Skeletal Muscle Oxygen Research Articles

Contracting Skeletal Muscle Oxygen Pressures in Rats with Heart Failure: Impact of Soluble Guanylyl Cyclase Activator

Introduction Heart failure with reduced ejection fraction (HFrEF) causes impaired convective and diffusive oxygen (O2) transport, in part, by nitric oxide -soluble guanylyl cyclase (sGC)- cyclic guanosine monophosphate pathway dysfunction. sGC activators were developed to selectively target oxidized, heme-free sGC and promote vasodilation, thereby demonstrating potential for improving skeletal muscle oxygenation in HFrEF. We tested the hypotheses that 5 days of administration of sGC activator BAY 60-2770 would increase the O2 delivery (Q̇O2)-to-V̇O2 ratio in the skeletal muscle interstitial space (PO2is, pressure driving O2 into the contracting myocyte) of HFrEF rats at rest and during twitch contractions. Methods HFrEF was induced in adult male Sprague-Dawley (3-4 mo. old) rats via myocardial infarction (MI) and the development of HFrEF was monitored via transthoracic echocardiography. Following 3 weeks of HFrEF progression, rats were treated with 0.3 mg/kg of BAY 60-2770 via oral gavage twice per day (HFrEF + BAY; n =10) for 5 days prior to the contraction protocol. The control heart failure group (HFrEF; n = 9) received vehicle only. Phosphorescence quenching protocols determined the partial pressure of O2 in the spinotrapezius muscle interstitial space at rest and during twitch contractions. Results The degree of HFrEF was not different between groups as evidenced by ejection fraction (44.7 ± 5.1 vs. 46.3 ± 4.8%), left ventricular end-diastolic pressure (16 ± 1 vs. 14 ± 1 mmHg), and MI size (29 ± 2 vs. 28 ± 3%) (all P > 0.05) . Despite no difference either at rest or during the contracting steady-state, across the on transient (14-22 seconds of contractions) there was a ~30% increase in PO2is in HFrEF + BAY vs HFrEF (P ≤ 0.05), demonstrating a greater pressure head driving oxygen to the contracting myocyte. There was also a decrease in arterial blood lactate in HFrEF + BAY vs HFrEF (P < 0.05). Conclusions These data support that during the rest-contraction transient, BAY 60-2770 increases PO2is in rats with moderate HFrEF at the transition from rest to exercise, which may speed V̇O2 kinetics, thereby reducing lactate accumulation. This supports sGC activators as a therapeutic targeting vasomotor dysfunction in chronic heart failure which has the potential to increase exercise capacity and quality of life in this patient population.

Pilot study of contrast-free MRI reveals significantly impaired calf skeletal muscle perfusion in diabetes with incompressible peripheral arteries.

Patients with diabetes mellitus (DM) are more likely to have densely calcified lesions in the below-the-knee tibial arteries. However, the relationship between peripheral arterial calcification and local skeletal muscle perfusion has not been explored. Thirty subjects were prospectively recruited into three groups in this pilot study: (1) Non-DM: 10 people without DM; (2) DM, ABI < 1.3: 10 people with DM and normal ankle-brachial index (ABI) (0.9-1.3); and (3) DM, ABI ⩾ 1.3: 10 people with DM and ABI ⩾ 1.3. All subjects underwent calf perfusion measurements at rest and during an isometric plantarflexion contraction exercise within the magnetic resonance imaging (MRI) system. The noncontrast MRI techniques were applied to quantitatively assess skeletal muscle blood flow (SMBF) and oxygen extraction fraction (SMOEF) in medial gastrocnemius and soleus muscles. Both SMBF and SMOEF reserves were calculated as the ratio of the exercise value to the resting value. Exercise SMBF and SMOEF values in the medial gastrocnemius muscle were lower in the two DM groups than in the non-DM group (p < 0.05). The SMBF reserve in medial gastrocnemius was significantly lower in the DM, ABI ⩾ 1.3 group compared to the DM, ABI < 1.3 group (p < 0.05). This study demonstrates that people with DM and calcified arteries had lower perfusion in gastrocnemius muscle compared to those without DM and those with DM and a normal ABI.

Single-leg exercise training augments in vivo skeletal muscle oxidative flux and vascular content and function in adults with type 2 diabetes.

