The redox signal: A physiological perspective.

A signal in biology is any kind of coded message sent from one place in an organism to another place. Biology is rich in claims that reactive oxygen and nitrogen species transmit signals. Therefore, we define a "redox signal as an increase/decrease in the level of reactive species". First, as in most biology disciplines, to analyze a redox signal you need first to deconstruct it. The essential components that constitute a redox signal and should be characterized are: (i) the reactivity of the specific reactive species, (ii) the magnitude of change, (iii) the temporal pattern of change, and (iv) the antioxidant condition. Second, to be able to translate the physiological fate of a redox signal you need to apply novel and bioplausible methodological strategies. Important considerations that should be taken into account when designing an experiment is to (i) assure that redox and physiological measurements are at the same or similar level of biological organization and (ii) focus on molecules that are at the highest level of the redox hierarchy. Third, to reconstruct the redox signal and make sense of the chaotic nature of redox processes, it is essential to apply mathematical and computational modeling. The aim of the present study was to collectively present, for the first time, those elements that essentially affect the redox signal as well as to emphasize that the deconstructing, decoding and reconstructing of a redox signal should be acknowledged as central to design better studies and to advance our understanding on its physiological effects.

Muscle Oxygenation, Neural, and Cardiovascular Responses to Isometric and Workload-matched Dynamic Resistance Exercise.

Differences in blood flow patterns and energy cost between isometric and dynamic resistance exercise may result to variant cardiovascular, neural, and muscle metabolic responses. We aimed to compare the cardiovascular, baroreceptor sensitivity, and muscle oxygenation responses between workload-matched, large muscle-mass isometric and dynamic resistance exercises. Twenty-four young men performed an isometric and a dynamic double leg-press protocol (4 sets×2 min) with similar tension time index (workload). Beat-by-beat hemodynamics, baroreceptor sensitivity, muscle oxygenation, and blood lactate were assessed. The increase in blood pressure was greater (p<0.05) in the 1st set during dynamic than isometric exercise (by ~4.5 mmHg), not different in the 2nd and 3rd sets, and greater in the 4th set during isometric exercise (by ~5 mmHg). Dynamic resistance exercise evoked a greater increase in heart rate, stroke volume, cardiac output, and contractility index (p<0.05), and a greater decline in peripheral resistance, baroreceptor sensitivity, and cardiac function indices than isometric exercise (p<0.05). Participants exhibited a greater reduction in muscle oxyhemoglobin and a greater increase in muscle deoxyhemoglobin in dynamic versus isometric exercise (p<0.001-0.05), with no differences in total hemoglobin and blood lactate. In conclusion, large muscle-mass, multiple-set isometric exercise elicits a relatively similar blood pressure but blunted cardiovascular and baroreceptor sensitivity responses compared to workload-matched dynamic resistance exercise. Differences in blood pressure responses between protocols appear small (~5 mmHg) and are affected by the number of sets. The muscle oxidative stimulus is greater during dynamic resistance exercise than workload-matched isometric exercise.

Skeletal muscle and cerebral oxygenation levels during and after submaximal concentric and eccentric isokinetic exercise.

The aim was to investigate the potential differences in muscle (vastus lateralis) and cerebral (prefrontal cortex) oxygenation levels as well as in the number of repetitions and total work output between isokinetic eccentric and concentric exercise at a moderate relative intensity until exhaustion. Ten recreationally active young men underwent two isokinetic exercise sessions either concentric or eccentric, one on each randomly selected leg. The protocols were performed at 60°/s and an intensity corresponding to 60% of the maximal voluntary contraction (MVC) of each contraction type. Concentric torque was significantly lower compared to eccentric torque in both peak values and at values corresponding to 60% of MVC [230 ± 18 Nm vs. 276 ± 19 Nm (P = .014) and 137 ± 12 Nm vs. 168 ± 11 Nm, respectively (P = .010)]. The participants performed 40% more contractions during eccentric compared to concentric exercise [122 ± 15 vs. 78 ± 7, respectively]. No differences were found in the levels of oxyhaemoglobin, deoxyhemoglobin, total haemoglobin and tissue saturation index when eccentric and eccentric exercise regimes were compared (all P > .05). Our results demonstrate that eccentric exercise of moderate intensity leads to greater resistance to fatigue and more work output compared to concentric exercise, despite the comparable muscle and cerebral oxygenation levels.

How Exercise Can Influence Oxidative Stress and Glucose Levels after Pancreatic Resection: A Randomised Controlled Trial.

