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Introduction: Regional heterogeneity of the human heart plays an important role in left ventricular (LV) and right ventricular (RV) function and may contribute to enhanced myocardial efficiency in the athlete's heart., Purpose: This study comprehensively characterized regional and transmural myocardial tissue deformation (strain) in recreationally active (RA) and endurance-trained (ET) men to determine if regional nonuniformity evolves alongside morphological adaptations associated with endurance training., Methods: Echocardiography was used to measure LV and RV global, regional (apical, mid, basal) and transmural (endocardial, epicardial) longitudinal strain in 30 endurance-trained (ET) (age, 31 ± 2 yr; body mass index, 23.1 ± 0.5 kg·m; V˙O2peak, 60.2 ± 6.5 mL·kg·min) and 30 RA (age: 29 ± 2 yr; body mass index, 23.4 ± 0.4 kg·m; V˙O2peak: 42.6 ± 4.6 mL·kg·min). Nonuniformity was characterized using apex-to-base and transmural (endocardial-to-epicardial) strain gradients., Results: Global longitudinal strain was similar in ET and RA in the left (-17.4% ± 0.4% vs -17.8% ± 0.5%, P = 0.662) and right ventricle (-25.8% ± 0.8% vs 26.4% ± 1.0%, P = 0.717). The apex-to-base strain gradient was greater in ET than RA in the left (-6.5% ± 0.7% vs -2.7% ± 0.8%, P = 0.001) and right ventricle (-9.6% ± 1.8% vs -3.0% ± 1.6%, P = 0.010). The LV transmural strain gradient was greater than RV in both groups, but similar in ET and RA (-4.7% ± 0.2% vs -4.7% ± 0.2%, P = 0.850), whereas RV transmural strain gradient was greater in ET than RA (-3.4% ± 0.3% vs -1.6% ± 0.4%, P = 0.003). RV apex-to-base and transmural strain gradients correlated with RV end-diastolic area (R = 0.536 & 0.555, respectively, P < 0.01) and V˙O2peak (R = 0.415 & 0.677, respectively, P < 0.01)., Conclusions: Transmural nonuniformity is more pronounced in the left ventricle than the RV free wall; however, RV functional nonuniformity develops markedly after endurance training. Differences in myocardial architecture and exercise-induced wall stress in the left and right ventricles are possible explanations for the marked functional nonuniformity throughout the myocardium and in response to endurance exercise training.

It remains incompletely understood whether there is an association between the transcriptome profiles of skeletal muscle and blood leukocytes in response to exercise or other physiological stressors. We have previously analyzed the changes in the muscle and blood neutrophil transcriptome in eight trained men before and 3, 48, and 96 h after 2 h cycling and running. Because we collected muscle and blood in the same individuals and under the same conditions, we were able to directly compare gene expression between the muscle and blood neutrophils. Applying weighted gene coexpression network analysis (WGCNA) as an advanced network-driven method to these original data sets enabled us to compare the muscle and neutrophil transcriptomes in a rigorous and systematic manner. Two gene networks were identified that were preserved between skeletal muscle and blood neutrophils, functionally related to mitochondria and posttranslational processes. Strong preservation measures ( Z summary > 10) for both muscle-neutrophil gene networks were evident within the postexercise recovery period. Muscle and neutrophil gene coexpression was strongly correlated in the mitochondria-related network ( r = 3.17E-2). We also identified multiple correlations between muscular gene subnetworks and exercise-induced changes in blood leukocyte counts, inflammation, and muscle damage markers. These data reveal previously unidentified gene coexpression between skeletal muscle and blood neutrophils following exercise, showing the value of WGCNA to understand exercise physiology. Furthermore, these findings provide preliminary evidence in support of the notion that blood neutrophil gene networks may potentially help us to track physiological and pathophysiological changes in the muscle. P By using weighted gene coexpression network analysis, an advanced bioinformatics method, we have identified previously unknown, functional gene networks that are preserved between skeletal muscle and blood neutrophils during recovery from exercise. These novel preliminary data suggest that muscular gene networks are coexpressed in blood leukocytes following physiological stress. This is a step forward toward the development of blood neutrophil gene subnetworks as part of blood biomarker panels to assess muscle health and disease.NEW & NOTEWORTHY By using weighted gene coexpression network analysis, an advanced bioinformatics method, we have identified previously unknown, functional gene networks that are preserved between skeletal muscle and blood neutrophils during recovery from exercise. These novel preliminary data suggest that muscular gene networks are coexpressed in blood leukocytes following physiological stress. This is a step forward toward the development of blood neutrophil gene subnetworks as part of blood biomarker panels to assess muscle health and disease., (Copyright © 2017 the American Physiological Society.)