People with type 2 diabetes (T2D) have impaired skeletal muscle oxidative flux due to limited oxygen delivery. In the current study, this impairment in oxidative flux in people with T2D was abrogated with a single-leg exercise training protocol. Additionally, single-leg exercise training increased skeletal muscle CD31 content, calf blood flow and state 4 mitochondrial respiration in all participants. Cardiorespiratory fitness is impaired in type 2 diabetes (T2D), conferring significant cardiovascular risk in this population; interventions are needed. Previously, we reported that a T2D-associated decrement in skeletal muscle oxidative flux is ameliorated with acute use of supplemental oxygen, suggesting that skeletal muscle oxygenation is rate-limiting to in vivo mitochondrial oxidative flux during exercise in T2D. We hypothesized that single-leg exercise training (SLET) would improve the T2D-specific impairment in in vivo mitochondrial oxidative flux during exercise. Adults with (n=19) and without T2D (n=22) with similar body mass indexes and levels of physical activity participated in two weeks of SLET. Following SLET, in vivo oxidative flux measured by 31 P-MRS increased in participants with T2D, but not people without T2D, measured by the increase in initial phosphocreatine synthesis (P=0.0455 for the group × exercise interaction) and maximum rate of oxidative ATP synthesis (P=0.0286 for the interaction). Additionally, oxidative phosphorylation increased in all participants with SLET (P=0.0209). After SLET, there was no effect of supplemental oxygen on any of the in vivo oxidative flux measurements in either group (P>0.02), consistent with resolution of the T2D-associated oxygen limitation previously observed at baseline in subjects with T2D. State 4 mitochondrial respiration also improved in muscle fibres ex vivo. Skeletal muscle vasculature content and calf blood flow increased in all participants with SLET (P<0.0040); oxygen extraction in the calf increased only in T2D (P=0.0461). SLET resolves the T2D-associated impairment of skeletal muscle in vivo mitochondrial oxidative flux potentially through improved effective blood flow/oxygen delivery.

Rates of oxidative ATP synthesis are not augmented beyond the pH threshold in human vastus lateralis muscles during a stepwise contraction protocol.

The oxygen cost of high-intensity exercise at power outputs above an individual's lactate threshold (LT) is greater than would be predicted by the linear oxygen consumption-power relationship observed below the LT. However, whether these augmentations are caused by an increased ATP cost of force generation (ATPCOST ) or an increased oxygen cost of ATP synthesis is unclear. We used 31 P-MRS to measure changes in cytosolic [ADP] (intramyocellular marker of oxidative metabolism), oxidative ATP synthesis (ATPOX ) and ATPCOST during a 6-stage, stepwise knee extension protocol. ATPCOST was unchanged across stages. The relationship between [ADP] and muscle power output was augmented at workloads above the pH threshold (pHT ; proxy for LT), whereas increases in ATPOX were attenuated. These results suggest the greater oxygen cost of contractions at workloads beyond the pHT is not caused by mechanisms that increase ATPCOST , but rather mechanisms that alter intrinsic mitochondrial function or capacity. Increases in skeletal muscle metabolism and oxygen consumption are linearly related to muscle power output for workloads below the lactate threshold (LT), but are augmented (i.e. greater rate of increase relative to workload) thereafter. Presently, it is unclear whether these metabolic augmentations are caused by increases in the ATP cost of force generation (ATPCOST ) or changes in the efficiency of mitochondrial oxygen consumption and oxidative ATP synthesis (ATPOX ). To partition these two hypotheses in vivo, we used 31 P-MRS to calculate slopes relating step-changes in muscle work to concurrent changes in cytosolic phosphates and ATPOX before and after the pH threshold (pHT ; used here as a proxy for LT) within the vastus lateralis muscle of eight young adults during a stepwise knee extension test. Changes in muscle phosphates and ATPOX were linearly related to workload below the pHT . However, slopes above the pHT were greater for muscle phosphates (P<0.05) and lower for ATPOX (P<0.05) than were the slopes observed below the pHT . The maximal capacity for ATPOX ( ) and ADP-specific ATPOX also declined beyond the pHT (P<0.05), whereas ATPCOST was unchanged (P=0.10). These results oppose the hypothesis that high-intensity contractions increase ATPCOST and suggest that greater oxidative metabolism at workloads beyond the pHT is caused by mechanisms that affect intrinsic mitochondrial function or capacity, such as alterations in substrate selection or electron entry into the electron transport chain, temperature-mediated changes in mitochondrial permeability to protons, or stimulation of mitochondrial uncoupling by reactive oxygen species generation.

Reduced exercise capacity in patients with systemic sclerosis is associated with lower peak tissue oxygen extraction: a cardiovascular magnetic resonance-augmented cardiopulmonary exercise study