BACKGROUND: One of the most challenging operations is the resection of the pancreas, which is associated with high morbidity. Metabolic control during the perioperative period remains an issue that is sometimes difficult to manage. OBJECTIVES: Exercise has a positive effect on glycaemic control. The objective of this trial was determining whether exercise has any benefit for oxidative stress and glucose levels. METHOD: The study was an open-label, randomised clinical trial. It has been registered in the International Standard Randomised Controlled Trial registry. The patients were selected according to the Consolidated Standard of Reporting Trials criteria. RESULTS: In total, 56 patients were assessed for eligibility. There was no statistical difference between the 2 groups (the exercise and the control one) regarding the disease characteristics, morbidity or influence of exercise on oxidative stress; however, the control of glucose was superior in the exercise group. CONCLUSIONS: Exercise has a positive effect on glycaemic control in patients after pancreatic resection.

Postoperative Administration of Alpha-tocopherol Enhances Osseointegration of Stainless Steel Implants: An In Vivo Rat Model.

BACKGROUND: Alpha-tocopherol, a well-known antioxidative agent, may have a positive effect on bone formation during the remodeling phase of secondary fracture healing. Fracture healing and osseointegration of implants share common biological pathways; hence, alpha-tocopherol may enhance implant osseointegration. QUESTIONS/PURPOSES: This experimental study in rats assessed the ability of alpha-tocopherol to enhance osseointegration of orthopaedic implants as determined by (1) pull-out strength and removal torque and (2) a histomorphological assessment of bone formation. In addition, we asked, (3) is there a correlation between the administration of alpha-tocopherol and a reduction in postoperative oxidative stress (as determined by malondialdehyde, protein carbonyls, reduced and oxidized glutathione and their ratio, catalase activity and total antioxidant capacity) that develops after implantation of an orthopaedic implant? METHODS: This blinded study was performed in study and control groups, each consisting of 15 young adult male Wistar rats. On Day 0, a custom-designed stainless-steel screw was implanted in the proximal metaphysis of both tibias of all rats. On Day 1, animals were randomized to receive either alpha-tocopherol (40 mg/kg once per day intraperitoneally) or saline (controls). Animals were treated according to identical perioperative and postoperative protocols and were euthanized on Day 29. All animals completed the study and all tibias were suitable for evaluation. Implant pullout strength was assessed in the right tibias, and removal torque and histomorphometric evaluations (that is, volume of newly formed bone surrounding the implant in mm, percentage of newly formed bone, percentage of bone marrow surrounding the implant per optical field, thickness of newly formed bone in µm, percentage of mineralized bone in newly formed bone, volume of mature newly formed bone surrounding the implant in mm and percentage of mineralized newly formed bone per tissue area) were performed in the left tibias. The plasma levels of alpha-tocopherol, malondialdehyde, protein carbonyls, glutathione, glutathione disulfide, catalase, and the total antioxidant capacity were evaluated, and the ratio of glutathione to oxidized glutathione was calculated. RESULTS: All parameters were different between the alpha-tocopherol-treated and control rats, favoring those in the alpha-tocopherol group. The pullout strength for the alpha-tocopherol group (mean ± SD) was 124.9 ± 20.7 newtons (N) versus 88.1 ± 12.7 N in the control group (mean difference -36.7 [95% CI -49.6 to -23.9]; p < 0.001). The torque median value was 7 (range 5.4 to 8.3) versus 5.2 (range 3.6 to 6 ) N/cm (p < 0.001). The newly formed bone volume was 29.8 ± 5.7 X 10 versus 25.2 ± 7.8 X 10 mm (mean difference -4.6 [95% CI -8.3 to -0.8]; p = 0.018), the percentage of mineralized bone in newly formed bone was 74.6% ± 8.7% versus 62.1% ± 9.8% (mean difference -12.5 [95% CI -20.2 to -4.8]; p = 0.003), the percentage of mineralized newly formed bone per tissue area was 40.3 ± 8.6% versus 34.8 ± 9% (mean difference -5.5 [95% CI -10.4 to -0.6]; p = 0.028), the glutathione level was 2 ± 0.4 versus 1.3 ± 0.3 µmol/g of hemoglobin (mean difference -0.6 [95% CI -0.9 to -0.4]; p < 0.001), the median glutathione/oxidized glutathione ratio was 438.8 (range 298 to 553) versus 340.1 (range 212 to 454; p = 0.002), the catalase activity was 155.6 ± 44.6 versus 87.3 ± 25.2 U/mg Hb (mean difference -68.3 [95% CI -95.4 to -41.2]; p < 0.001), the malondialdehyde level was 0.07 ± 0.02 versus 0.14 ± 0.03 µmol/g protein (mean difference 0.07 [95% CI 0.05 to 0.09]; p < 0.001), the protein carbonyl level was 0.16 ± 0.04 versus 0.27 ± 0.08 nmol/mg of protein (mean difference -0.1 [95% CI 0.05 to 0.15]; p = 0.002), the alpha-tocopherol level was 3.9 ± 4.1 versus 0.9 ± 0.2 mg/dL (mean difference -3 [95% CI -5.2 to -0.7]; p = 0.011), and the total antioxidant capacity was 15.9 ± 3.2 versus 13.7 ± 1.7 nmol 2,2-diphenyl-1-picrylhydrazyl radical/g of protein (mean difference -2.1 [95% CI -4.1 to -0.18]; p = 0.008). CONCLUSIONS: These results using an in vivo rat model support that postoperatively administered alpha-tocopherol can enhance the osseointegration of an orthopaedic implant, although a cause and effect relationship between the administration of alpha-tocopherol and a reduction in postoperative stress cannot be securely established. CLINICAL RELEVANCE: These findings suggest that postoperative administration of alpha-tocopherol is a promising approach to enhance osseointegration of orthopaedic implants in patients. Further studies with different animal models and/or different implants and those evaluating the alpha-tocopherol dose response are needed before performing clinical trials that will examine whether these promising, preliminary results can be extrapolated to the clinical setting as well.