Background: The purpose of the present study was to investigate the effects of regular treadmill walking on plasma factors that increase low-shear blood viscosity and red blood cell aggregation in older women with type 2 diabetes., Methods: Eighteen women with type 2 diabetes (age: 69±3 yr; body mass index: 30.5±5.0 kg⋅m-2) performed 12-wk of 120 min⋅wk-1 of supervised treadmill walking at an intensity equivalent to the gas-exchange threshold. Peak exercise values, anthropometry and blood indices of diabetic status, markers of inflammation, and plasma fibrinogen were analysed during a 6-wk pre-training 'control' period, and then after 6 and 12-wk of regular walking., Results: Regular walking significantly increased peak oxygen uptake (p = 0.01). Body mass, waist to hip ratio, and glycaemic control did not change. Systolic and diastolic blood pressures decreased by 8.5% (p < 0.01) and 7.2% (p < 0.01) respectively, cholesterol to high-density lipoprotein (HDL) ratio decreased by 9.6% (p = 0.01), and HDL concentration significantly increased (p = 0.01). While 12 wk of regular walking did not significantly alter plasma concentrations of interleukin-6 (IL-6), tumour necrosis factor-α, or C-reactive protein, plasma fibrinogen concentration decreased by 6.9% (p < 0.01) and plasma interleukin-10 (IL-10) concentration increased from 1.15±0.32 to 1.62±0.22 mmol⋅L-1 (p < 0.04)., Conclusions: Improved plasma inflammatory profile and decreased plasma fibrinogen concentration is induced by regular walking, independent of glycaemic control. These factors may mediate the improved haemorheology associated with exercise training in metabolic disorders.

Key Points: Strenuous endurance exercise induces transient functional and biochemical cardiac perturbations that persist for 24-48 h. The magnitude and time-course of exercise-induced reductions in ventricular function and increases in cardiac injury markers are influenced by the intensity and duration of exercise. In a human experimental model, exercise-induced reductions in ventricular strain and increases in cardiac troponin are greater, and persist for longer, when exercise is performed within the heavy- compared to moderate-intensity exercise domain, despite matching for total mechanical work. The results of the present study help us better understand the dose-response relationship between endurance exercise and acute cardiac stress/injury, a finding that has implications for the prescription of day-to-day endurance exercise regimes., Abstract: Strenuous endurance exercise induces transient cardiac perturbations with ambiguous health outcomes. The present study investigated the magnitude and time-course of exercise-induced functional and biochemical cardiac perturbations by manipulating the exercise intensity-duration matrix. Echocardiograph-derived left (LV) and right (RV) ventricular global longitudinal strain (GLS), and serum high-sensitivity cardiac troponin (hs-cTnI) concentration, were examined in 10 males (age: 27 ± 4 years; V̇O2, peak : 4.0 ± 0.8 l min(-1) ) before, throughout (50%, 75% and 100%), and during recovery (1, 3, 6 and 24 h) from two exercise trials. The two exercise trials consisted of 90 and 120 min of heavy- and moderate-intensity cycling, respectively, with total mechanical work matched. LVGLS decreased (P < 0.01) during the 90 min trial only, with reductions peaking at 1 h post (pre: -19.9 ± 0.6%; 1 h post: -18.5 ± 0.7%) and persisting for >24 h into recovery. RVGLS decreased (P < 0.05) during both exercise trials with reductions in the 90 min trial peaking at 1 h post (pre: -27.5 ± 0.7%; 1 h post: -25.1 ± 0.8%) and persisting for >24 h into recovery. Serum hs-cTnI increased (P < 0.01) during both exercise trials, with concentrations peaking at 3 h post but only exceeding cardio-healthy reference limits (14 ng l(-1) ) in the 90 min trial (pre: 4.2 ± 2.4 ng l(-1) ; 3 h post: 25.1 ± 7.9 ng l(-1) ). Exercise-induced reductions in ventricular strain and increases in cardiac injury markers persist for 24 h following exercise that is typical of day-to-day endurance exercise training; however, the magnitude and time-course of this response can be altered by manipulating the intensity-duration matrix., (© 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.)