BackgroundExercise intolerance in systemic sclerosis (SSc) is typically attributed to cardiopulmonary limitations. However, problems with skeletal muscle oxygen extraction have not been fully investigated. This study used cardiovascular magnetic resonance (CMR)-augmented cardiopulmonary exercise testing (CMR-CPET) to simultaneously measure oxygen consumption and cardiac output. This allowed calculation of arteriovenous oxygen content gradient, a recognized marker of oxygen extraction. We performed CMR-CPET in 4 groups: systemic sclerosis (SSc); systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH); non-connective tissue disease pulmonary hypertension (NC-PAH); and healthy controls.MethodsWe performed CMR-CPET in 60 subjects (15 in each group) using a supine ergometer following a ramped exercise protocol until exhaustion. Values for oxygen consumption, cardiac output and oxygen content gradient, as well as ventricular volumes, were obtained at rest and peak-exercise for all subjects. In addition, T1 and T2 maps were acquired at rest, and the most recent clinical measures (hemoglobin, lung function, 6-min walk, cardiac and catheterization) were collected.ResultsAll patient groups had reduced peak oxygen consumption compared to healthy controls (p < 0.022). The SSc and SSc-PAH groups had reduced peak oxygen content gradient compared to healthy controls (p < 0.03). Conversely, the SSc-PAH and NC-PH patients had reduced peak cardiac output compared to healthy controls and SSc patients (p < 0.006). Higher hemoglobin was associated with higher peak oxygen content gradient (p = 0.025) and higher myocardial T1 was associated with lower peak stroke volume (p = 0.011).ConclusionsReduced peak oxygen consumption in SSc patients is predominantly driven by reduced oxygen content gradient and in SSc-PAH patients this was amplified by reduced peak cardiac output.Trial registration The study is registered with ClinicalTrials.gov Protocol Registration and Results System (ClinicalTrials.gov ID: 100358).

Aerobic Metabolic Adaptations in Endurance Eccentric Exercise and Training: From Whole Body to Mitochondria.

A characteristic feature of eccentric as compared with concentric exercise is the ability to generate greater mechanical loads for lower cardiopulmonary demands. Current evidence concurs to show that eccentric training translates into considerable gains in muscle mass and strength. Less is known, however, regarding its impact on oxygen transport and on factors to be considered for optimizing its prescription and monitoring. This article reviews the existing evidence for endurance eccentric exercise effects on the components of the oxygen transport system from systemic to mitochondria in both humans and animals. In the studies reviewed, specially designed cycle-ergometers or downhill treadmill running were used to generate eccentric contractions. Observations to date indicate that overall, the aerobic demand associated with the eccentric training load was too low to significantly increase peak maximal oxygen consumption. By extension, it can be inferred that the very high eccentric power output that would have been required to solicit a metabolic demand sufficient to enhance peak aerobic power could not be tolerated or sustained by participants. The impact of endurance eccentric training on peripheral flow distribution remains largely undocumented. Given the high damage susceptibility of eccentric exercise, the extent to which skeletal muscle oxygen utilization adaptations would be seen depends on the balance of adverse and positive signals on mitochondrial integrity. The article examines the protection provided by repeated bouts of acute eccentric exercise and reports on the impact of eccentric cycling and downhill running training programs on markers of mitochondrial function and of mitochondrial biogenesis using mostly from animal studies. The summary of findings does not reveal an impact of training on skeletal muscle mitochondrial respiration nor on selected mitochondrial messenger RNA transcripts. The implications of observations to date are discussed within future perspectives for advancing research on endurance eccentric exercise physiological impacts and using a combined eccentric and concentric exercise approach to optimize functional capacity.

Young healthy adults with a family history of hypertension have increased microvascular reactivity but decreased macrovascular function.

To determine whether, like hypertensives, normotensive adults with a family history of hypertension (+FHH) display lower microvascular reactivity and conduit artery function than normotensive adults without a family history of hypertension (-FHH). A forearm vascular occlusion test was performed on healthy normotensive adults while resting in the supine position. A near-infrared spectroscopy sensor placed on the forearm measured skeletal muscle oxygen saturation kinetics to determine microvascular reactivity. Simultaneously, an ultrasound probe placed on the brachial artery above the occlusion cuff was used to assess flow-mediated dilation; a test of macrovascular function. Twenty-two participants were included in this investigation (-FHH n=13, +FHH n=9). Following cuff release, the resaturation slope (1st 10s median±SD, -FHH 2.76±2.10, +FHH 5.59±2.47%/s; p=.036) was greater in +FHH when accounting for the magnitude and rate of the decrease in skeletal muscle oxygen saturation during occlusion. Conversely, flow-mediated dilation (median±SD, -FHH 5.96±5.22, +FHH 4.10±3.17%∆; p=.031) was lower in +FHH when accounting for baseline artery diameter and shear rate. Young +FHH adults have altered microvascular and macrovascular reactivity compared with young -FHH adults.

Effects of Exercise Training on Cardiac and Skeletal Muscle Functions in Patients with Chronic Heart Failure.