Myosin heavy chain isoform composition in the deltoid and vastus lateralis muscles of elite handball players.

The purpose of the present study was to compare the myosin heavy chain (MHC) isoform composition of the deltoid and vastus lateralis muscles of the dominant and non-dominant limbs in handball players. Eleven male Greek elite handball players (age 22.6 ± 1.9 yrs, training experience 10.6 ± 2.1 yrs, height 184.1 ± 4.1 cm, and weight 81.0 ± 12.5 kg) participated in the study. Four muscle biopsies were obtained from the dominant and non-dominant deltoid and vastus lateralis muscles during the in-season period. The MHC composition was determined using SDS-PAGE. No significant difference was found between the dominant and non-dominant muscles; Deltoid muscle: MHC I [(95%CI = -1.22, 0.33), P = 0.228], MHC ΙΙa [(95%CI = -0.32, 1.59), P = 0.168] and MHC IIx [(95%CI = -1.49, 1.10), P = 0.749]; Vastus lateralis muscle: MHC I [(95%CI = -0.38, 0.63), P = 0.586], MHC ΙΙa [(95%CI = -0.50, 0.65), P = 0.783] and MHC IIx [(95%CI = -1.08, 0.42), P = 0.355]. The findings of the present study indicate that the greater use of the dominant limbs for throwing actions and body movements in handball do not lead to altered MHC isoform composition compared to the non-dominant limbs.

Inspiratory muscle training effects on oxygen saturation and performance in hypoxemic rowers: Effect of sex.

Exercise-induced arterial hypoxemia (EIAH) has been consistently reported in elite endurance athletes. This study examined the effects of an inspiratory muscle training protocol (IMT) on resting pulmonary function, end-exercise arterial oxygen saturation and performance in hypoxemic rowers. Twenty male and sixteen female well-trained hypoxemic rowers were divided into four groups: IMT-male, control-male, IMT-female and control-female. The IMT groups, additionally to the regular training, performed IMT (30 min/day, 5 times/week, 6 weeks). Before and after training, groups underwent an incremental rowing test, a 2000-m time trial and a 5-min "all-out" race. IMT increased respiratory strength in the IMT-male (135 ± 31 vs. 180 ± 22 cmH2O) and IMT-female (93 ± 19 vs. 142 ± 22 cmH2O) (P < 0.05). The IMT-female group exhibited lower EIAH and improved rowing performance in the 2000-m time trial (487 ± 32 vs. 461 ± 34 sec) and in the 5-min "all-out" test (1,285 ± 28 vs. 1,310 ± 36m) (P < 0.05). IMT protocol improved performance in IMT-male only in the 5-min test (1,651 ± 31 vs. 1,746 ± 37m) (P < 0.05). IMT may be a useful tool for increasing respiratory strength and enhancing performance in hypoxemic rowers, especially for women. Abbreviations: EIAH: Exercise-induced arterial hypoxemia; IMT: inspiratory muscle training protocol; PaO2: partial pressure of arterial oxygen; SaO2: arterial oxyhemoglobin saturation; VO2max: maximal oxygen consumption; [(A-a)DO2]: alveolar-to-arterial oxygen difference; VA/Q: ventilation-perfusion inequality/mismatching; PImax: maximal inspiratory pressure; BMI: body mass index; BSA: body surface area; FVC: vital capacity; FEV1: forced expiratory volume in 1 sec; VCin: vital capacity; MVV12: maximal voluntary ventilation in 12 sec.