Reprogramming of gene expression is fundamental for skeletal muscle adaptations in response to endurance exercise. This study investigated the time course-dependent changes in the muscular transcriptome after an endurance exercise trial consisting of 1 h of intense cycling immediately followed by 1 h of intense running. Skeletal muscle samples were taken at baseline, 3 h, 48 h, and 96 h postexercise from eight healthy, endurance-trained men. RNA was extracted from muscle. Differential gene expression was evaluated using Illumina microarrays and validated with qPCR. Gene set enrichment analysis identified enriched molecular signatures chosen from the Molecular Signatures Database. Three hours postexercise, 102 gene sets were upregulated [family wise error rate (FWER), P < 0.05], including groups of genes related with leukocyte migration, immune and chaperone activation, and cyclic AMP responsive element binding protein (CREB) 1 signaling. Forty-eight hours postexercise, among 19 enriched gene sets (FWER, P < 0.05), two gene sets related to actin cytoskeleton remodeling were upregulated. Ninety-six hours postexercise, 83 gene sets were enriched (FWER, P < 0.05), 80 of which were upregulated, including gene groups related to chemokine signaling, cell stress management, and extracellular matrix remodeling. These data provide comprehensive insights into the molecular pathways involved in acute stress, recovery, and adaptive muscular responses to endurance exercise. The novel 96 h postexercise transcriptome indicates substantial transcriptional activity potentially associated with the prolonged presence of leukocytes in the muscles. This suggests that muscular recovery, from a transcriptional perspective, is incomplete 96 h after endurance exercise involving muscle damage.

Impaired O2 transport to skeletal muscle potentially contributes to the decline in aerobic capacity with aging. Thus, we examined whether (1) skeletal muscle oxidative capacity decreases with age and (2) O2 availability or mitochondrial capacity limits the maximal rate of mitochondrial ATP synthesis in vivo in sedentary elderly individuals. We used (31)P-magnetic resonance spectroscopy ((31)P-MRS) to examine the PCr recovery kinetics in six young (26 ± 10 years) and six older (69 ± 3 years) sedentary subjects following 4 min of dynamic plantar flexion exercise under different fractions of inspired O2 (FiO2, normoxia 0.2; hyperoxia 1.0). End-exercise pH was not significantly different between old (7.04 ± 0.10) and young (7.05 ± 0.04) and was not affected by breathing hyperoxia (old 7.08 ± 0.08, P > 0.05 and young 7.05 ± 0.03). Likewise, end-exercise PCr was not significantly different between old (19 ± 4 mM) and young (24 ± 5 mM) and was not changed in hyperoxia. The PCr recovery time constant was significantly longer in the old (36 ± 9 s) compared to the young in normoxia (23 ± 8 s, P < 0.05) and was not significantly altered by breathing hyperoxia in both the old (35 ± 9 s) and young (29 ± 10 s) groups. Therefore, this study reveals that the muscle oxidative capacity of both sedentary young and old individuals is independent of O2 availability and that the decline in oxidative capacity with age is most likely due to limited mitochondrial content and/or mitochondrial dysfunction and not O2 availability.

Neutrophils serve as an intriguing model for the study of innate immune cellular activity induced by physiological stress. We measured changes in the transcriptome of circulating neutrophils following an experimental exercise trial (EXTRI) consisting of 1 h of intense cycling immediately followed by 1 h of intense running. Blood samples were taken at baseline, 3 h, 48 h, and 96 h post-EXTRI from eight healthy, endurance-trained, male subjects. RNA was extracted from isolated neutrophils. Differential gene expression was evaluated using Illumina microarrays and validated with quantitative PCR. Gene set enrichment analysis identified enriched molecular signatures chosen from the Molecular Signatures Database. Blood concentrations of muscle damage indexes, neutrophils, interleukin (IL)-6 and IL-10 were increased (P < 0.05) 3 h post-EXTRI. Upregulated groups of functionally related genes 3 h post-EXTRI included gene sets associated with the recognition of tissue damage, the IL-1 receptor, and Toll-like receptor (TLR) pathways (familywise error rate, P value < 0.05). The core enrichment for these pathways included TLRs, low-affinity immunoglobulin receptors, S100 calcium binding protein A12, and negative regulators of innate immunity, e.g., IL-1 receptor antagonist, and IL-1 receptor associated kinase-3. Plasma myoglobin changes correlated with neutrophil TLR4 gene expression (r = 0.74; P < 0.05). Neutrophils had returned to their nonactivated state 48 h post-EXTRI, indicating that their initial proinflammatory response was transient and rapidly counterregulated. This study provides novel insight into the signaling mechanisms underlying the neutrophil responses to endurance exercise, suggesting that their transcriptional activity was particularly induced by damage-associated molecule patterns, hypothetically originating from the leakage of muscle components into the circulation.