The primary symptom in patients with chronic heart failure (CHF) is exercise intolerance. Previous studies have reported that reduced exercise tolerance in CHF can be explained not only by cardiac output (a central factor) but also by reduced skeletal muscle aerobic capacity (a peripheral factor). Although exercise training in CHF improves exercise tolerance, few studies have evaluated the effects of exercise training on each specific central and peripheral factor in CHF. The aim of this study was to investigate the central and peripheral aerobic functions in CHF and the effects of exercise training in CHF on cardiac output and skeletal muscle deoxygenation during exercise. We assessed peak oxygen uptake (VO2) during cardiopulmonary exercise testing, peak cardiac output (CO) using noninvasive hemodynamic monitoring, and muscle oxygen saturation (SmO2) using near-infrared spectroscopy (NIRS). Patients with CHF were trained for 12weeks and performed ramp cycling exercise until exhaustion before and after the exercise training. Peak VO2, peak CO, and SmO2 changes from rest to peak exercise (ΔSmO2) were significantly lower in CHF than those in healthy subjects. As a result of exercise training, peak oxygen uptake in patients with CHF was improved and positively associated with change in ΔSmO2. In contrast, there was no change in peak cardiac output. The results of this study indicate that both cardiac and skeletal muscle functions in patients with CHF were lower than those in healthy subjects. Further, the results suggest that the improvement of exercise capacity in patients with CHF by exercise training was related to the improved utilization of oxygen (a peripheral factor) in skeletal muscle.

Effects of acute cold stress on energy metabolism, skeletal muscle oxygenation, and exercise performance

Purpose This study aimed to investigate the effects of acute cold stress (10℃, 0℃) compared with ordinary temperature (20℃) on exercise performance and physiological response at rest and during exercise. Methods A total of 10 healthy men (21.55 ± 2.16) were selected. In each environmental condition (20℃, 10℃, 0℃), the three testing order was randomly selected at crossover, and there was a week interval between the graded exercise test (GXT). On the testing day, they remained resting for 30 min in each environmental condition. Dependent variables (body temperature, energy metabolism parameters, skeletal muscle oxygenation profiles, and exercise performance parameters) were measured at rest and during GXT. Results In body temperature, at each environmental condition, there was a significant decrease (p&lt;.05) at 10℃ and 0℃ compared with 20℃ after exercise, and in the difference depending on the environment at rest. After exercise, the body temperature significantly decreased (p&lt;.05) in proportion to the decrease in temperature. There was no difference in heart rate and blood lactate level in energy metabolism, and the respiratory exchange ratio was significantly higher (p&lt;.05) at 0℃ than 20℃. Minute ventilation (VE), oxygen uptake (VO2), and carbon dioxide excretion (VCO2) were significantly lower (p&lt;.05) at 0℃ than 20℃ and 10℃ at various exercise load. All skeletal muscle oxygenation profiles did not show significant changes at rest and during exercise. In exercise performance, maximal oxygen uptake was significantly lower (p&lt;.05) at 0℃ than 20℃, and exercise time to exhaustion was also significantly lower (p&lt;.05) at 0℃ than 20℃ and 10℃. Conclusion Acute cold stress induces deterioration of exercise performance via a decreased body temperature and an increase in VE, VO2, and VCO2 during the same exercise load. In addition it was confirmed that this phenomenon was more prominent at 0°C than at 10°C when compared to 20°C.

Oxygen transport and utilisation during exercise in cystic fibrosis: contributors to exercise intolerance.

What is the topic of this review? This review highlights the central and peripheral mechanisms that alter oxygen transport and utilisation and thereby contribute to exercise limitation in people with cystic fibrosis, considering also viable therapeutic targets for intervention. What advances does it highlight? Although traditionally considered a respiratory condition, pathological intramuscular and cardiovascular changes in people with cystic fibrosis appear to be key determinants of exercise intolerance up until the later stages of respiratory disease. Even young, habitually active patients with normal lung function experience multisystemic abnormalities, which play a role in exercise intolerance. Cystic fibrosis (CF) is a complex condition, commonly associated with exercise limitation. The mechanisms responsible for this in CF are of interest, given that lower aerobic fitness is associated with an increased risk of being hospitalised with pulmonary exacerbation, a poorer quality of life and a poorer prognosis. Pathophysiological changes in lung function are considered central to CF, and may contribute to exercise limitation. However, it is now clear that the pathogenesis of exercise limitation in this population is multifactorial, with alterations in cardiovascular, muscle and pulmonary function contributing. Whilst some of these changes are attributable to respiratory disease per se, the CF transmembrane conductance regulator protein is also found in skeletal muscle and the vascular endothelium and can directly alter central and localised oxygen delivery, as well as the ability to effectively extract and utilise oxygen at the myocyte level. Since intense exercise poses considerable challenges to arterial oxygen content and/or blood flow and its supply to the working skeletal muscle, evaluating the exercise physiology of people with CF has helped us understand the mechanisms underlying exercise intolerance. Through several investigations over recent years, we have collectively demonstrated that people with CF exhibit reduced skeletal muscle oxygen extraction and utilisation during exercise, with a lesser contribution from haemodynamic or chronotropic mechanisms. Taken together, our findings highlight the importance of targeting mechanisms of skeletal muscle oxygen utilisation in CF to improve exercise tolerance and we offer potential therapeutic interventional strategies.