Beetroot Increases Muscle Performance and Oxygenation During Sustained Isometric Exercise, but Does Not Alter Muscle Oxidative Efficiency and Microvascular Reactivity at Rest.

OBJECTIVE: To examine the effects of beetroot juice (BRJ) on (i) in vivo skeletal muscle O2 consumption (mVO2) and microvascular reactivity at rest and (ii) muscle performance, muscle oxygenation, and mVO2 during sustained isometric handgrip exercise (IHG). METHODS: Sixteen young males consumed, randomly, a nitrate-rich (8.1 mmol BRJnitrate) or nitrate-depleted (BRJplacebo) BRJ. After 2.5 hours, they performed an occlusion-reperfusion maneuver at rest, a 3-minute sustained IHG, and a sustained IHG to exhaustion with arterial occlusion. Changes in muscle oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb), microvascular red blood cell content (tHb), and mVO2 were measured using near-infrared spectroscopy. Force output was recorded. RESULTS: During occlusion, the O2Hb decline did not differ between BRJnitrate and BRJplacebo (magnitude: -30.3 ± 1.6 vs. -31.1 ± 1.5 ΔµΜ; slope: -0.107 ± 0.007 vs. -0.111 ± 0.007 µΜ second-1). During reperfusion, all microvascular reactivity indices were not altered after BRJnitrate (e.g., O2Hbslope: 1.584 ± 0.093 vs. 1.556 ± 0.072 µΜ second-1). During the second and third minute of IHG, O2Hb and tHb were higher in BRJnitrate versus BRJplacebo (p < 0.05), and force output was higher during the third minute (10.8 ± 0.7 vs. 9.5 ± 1.2 kg; p < 0.05); HHb did not differ between trials. In IHG with arterial occlusion, BRJnitrate prolonged the time to fatigue (94.1 ± 5.8 vs. 80.1 ± 3.3 seconds; p < 0.01), with no effects on O2Hb decline (O2Hbslope: -0.226 ± 0.015 vs. -0.230 ± 0.026 µΜ s-1) and mVO2 (14.1 ± 1.0 vs. 14.3 ± 1.6 µmol l-1 minute-1). CONCLUSION: Acute BRJ ingestion in moderately trained individuals (i) did not alter in vivo skeletal muscle microvascular reactivity (index of microvascular function at rest) and basal oxidative efficiency, (ii) increased muscle oxygenation during IHG (possibly via enhanced O2 delivery), and (iii) provided ergogenic benefits during sustained IHG with no effects on muscle oxidative efficiency. The ergogenic effects of BRJ appeared independent of its tissue perfusion benefits.

Muscle Twitch Torque During Two Different in Volume Isometric Exercise Protocols: Fatigue Effects on Postactivation Potentiation.

Xenofondos, A, Bassa, E, Vrabas, IS, Kotzamanidis, C, and Patikas, D. Muscle twitch torque during two different in volume isometric exercise protocols: fatigue effects on postactivation potentiation. J Strength Cond Res 32(2): 578-586, 2018-The purpose of this study was to quantify the effect of the contraction duration of 2 isometric exercise protocols on the postactivation potentiation of 14 well-trained men (age: 22.6 ± 2.8 years, height: 180.3 ± 5.9 cm, and body mass: 72.3 ± 37.9 kg). The protocols consisted of 4 × 6 maximal plantar flexions, of 3-second (P3) or 6-second (P6) duration, performed in random order, with a 2-minute and 15-second intervals between the sets and repetitions, respectively. The torque during maximal isometric voluntary contraction (MIVC), the peak twitch torque (TT), and the rate of torque development (RTD) after each MIVC were analyzed for the first and the last trial of each set, the average of all trials of each set, and the trials within each set that had the highest peak TT. The MIVC had an overall greater reduction during P6 compared with P3 (P3: -4.6 ± 2.3 vs. P6: -16.0 ± 1.9%). P6 showed higher potentiation in TT during the initial repetitions of the first 2 sets (p < 0.05) in contrast to the P3, which revealed a lower potentiation but for a longer period along the exercise session. However, both protocols had on average the same potential for potentiation (P3: 81.6 ± 6.1 vs. P6: 79.8 ± 6.3%). The twitch RTD presented no systematic difference between the 2 protocols (p > 0.05). These data demonstrate the dependence of the TT potentiation on the conditioning stimulus and verify the cumulative effect of potentiation, suggesting the implementation of longer contractions to achieve maximal but temporal TT potentiation and shorter contractions for less variable but prolonged potentiation.

