With this background, specific measures of reliability associated with repeated determination of maximal mitochondrial oxidative phosphorylation in saponin-permeabilized fibres, comparison of the right and left legs, variability with measurements at different time-points and over time, as well as influence of the local anesthetic and wet weight of the fiber bundle on determined maximal mitochondrial oxidative phosphorylation were investigated in paper I. The importance of having the same technicians in preparing the samples, and that the major source of variation in measuring mitochondrial oxidative capacity is the sample preparation per se were shown. Furthermore, other factors such as the possible difference between left and right limbs, two time points of sample collection, fibres bundle weight, time that elapsed after collection of the biopsy, and the use of an anesthetic have only a minor impact on the standard error of the measurement.

In paper II the physiological significance of having a mitochondrial oxidative capacity in excess of the capacity of the central circulation to deliver oxygen to the tissue was shown by integrating measures of ex vivo mitochondrial respiratory function with direct in vivo measure of oxygen consumption when performing two-legged cycling and one-legged knee extension exercise while inspiring atmospheric air and oxygen enriched air in the same participants. Excess capacity of mitochondria allows submaximal mitochondrial activation at maximal oxygen delivery, thereby maintaining a high mitochondrial oxygen affinity and a high oxygen extraction peripherally. Considering the widespread and increasing sedentary behavior in a society plagued by diseases often linked to mitochondrial dysfunction, these results suggest the importance of preserving a high muscle oxidative capacity throughout life, which can be of significance in patients with heart, circulatory, and overall metabolic diseases.

Despite known sex-specific metabolic differences in human skeletal muscle and that animal models have consistently shown females having a superior mitochondrial function compare to males, data in humans are lacking. In paper III the first evidence that women possess higher mitochondrial quality compared to men with equal cardiorespiratory fitness and endurance performance was provided. Mitochondrial oxygen affinity varied with the degree of mitochondrial respiration rate and was lower in women compared to men. These results indicate that the higher mitochondrial quality in women may be an important physiological adaptation that compensates for the lower mitochondrial oxygen affinity allowing a higher oxygen extraction peripherally. Moreover, these results could possibly be linked to the difference in life expectancy, disease occurrence and aging between women and men.

Lastly, in paper IV it was shown that increasing oxygen delivery and exercise intensity by means of breathing hyperoxia during high-intensity exercise did not enhance cardiorespiratory fitness and exercise-induced skeletal muscle adaptations but still resulted in a small beneficial effect on performance in trained cyclists. This small positive effect on performance can be exploited in elite athletes; however, considering the cost/benefit, the unknown health-related problems, and ethical issues of performing hyperoxic-supplemented endurance training, it is arguable if the use of this strategy to maximize endurance performance is worthwhile.

Overall, this thesis provides useful information for future research on various factors influencing the error of the measurement when assessing mitochondrial respiratory function. Moreover, this thesis sheds light on novel factors that regulate oxygen consumption during exercise, highlighting the importance of maintaining a good mitochondrial function. This thesis also provides possible directions for future studies on mitochondrial function, metabolism and exercise-induced adaptations.  

In healthy individuals maximal oxygen uptake is limited by cardiac output when exercising with large musclemass, e.g. 2-legged cycling (BIKE), whereas during one-leg knee extension (KE) exercise there is a closermatch between the amounts of O2 delivered to O2 demand. However hyperoxia has been shown to increaseO2 uptake in both work modalities. This study examined the extent to which hyperoxia affects leg oxygentransport, muscle diffusion capacity, mitochondrial oxygen affinity (p50mito) in vivo and ex vivo, and muscleO2 uptake during exercise engaging a large and small muscle mass in well-trained individuals. In this studywe show that light hyperoxia increases O2 uptake at peak incremental exercise (~10%, p< 0.05) in bothBIKE and KE due to an increased O2 delivery (~ 10%, p< 0.05), which in turn is mainly caused by anincreased arterial O2 content (~5%, p< 0.05), and a non-significant increased leg blood flow (~ 5%). Hencehyperoxia decreases mitochondrial O2 affinity as indicated by the higher calculated in vivo mitochondrialp50. Inspired O2 enhanced maximal work rate in BIKE (~6.5%) and in KE (~4.5%).Our data show that in vivo mitop50 is lower than the ex vivo measure in BIKE, whereas in vivo mitop50 issimilar to ex vivo measure in KE. These indicates that mitochondrial OXPHOS capacity was in excess inBIKE, whereas in KE was almost fully utilized in vivo. This study indicated that both during whole body peakexercise as well as during exercise with smaller muscle mass, V̇O2 may not limit O2 diffusion capacity.

Vältränade idrottare som andas syrgas ökar omedelbart prestationen. Trots det är metoden inte dopningsklassad. En genomgång av aktuell forskning visar att syrgasandning skulle ha en signifikant effekt under tävlingar, men hur det fungerar som träningsmetod är mer osäkert. Vanlig luft kan vara minst lika bra.