Hyperbaric Oxygen Treatment Following Mid-Cervical Spinal Cord Injury Preserves Diaphragm Muscle Function.

Oxidative damage to the diaphragm as a result of cervical spinal cord injury (SCI) promotes muscle atrophy and weakness. Respiratory insufficiency is the leading cause of morbidity and mortality in cervical spinal cord injury (SCI) patients, emphasizing the need for strategies to maintain diaphragm function. Hyperbaric oxygen (HBO) increases the amount of oxygen dissolved into the blood, elevating the delivery of oxygen to skeletal muscle and reactive oxygen species (ROS) generation. It is proposed that enhanced ROS production due to HBO treatment stimulates adaptations to diaphragm oxidative capacity, resulting in overall reductions in oxidative stress and inflammation. Therefore, we tested the hypothesis that exposure to HBO therapy acutely following SCI would reduce oxidative damage to the diaphragm muscle, preserving muscle fiber size and contractility. Our results demonstrated that lateral contusion injury at C3/4 results in a significant reduction in diaphragm muscle-specific force production and fiber cross-sectional area, which was associated with augmented mitochondrial hydrogen peroxide emission and a reduced mitochondrial respiratory control ratio. In contrast, rats that underwent SCI followed by HBO exposure consisting of 1 h of 100% oxygen at 3 atmospheres absolute (ATA) delivered for 10 consecutive days demonstrated an improvement in diaphragm-specific force production, and an attenuation of fiber atrophy, mitochondrial dysfunction and ROS production. These beneficial adaptations in the diaphragm were related to HBO-induced increases in antioxidant capacity and a reduction in atrogene expression. These findings suggest that HBO therapy may be an effective adjunctive therapy to promote respiratory health following cervical SCI.

Concurrent adaptations in maximal aerobic capacity, heat tolerance, microvascular blood flow and oxygen extraction following heat acclimation and ischemic preconditioning.

We investigated the effects of: 1) Ischemic pre-conditioning (IPC) plus a concurrent five-day heat acclimation+IPC (IPC+HA), 2) five-day HA with sham IPC (HA), or 3) control (CON) on thermoneutral measurements of endurance performance, resting measures of skeletal muscle oxygenation and blood flow. Twenty-nine participants were randomly allocated to three groups, which included: 1) five-days of repeated leg occlusion (4 x 5-min) IPC at limb occlusive pressure, plus fixed-intensity (55% V˙ O2max) cycling HA at ~36°C/40% humidity; 2) HA plus sham IPC (20mmHg) or 3) or CON (thermoneutral 55% V˙ O2max plus sham IPC). In IPC+HA and HA, there were increases in maximal oxygen consumption (O2max) (7.8% and 5.4%, respectively; P<0.05), ventilatory threshold (VT) (5.6% and 2.4%, respectively, P<0.05), delta efficiency (DE) (2.0% and 1.4%, respectively; P<0.05) and maximum oxygen pulse (O2pulse-Max) (7.0% and 6.9%, respectively; P<0.05) during an exhaustive incremental test. There were no changes for CON (P>0.05). Changes (P<0.05) in resting core temperature (TC), muscle oxygen consumption (m V˙ O2), and limb blood flow (LBF) were also found pre-to-post intervention among the HA and IPC+HA groups, but not in CON (P>0.05). Five-days of either HA or IPC+HA can enhance markers of endurance performance in cooler environments, alongside improved muscle oxygen extraction, blood flow, exercising muscle efficiency and O2 pulse at higher intensities, thus suggesting the occurrence of peripheral adaptation. Both HA and IPC+HA enhance the adaptation of endurance capacity, which might partly relate to peripheral changes.

Dietary Nitrate Supplementation and Exercise-Related Performance.

Over the last decade, there has been a growing interest in the utility of nitrate (NO3-) supplementation to improve exercise-related performance. After consumption, dietary NO3- can be reduced to nitric oxide, a free radical gas involved in numerous physiological actions including blood vessel vasodilation, mitochondrial respiration, and skeletal muscle contractile function. Emerging evidence indicates that dietary NO3- supplementation has a small but nevertheless significant beneficial effect on endurance performance through the combined effects of enhanced tissue oxygenation and metabolic efficiency in active skeletal muscle. There is further evidence to suggest that dietary NO3- exerts a direct influence on contractile mechanisms within the skeletal muscle through alterations in calcium availability and sensitivity. Response heterogeneity and sizeable variability in the nitrate content of beetroot juice products influence the effectiveness of dietary NO3- for exercise performance, and so dosing and product quality, as well as training history, sex, and individual-specific characteristics, should be considered.