Impairments in microvascular function and skeletal muscle oxygenation in women with gestational diabetes mellitus: links to cardiovascular disease risk factors.

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is a risk factor for the development of endothelial dysfunction and cardiovascular disease. However, in vivo microvascular endothelial function in GDM has not been investigated. This study aimed to examine, using near-infrared spectroscopy (NIRS), whether: (1) there are differences in microvascular reactivity and skeletal muscle oxygen consumption (m[Formula: see text]) at rest and during exercise between GDM and uncomplicated pregnancies; and (2) there is an association of NIRS indices with macrovascular function and cardiovascular disease risk factors. METHODS: Twenty-nine pregnant women (13 with GDM and 16 women with uncomplicated pregnancy, 28 ± 2 gestational weeks) underwent arterial stiffness (pulse wave velocity [PWV]) and 24 h ambulatory BP (24 h BP) evaluation. NIRS continuously monitored, non-invasively, changes in muscle oxygenated and deoxygenated haemoglobin and tissue O2 saturation index (TSI, %) during arterial occlusion/reperfusion and intermittent handgrip exercise. m[Formula: see text] and vascular reactivity indices were calculated. RESULTS: During occlusion and reperfusion, women with GDM exhibited slower TSI response (occlusion slope: -0.06 ± 0.02 vs -0.10 ± 0.04, in GDM and controls, respectively; reperfusion slope: 0.65 ± 0.26 vs 1.05 ± 0.41, respectively), lower m[Formula: see text] (1.3 ± 1.2 vs 3.8 ± 2.3 µmol l-1 min-1) and blunted hyperaemia (ΔTSI 6.8 ± 2.9 vs 9.5 ± 3.4) compared with controls (p < 0.01). Despite similar handgrip strength in the GDM and control groups (29.1 ± 8.1 vs 26.2 ± 10.4 kg, respectively), during repeated forearm contractions, women with GDM presented a blunted TSI response (6.5 ± 3.9 vs 19.2 ± 10.9; p < 0.01) and a reduced capacity to maintain the predetermined handgrip (23.4 ± 2.9 vs 27.4 ± 3.8%, p < 0.05). NIRS indices correlated with PWV, 24 h BP and blood glucose concentration earlier in pregnancy (r = 0.40-0.60; p < 0.05). CONCLUSIONS/INTERPRETATION: Women with GDM exhibited a characteristic blunted TSI curve, showing alterations in muscle oxygenation and microvascular responsiveness compared with women with uncomplicated pregnancies. These alterations were manifested during exercise and possibly contribute to the reduced exercise tolerance in GDM. NIRS indices correlated with macrovascular indices (arterial stiffness) and 24 h BP.

Anterior cruciate ligament deficiency reduces walking economy in "copers" and "non-copers".

PURPOSE: Patients with ACL injury requiring surgical treatment (non-copers) demonstrate altered neuromuscular control and gait pattern compared with those returning to their pre-injury activities without surgery (copers). Pathological gait pattern may increase the energy cost of walking. We compared the energy cost of flat, uphill, and downhill walking between ACL-deficient and healthy individuals and between "copers" and "non-copers". METHODS: Nineteen young males with unilateral ACL injury were allocated into "copers" and "non-copers" according to their ability to return to pre-injury activity without ACL reconstruction. Lysholm and IKDC scales were recorded, and a control group (n = 10) matched for physical characteristics and activity levels was included. All participants performed 8-min walking tasks at 0, +10, and -10 % gradients. Energy cost was assessed by measurement of oxygen consumption (VO2). HR and ventilation (VE), respiratory exchange ratio (RER), and VE/VO2 were also measured. RESULTS: VO2 and HR were higher in ACL-deficient patients than in controls during walking at 0, +10, and -10 % gradients (p < 0.01-0.05). There were no differences between "copers" and "non-copers" in VO2 and HR for any gradient. No differences were observed in VE, RER, and VE/VO2 among the three groups. CONCLUSIONS: The walking economy of level, uphill, and downhill walking is reduced in ACL-deficient patients. Despite the improved functional and clinical outcome of "copers", their walking economy appears similar to that of "non-copers" but impaired compared with healthy individuals. The higher energy demand and effort during locomotion in "copers" and "non-copers" has clinical implications for designing safer rehabilitation programmes. The increased energy cost in "copers" may be another parameter to consider when deciding on the most appropriate therapeutic intervention (operative and non-operative), particularly for athletes. LEVEL OF EVIDENCE: II.

Anatomic single-bundle anterior cruciate ligament reconstruction improves walking economy: hamstrings tendon versus patellar tendon grafts.

PURPOSE: Anterior cruciate ligament (ACL) injury is associated with a pathologic gait pattern and increased energy cost during locomotion. ACL reconstruction could improve the gait pattern. Hamstrings tendon (HAM) and bone-patellar tendon-bone (BPTB) grafts are usually used for reconstruction. The aim of this study was to compare the efficacy of anatomic ACL reconstruction with HAM and BPTB grafts on improving and normalizing the energy cost and physiologic reserves during flat, uphill, and downhill walking. METHODS: Twenty male subjects with unilateral ACL injuries were randomly assigned to ACL reconstruction with a HAM (n = 10) or BPTB (n = 10) graft. Ten matched controls were also enrolled. All participants performed three 8-min walking tasks at 0, +10, and -10 % gradients before and 9 months after surgery. Energy cost (oxygen consumption, VO2), heart rate (HR), and ventilation (VE) were measured. Lysholm/IKDC scores were recorded. RESULTS: Pre-operatively, VO2, HR, and VE were higher in the HAM and BPTB groups than in controls during walking at 0, +10, and -10 % gradients (p < 0.001-0.01). Post-operatively, both HAM and BPTB groups showed reduced VO2, HR, and VE during the three walking tasks (p < 0.001-0.01). Although the post-operative VO2 in both surgical groups reached 90-95 % of the normative (control) value during walking, it remained elevated against the value observed in controls (p < 0.001-0.01). The HAM and BPTB groups showed no differences in post-surgical VO2 or HR during walking at all three gradients. CONCLUSION: Anatomic ACL reconstruction with either HAM or BPTB graft resulted in similar short-term improvements in energy cost and nearly normalized locomotion economy and cardiorespiratory reserves during flat, uphill, and downhill walking. The improved locomotion economy is an additional benefit of anatomic ACL reconstruction, irrespective of the type of graft used, that the orthopaedic surgeons should consider. LEVEL OF EVIDENCE: II.

Global Metabolic Stress of Isoeffort Continuous and High Intensity Interval Aerobic Exercise: A Comparative 1H NMR Metabonomic Study.

The overall metabolic/energetic stress that occurs during an acute bout of exercise is proposed to be the main driving force for long-term training adaptations. Continuous and high-intensity interval exercise protocols (HIIE) are currently prescribed to acquire the muscular and metabolic benefits of aerobic training. We applied 1H NMR-based metabonomics to compare the overall metabolic perturbation and activation of individual bioenergetic pathways of three popular aerobic exercises matched for effort/strain. Nine men performed continuous, long-interval (3 min), and short-interval (30 s) bouts of exercise under isoeffort conditions. Blood was collected before and after exercise. The multivariate PCA and OPLS-DA models showed a distinct separation of pre- and postexercise samples in three protocols. The two models did not discriminate the postexercise overall metabolic profiles of the three exercise types. Analysis focused on muscle bioenergetic pathways revealed an extensive upregulation of carbohydrate-lipid metabolism and the TCA cycle in all three protocols; there were only a few differences among protocols in the postexercise abundance of molecules when long-interval bouts were performed. In conclusion, continuous and HIIE exercise protocols, when performed with similar effort/strain, induce comparable global metabolic response/stress despite their marked differences in work-bout intensities. This study highlights the importance of NMR metabonomics in comprehensive monitoring of metabolic consequences of exercise training in the blood of athletes and exercising individuals.

Exaggerated haemodynamic and neural responses to involuntary contractions induced by whole-body vibration in normotensive obese versus lean women.