Rolling massage acutely improves skeletal muscle oxygenation and parameters associated with microvascular reactivity: The first evidence-based study

Although it has been claimed that rolling massage (RM), may lead to improvements in skeletal muscle oxygenation, metabolism, blood flow, and vascular function, scientific evidence has not yet been provided. Thus, the current study investigated the effects of 30 s and 2 min of RM on forearm muscle oxygenation, parameters associated with oxidative metabolism, and microvascular reactivity as well as brachial artery endothelial function. Forearm skeletal muscle parameters were assessed in 12 healthy young men (26 ± 6 yrs) using near-infrared spectroscopy (NIRS) combined with a 5-min vascular occlusion test. Additionally, brachial artery endothelial function was simultaneously assessed by measuring the relative change in brachial artery diameter normalized to the hyperemic blood flow (Normalized %FMD). These measurements were performed before and after the RM interventions performed on the anterior forearm muscles. Forearm muscle oxygenation increased after 30 s of RM (62 ± 7 to 71 ± 11%; p = 0.02) while there was no change from baseline to post-intervention after 2 min of RM. No change was observed for oxidative metabolism, however, the significant main effect (p = 0.02) for NIRS-derived reperfusion slope (%·s−1) indicated that microvascular function improved after both 30 s (2.30 ± 0.5 to 2.61 ± 0.70%·s−1) and 2 min of RM (2.33 ± 0.4 to 2.60 ± 0.85%·s−1). The lack of significant effects of RM on Normalized %FMD suggest that the RM did not acutely improve brachial artery endothelial function. These findings provide, for the first time, evidence that RM improves skeletal muscle oxygenation and parameters associated with microvascular reactivity. Additionally, RM increased brachial artery blood flow, but not upstream brachial artery endothelial function.

Combined anthocyanins and bromelain supplement improves endothelial function and skeletal muscle oxygenation status in adults: a double-blind placebo-controlled randomised crossover clinical trial.

Anthocyanins and bromelain have gained significant attention due to their antioxidative and anti-inflammatory properties. Both have been shown to improve endothelial function, blood pressure (BP) and oxygen utility capacity in humans; however, the combination of these two and the impacts on endothelial function, BP, total antioxidant capacity (TAC) and oxygen utility capacity have not been previously investigated. The purpose of this study was to investigate the impacts of a combined anthocyanins and bromelain supplement (BE) on endothelial function, BP, TAC, oxygen utility capacity and fatigability in healthy adults. Healthy adults (n 18, age 24 (sd 4) years) received BE or placebo in a randomised crossover design. Brachial artery flow-mediated dilation (FMD), BP, TAC, resting heart rate, oxygen utility capacity and fatigability were measured pre- and post-BE and placebo intake. The BE group showed significantly increased FMD, reduced systolic BP and improved oxygen utility capacity compared with the placebo group (P < 0·05). Tissue saturation and oxygenated Hb significantly increased following BE intake, while deoxygenated Hb significantly decreased (P < 0·05) during exercise. Additionally, TAC was significantly increased following BE intake (P < 0·05). There were no significant differences for resting heart rate, diastolic BP or fatigability index. These results suggest that BE intake is an effective nutritional therapy for improving endothelial function, BP, TAC and oxygen utility capacity, which may be beneficial to support vascular health in humans.

The Effect Of Elevation Training Mask On Skeletal Muscle Oxygenation During Walking

Elevation training masks are commonly used to enhance training and performance. While these masks do not generate a hypoxic environment, they are used to train the respiratory system, a common limiting factor in performance in both trained and sedentary individuals. There is limited evidence as to how these masks affect respiration or skeletal muscle oxygenation. PURPOSE: The purpose of this study was to determine how resisted inspiration affects respiration and muscle oxygenation during walking. METHODS: 8 subjects between 18-35 years of age were recruited to walk at 1.6 m/s for 10 minutes with (RI) and without (CON) resisted inspiration. Masks were connected to the metabolic cart and a Moxy monitor was placed on the lateral head of the gastrocnemius to measure muscle oxygenation (SmO) throughout the duration of walking trials. The last 5 minutes of each condition were analyzed and presented as mean ± SD. Student t-test was used to determine significance at p<0.05. RESULTS: RI had no effect on VO2 (CON: 14.17±0.96 RI: 14.23±2.94, p=0.95) or VCO2 (CON: 13.02±0.89 RI: 13.18±2.61, p=0.89). RI caused an average increase of 4.9% in subjects heart rate and induced a significant decrease in respiration rate (CON: 25.93±1.59 RI: 18.63±3.84, p=0.0006). This coincided with no change in total hemoglobin (ThB) in the skeletal muscle (CON: 12.58±0.61 RI: 12.57±0.60, p=0.98) and an increase in 7 out of 8 subject’s SmO with restricted breathing (CON: 41.94±20.15 RI: 48.52±23.08). Despite increased SmO, subjects reported a higher RPE in the RI condition. CONCLUSIONS: During walking, elevation training masks increase skeletal muscle oxygenation. This could be in part due to a longer inspiration allowing for improved blood oxygen saturated. An increased heart rate across most subjects despite no change in ThB could suggest a shift in the hemoglobin dissociation curve allowing more oxygen dissociation in the muscles. Future studies should examine the effect of elevation training masks on muscle oxygenation during higher intensity exercises.