What is the central question of this study? In obesity, the exaggerated blood pressure response to voluntary exercise is linked to hypertension, yet the mechanisms are not fully elucidated. We examined whether involuntary contractions elicit greater haemodynamic responses and altered neural control of blood pressure in normotensive obese versus lean women. What is the main finding and its importance? During involuntary contractions induced by whole-body vibration, there were augmented blood pressure and spontaneous baroreflex responses in obese compared with lean women. This finding is suggestive of an overactive mechanoreflex in the exercise-induced hypertensive response in obesity. Passive contractions did not elicit differential heart rate responses in obese compared with lean women, implying other mechanisms for the blunted heart rate response reported during voluntary exercise in obesity. In obesity, the exaggerated blood pressure (BP) response to exercise is linked to hypertension, yet the mechanisms are not fully elucidated. In this study, we examined whether involuntary mechanical oscillations, induced by whole-body vibration (WBV), elicit greater haemodynamic responses and altered neural control of BP in obese versus lean women. Twenty-two normotensive, premenopausal women (12 lean and 10 obese) randomly underwent a passive WBV (25 Hz) and a control protocol (similar posture without WVB). Beat-by-beat BP, heart rate, stroke volume, systemic vascular resistance, cardiac output, parasympathetic output (evaluated by heart rate variability) and spontaneous baroreceptor sensitivity (sBRS) were assessed. We found that during WBV, obese women exhibited an augmented systolic BP response compared with lean women that was correlated with body fat percentage (r = 0.77; P < 0.05). The exaggerated BP rise was driven mainly by the greater increase in cardiac output index in obese versus lean women, associated with a greater stroke volume index in obese women. Involuntary contractions did not elicit a differential magnitude of responses in heart rate, heart rate variability indices and systemic vascular resistance in obese versus lean women; however, they did result in greater sBRS responses (P < 0.05) in obese women. In conclusion, involuntary contractions elicited an augmented BP and sBRS response in normotensive obese versus lean women. The greater elevations in circulatory haemodynamics in obese women are suggestive of an overactive mechanoreflex in the exercise-induced hypertensive response in obesity.

Low vitamin C values are linked with decreased physical performance and increased oxidative stress: reversal by vitamin C supplementation.

PURPOSE: It has been suggested that part of the failure of antioxidant supplementation to reduce oxidative stress and promote health is that it has been administered in humans with normal levels of antioxidants. METHODS: To test this hypothesis, we screened 100 males for vitamin C baseline values in blood. Subsequently, the 10 individuals with the lowest and the 10 with the highest vitamin C values were assigned in two groups. Using a placebo-controlled crossover design, the 20 selected subjects performed aerobic exercise to exhaustion (oxidant stimulus) before and after vitamin C supplementation for 30 days. RESULTS: The low vitamin C group had lower VO2max values than the high vitamin C group. Vitamin C supplementation in this group marginally increased VO2max. Baseline concentration of F2-isoprostanes and protein carbonyls was higher in the low vitamin C group compared to the high vitamin C group. Vitamin C supplementation decreased the baseline concentration of F2-isoprostanes and protein carbonyls in both groups, yet the decrease was greater in the low vitamin C group. Before vitamin C supplementation, F2-isoprostanes and protein carbonyls were increased to a greater extent after exercise in the high vitamin C group compared to the low vitamin C group. Interestingly, after vitamin C supplementation, this difference was narrowed. CONCLUSION: We show for the first time that low vitamin C concentration is linked with decreased physical performance and increased oxidative stress and that vitamin C supplementation decreases oxidative stress and might increase exercise performance only in those with low initial concentration of vitamin C.

The rat closely mimics oxidative stress and inflammation in humans after exercise but not after exercise combined with vitamin C administration.

PURPOSE: The purpose of the present study was to directly compare oxidative stress and inflammation responses between rats and humans. METHODS: We contrasted rat and human oxidative stress and inflammatory responses to exercise (pro-oxidant stimulus) and/or vitamin C (anti-oxidant stimulus) administration. Vitamin C was administered orally in both species (16 mg kg(-1) of body weight). Twelve redox biomarkers and seven inflammatory biomarkers were determined in plasma and erythrocytes pre- and post-exercise or pre- and post-exercise combined with vitamin C administration. RESULTS: Exercise increased oxidative stress and induced an inflammatory state in rats and humans. There were only 1/19 significant species × exercise interactions (catalase), indicating similar responses to exercise between rats and humans in redox and inflammatory biomarkers. Vitamin C decreased oxidative stress and increased antioxidant capacity only in humans and did not affect the redox state of rats. In contrast, vitamin C induced an anti-inflammatory state only in rats and did not affect the inflammatory state of humans. There were 10/19 significant species × vitamin C interactions, indicating that rats poorly mimic human oxidative stress and inflammatory responses to vitamin C administration. Exercise after acute vitamin C administration altered redox state only in humans and did not affect the redox state of rats. On the contrary, inflammation biomarkers changed similarly after exercise combined with vitamin C in both rats and humans. CONCLUSIONS: The rat adequately mimics human responses to exercise in basic blood redox/inflammatory profile, yet this is not the case after exercise combined with vitamin C administration.

Blood reflects tissue oxidative stress: a systematic review.

We examined whether the levels of oxidative stress biomarkers measured in blood reflect the tissue redox status. Data from studies that measured redox biomarkers in blood, heart, liver, kidney and skeletal muscle were analyzed. In seven out of nine investigated redox biomarkers (malondialdehyde, reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase, vitamin C and E) there was generally good qualitative and quantitative agreement between the blood and tissues. In contrast, oxidized glutathione and the reduced to oxidized glutathione ratio showed poor agreement between the blood and tissues. This study suggests that most redox biomarkers measured in blood adequately reflect tissue redox status.