Skeletal Muscle Endurance And Oxygen Uptake Kinetics During Cycling In Patients With High Affinity Hemoglobin

Skeletal muscle oxygen (O2) consumption is linked to the metabolic demand of the exercising skeletal muscle. In hypoxic conditions (e.g. high altitude) O2 consumption may be the limiting factor of exercise tolerance. Patients with increased O2 content, secondary to an increased oxygen affinity (HAH), provide an experiment of nature to investigate the effects of increased flux through the O2 transport pathway on exercise tolerance. PURPOSE: To determine the effect of HAH on O2 uptake kinetics and exercise tolerance during high-intensity exercise under normoxia (NORM) and hypoxia (HYP) conditions. METHODS: Five healthy controls (CTL; 4 men, 41±8 years, P50=27±1 mmHg; Hemoglobin concentration ([Hb])= 14.2±1.3 g· dL-1; hematocrit (Hct)= 43±4%) and five patients with high-affinity hemoglobin (HAH; 3 men, 37±12 years, P50=15±2 mmHg; [Hb]: 19.8±2.3 g·dL-1, Hct= 59±7%) cycled during unloaded pedaling then at a power output that elicited 85% V̇O2max until volitional exhaustion during two different environmental conditions: 1) NORM, (FiO2=0.21), and 2) HYP, (FiO2=0.15). O2 uptake kinetics were modeled as a double-exponential rise to maximum from continuous measurements of inspired/expired gases. Two-way ANOVA with group (HAH, CTL) and inspirate (NORM, HYP) as between-subjects factors were used to compare dependent variables. RESULTS: HAH patients had marked polycythemia (higher [Hb] and Hct, P<0.05 for both). There was no effect of inspirate on any of the parameters of O2 kinetics, all P>0.175). There was no main effect of group or inspirate on V̇O2 during unloaded pedaling (A0, P>0.24), V̇O2 of the primary component (A1, P>0.13), or the V̇O2 slow component (P>0.10). HAH exhibited a trend towards slower O2 kinetics (HAH=64.3±17.7s vs. CTL=49.2±17.0s, P=0.08) and significantly lower primary component amplitude (HAH=1.14±0.66 L·min-1 vs. CTL=1.92±0.67 L·min-1, P=0.02). There was a trend towards reduced time-to-exhaustion in HYP (P=0.09), but no main effect of group (P=0.21). CONCLUSION: Patients with HAH had slower and blunted V̇O2 kinetics, which may be due to 1) blunted O2 off-loading to the contracting skeletal muscle or 2) adaptations of skeletal muscle (e.g. myosin heavy chain expression) to HAH.

Age- And Sex-related Differences In Skeletal Muscle Oxygen Consumption Rate And Microvascular Reactivity

PURPOSE: To examine the influence of age and sex on non-invasive measurements of oxygen consumption rate and microvascular reactivity. METHODS: Seven young females (YF; mean ± SD, age = 20.9±2 y), 6 older females (OF; 57.5±10 y), 14 younger males (YM; 22.2±2 y), and 8 older males (OM; 59.5±5 y) visited the laboratory on one occasion during which skeletal muscle oxygen utilization and microvascular function were assessed following a 10-h fast using the near-infrared spectroscopy with vascular occlusion test (NIRS-VOT). During the NIRS-VOT, tissue saturation (StO2) was monitored, and the rate of decrease in StO2 (Slope 1) during cuff inflation (i.e., ischemia) was quantified, as were the reperfusion magnitude (RepMAG), rate of increase in StO2 (Slope 2), and the reperfusion area under the curve (StO2AUC) following cuff deflation. Two-way (age × sex) ANOVAs were used to examine the differences in Slope 1, RepMAG, Slope 2, and StO2AUC among the YW, OW, YM, and OM. Means ± 95% CIs are reported. RESULTS: There were significant age and sex effects for Slope 1 (p = 0.01 and 0.02, respectively), which was more negative (i.e., steeper) in males versus females (-0.132±0.12 vs. -0.108±0.15 %1s-1) and in the young versus older adults (-0.133±0.13 vs. -0.107±0.14 %1s-1). There was an age effect for RepMAG (p < 0.001), which was greater in the younger than older adults (50.7±4.0 vs. 38.5±4.6%). While there was no effect of age on Slope 2, Slope 2 was steeper (p = 0.002) in males than females (1.71±0.24 vs. 1.06±0.34 %1s-1). Finally, there were age (p = 0.02) and sex (p = 0.03) main effects for StO2AUC, which was greater in males versus females (1228.5±148.8 vs. 960.1±178.9 %1s) and in the young versus older adults (1240.7±148.8 vs. 947.9±178.9 %1s). CONCLUSIONS: Overall, our results suggest that there are age and sex-related differences in skeletal muscle oxygen consumption rate and microvascular reactivity, as assessed using the NIRS-VOT technique. However, because the degree of tissue desaturation is the stimulus for subsequent reperfusion responses and the rate of desaturation was greater in the younger than older adults and in males than females, it is not clear if the differences in Slope 2 and StO2AUC reflect differences in microvascular reactivity, per se. Additional studies are needed to more fully explore this interplay.