Circulating angiogenic biomolecules at rest and in response to upper-limb exercise in individuals with spinal cord injury.

OBJECTIVE: Individuals with spinal cord injury (SCI) show structural and functional vascular maladaptations and muscle loss in their lower limbs. Angiogenic biomolecules play important roles in physiological and pathological angiogenesis, and are implicated in the maintenance of muscle mass. This study examined the responses of angiogenic molecules during upper-limb aerobic exercise in patients with SCI and in able-bodied (AB) individuals. METHODS: Eight SCI patients with thoracic lesions (T6-T12, ASIA A) and eight AB individuals performed an arm-cranking exercise for 30 minutes at 60% of their VO2max. Plasma concentrations of vascular endothelial growth factor (VEGF-A165), VEGF receptor 1 (sVEGFr-1), VEGF receptor 2 (sVEGFr-2), metalloproteinase 2 (MMP-2), and endostatin were measured at rest, after exercise, and at 1.5 and 3.0 hours during recovery. RESULTS: The two-way analysis of variance showed non-significant main effects of "group" and significant main effects of "time/exercise" for all angiogenic biomolecules examined (P < 0.01-0.001). The arm-cranking exercise significantly increased plasma concentrations of VEGF, sVEGFr-1, sVEGFr-2, MMP-2, and endostatin in both groups (P < 0.001-0.01). The magnitude of the increase was similar in both patients with SCI and AB individuals, as shown by the non-significant group × time interaction for all angiogenic parameters. CONCLUSIONS: Upper-limb exercise (arm-cranking for 30 minutes at 60% of VO2max) is a sufficient stimulus to trigger a coordinated circulating angiogenic response in patients with SCI. The response of angiogenic molecules to upper-limb aerobic exercise in SCI appears relatively similar to that observed in AB individuals.

Erythrocyte metabolism.

Our aim is to present an updated overview of the erythrocyte metabolism highlighting its richness and complexity. We have manually collected and connected the available biochemical pathways and integrated them into a functional metabolic map. The focus of this map is on the main biochemical pathways consisting of glycolysis, the pentose phosphate pathway, redox metabolism, oxygen metabolism, purine/nucleoside metabolism, and membrane transport. Other recently emerging pathways are also curated, like the methionine salvage pathway, the glyoxalase system, carnitine metabolism, and the lands cycle, as well as remnants of the carboxylic acid metabolism. An additional goal of this review is to present the dynamics of erythrocyte metabolism, providing key numbers used to perform basic quantitative analyses. By synthesizing experimental and computational data, we conclude that glycolysis, pentose phosphate pathway, and redox metabolism are the foundations of erythrocyte metabolism. Additionally, the erythrocyte can sense oxygen levels and oxidative stress adjusting its mechanics, metabolism, and function. In conclusion, fine-tuning of erythrocyte metabolism controls one of the most important biological processes, that is, oxygen loading, transport, and delivery.

Determinants of muscle metaboreflex and involvement of baroreflex in boys and young men.

This study aimed to assess the arterial pressure (AP) determinants during the muscle metaboreflex in boys and men and to investigate the contribution of baroreflex and sympathovagal function to the metaboreflex-induced responses. Fourteen pre-adolescent boys and 13 men performed a protocol involving: baseline, isometric handgrip exercise, circulatory occlusion, and recovery. The same protocol was repeated without occlusion. During baseline, boys had lower beat-to-beat AP, higher heart rate (HR), and lower low/high frequency HR variability. During exercise, a parasympathetic withdrawal was evident in both groups. In adults, HR was the key contributor to the pressure response, with no changes in stroke volume, whereas in boys, the lower HR increase was counterbalanced by an increase in stroke volume, resulting in similar relative increases in AP in both groups. In recovery, boys exhibited a faster rate of HR-decay, rapid vagal reactivation, and greater decrease in TPR than men. An overshoot in baroreceptor sensitivity was observed in men. The isolated metaboreflex resulted in a similar AP elevation in both age groups (by ~15 mmHg), and attenuated spontaneous baroreceptor sensitivity. However, during the metaboreflex, pre-adolescent males exhibited a lower increase in peripheral resistance and a greater bradycardic response than adults, and a fast restoration of vagal activity to non-occlusion levels. During metaboreflex, boys were capable of eliciting a pressure response similar to the one elicited by men; however, the interplay of the mechanisms underlying the rise in AP differed between the two groups with the vagal contribution being greater in the younger participants.