Effect of acute nitrite infusion on contractile economy and metabolism in isolated skeletal muscle in situ during hypoxia.

Increased plasma nitrite concentrations may have beneficial effects on skeletal muscle function. The physiological basis explaining these observations has not been clearly defined and it may involve positive effects on muscle contraction force, microvascular O2 delivery and skeletal muscle oxidative metabolism. In the isolated canine gastrocnemius model, we evaluated the effects of acute nitrite infusion on muscle force and skeletal muscle oxidative metabolism. Under hypoxic conditions, but in the presence of normal convective O2 delivery, an elevated plasma nitrite concentration affects neither muscle force, nor muscle contractile economy. In accordance with previous results suggesting limited or no effects of nitrate/nitrite administrations in highly oxidative and highly perfused muscle, our data suggest that neither mitochondrial respiration, nor muscle force generation are affected by acute increased concentrations of NO precursors in hypoxia. Contrasting findings have been reported concerning the effects of augmented nitric oxide (NO) on skeletal muscle force production and oxygen consumption ( ). The present study examined skeletal muscle mitochondrial respiration and contractile economy in an isolated muscle preparation during hypoxia (but normal convective O2 delivery) with nitrite infusion. Isolated canine gastrocnemius muscles in situ (n=8) were studied during 3min of electrically stimulated isometric tetanic contractions corresponding to ∼35% of . During contractions, sodium nitrite (NITRITE) or sodium chloride (SALINE) was infused into the popliteal artery. was calculated from the Fick principle. Experiments were carried out in hypoxia ( =0.12), whereas convective O2 delivery was maintained at normal levels under both conditions by pump-driven blood flow ( ). Muscle biopsies were taken and mitochondrial respiration was evaluated by respirometry. Nitrite infusion significantly increased both nitrite and nitrate concentrations in plasma. No differences in force were observed between conditions. was not significantly different between NITRITE (6.1±1.8mL 100g-1 min-1 ) and SALINE (6.2±1.8mL100g-1 min-1 ), even after being 'normalized' per unit of developed force (muscle contractile economy). No differences between conditions were found for maximal ADP-stimulated mitochondrial respiration (both for complex I and complex II), leak respiration and oxidative phosphorylation coupling. In conclusion, in the absence of changes in convective O2 delivery, muscle force, muscle contractile economy and mitochondrial respiration were not affected by acute infusion of nitrite. The previously reported positive effects of elevated plasma nitrite concentrations are presumably mediated by the increased microvascular O2 availability.

Thenar oxygen saturation (StO2) alterations during a spontaneous breathing trial predict extubation failure

BackgroundWeaning from mechanical ventilation (MV) is a cardiovascular stress test. Monitoring the regional oxygenation status has shown promising results in predicting the tolerance to spontaneously breathe in the process of weaning from MV. Our aim was to determine whether changes in skeletal muscle oxygen saturation (StO2) measured by near-infrared spectroscopy (NIRS) on the thenar eminence during a vascular occlusion test (VOT) can be used to predict extubation failure from mechanical ventilation.MethodsWe prospectively studied 206 adult patients with acute respiratory failure receiving MV for at least 48 h from a 30-bed mixed ICU, who were deemed ready to wean by their physicians. Patients underwent a 30-min spontaneous breathing trial (SBT), and were extubated according to the local protocol. Continuous StO2 was measured non-invasively on the thenar eminence. A VOT was performed prior to and at 30 min of the SBT (SBT30). The rate of StO2 deoxygenation (DeO2), StO2 reoxygenation (ReO2) rate and StO2 hyperemic response to ischemia (HAUC) were calculated.ResultsThirty-six of the 206 patients (17%) failed their SBT. The remainder 170 patients (83%) were extubated. Twenty-three of these patients (13.5%) needed reinstitution of MV within 24 h. Reintubated patients displayed a lower HAUC at baseline, and higher relative changes in their StO2 deoxygenation rate between baseline and SBT30 (DeO2 Ratio). A logistic regression-derived StO2 score, combining baseline StO2, HAUC and DeO2 ratio, showed an AUC of 0.84 (95% CI 0.74–0.91) for prediction of extubation failure.ConclusionsExtubation failure was associated to baseline and dynamic StO2 alterations during the SBT. Monitoring StO2-derived parameters might be useful in predicting extubation outcome.