To better understand the metabolic implications of a higher ATP cost of contraction in chronic obstructive pulmonary disease (COPD), we used (31)P-magnetic resonance spectroscopy ((31)P-MRS) to examine muscle energetics and pH in response to graded exercise. Specifically, in six patients and six well-matched healthy controls, we determined the intracellular threshold for pH (T(pH)) and inorganic phosphate-to-phosphocreatine ratio (T(Pi/PCr)) during progressive dynamic plantar flexion exercise with work rate expressed as both absolute and relative intensity. Patients with COPD displayed a lower peak power output (WRmax) compared with controls (controls 25 ± 4 W, COPD 15 ± 5 W, P = 0.01) while end-exercise pH (controls 6.79 ± 0.15, COPD 6.76 ± 0.21, P = 0.87) and PCr consumption (controls 82 ± 10%, COPD 70 ± 18%, P = 0.26) were similar between groups. Both T(pH) and T(Pi/PCr) occurred at a significantly lower absolute work rate in patients with COPD compared with controls (controls: 14.7 ± 2.4 W for T(pH) and 15.3 ± 2.4 W for T(Pi/PCr); COPD: 9.7 ± 4.5 W for T(pH) and 10.0 ± 4.6 W for T(Pi/PCr), P < 0.05), but these thresholds occurred at the same percentage of WRmax (controls: 63 ± 11% WRmax for T(pH) and 67 ± 18% WRmax for T(Pi/PCr); COPD: 59 ± 9% WRmax for T(pH) and 61 ± 12% WRmax for T(Pi/PCr), P > 0.05). Indexes of mitochondrial function, the PCr recovery time constant (controls 42 ± 7 s, COPD 45 ± 11 s, P = 0.66) and the PCr resynthesis rate (controls 105 ± 21%/min, COPD 91 ± 31%/min, P = 0.43) were similar between groups. In combination, these results reveal that when energy demand is normalized to WRmax, as a consequence of higher ATP cost of contraction, patients with COPD display the same metabolic pattern as healthy subjects, suggesting that skeletal muscle energy production is well preserved in these patients.

Heart rate variability (HRV) and haemorheology adaptations to 12 wk of varied-dose treadmill walking were investigated in women aged 65-74 yr with type 2 diabetes. Subjects were randomly allocated into two groups where exercise frequency and session duration were manipulated (Group 1: 2 × 60 min·wk(-1) or Group 2: 4 × 30 min·wk(-1)), but intensity and accumulated weekly duration of exercise were consistent between groups (100% gas-exchange threshold; 120 min·wk(-1)). Twelve weeks of exercise training significantly improved peak oxygen uptake, time to exhaustion, and gas-exchange threshold (p < 0.05), independent of exercise group. Exercise training did not significantly change glycaemic control or body mass. Red blood cell (RBC) aggregation and RBC deformability significantly decreased (p < 0.05) for both groups. No change in HRV was observed for Group 1, whereas several key indicators of HRV were significantly improved in Group 2 (p < 0.05). The present study was the first to report decreased RBC aggregation following an exercise-only intervention and that exercise training improved RBC aggregation without a concomitant improvement in glycaemic control. The accumulated weekly exercise duration may be the most important training component for the prescription of exercise in older women with type 2 diabetes.

The contribution of respiratory muscle O2 uptake ((.)V(O2RM)) to the development of the slow component of O2 uptake kinetics ((.)V(O2SC)) is unclear. The aim of the present study was to examine the impact of respiratory muscle unloading (via breathing, a He-O2 mixture) on the amplitude of (.)V(O2SC) during exercise performed below (B-RCT) and above the respiratory compensation threshold (A-RCT). We hypothesized that breathing He-O2 would reduce the amplitude of the (.)V(O2SC) by a greater amount during exercise performed A-RCT than B-RCT. Eight healthy male recreational cyclists performed constant load cycling in four sets of conditions: (1) B-RCT breathing normal air; (2) B-RCT breathing He-O2; (3) A-RCT breathing normal air; and (4) A-RCT breathing He-O2. Breathing He-O2 did not significantly attenuate the (.)V(O2SC) during exercise performed B-RCT (-3+/-14%, P >0.05). However, breathing He-O2 significantly reduced the (.)V(O2SC) during exercise A-RCT(-45+/-6%, P <0.05). The attenuated (.)V(O2SC) while breathing He-O2 is likely to reflect a decreased (.)V(O2RM). Minute ventilation was not +/-different between normal air and He-O2 breathing trials either B-RCT or A-RCT. However, operating lung volume was significantly lower when breathing He-O2 during exercise performed A-RCT (-12+/-3%, P <0.05). These findings suggest that (.)V(O2RM) comprises a greater proportion of the (.)V(O2SC) when exercise is performed A-RCT compared with B-RCT. Therefore, the impact of breathing He-O2 was more pronounced during exercise A-RCT. Furthermore, changes in operating lung volume and the work of breathing appear to play an important role in the development of the (.)V(O2SC).

31P-magnetic resonance spectroscopy was used to study phosphocreatine (PCr) onset kinetics in exercising human gastrocnemius muscle under varied fractions of inspired O(2) (F(IO(2))). Five male subjects performed three identical work bouts (5 min duration; order randomised) at a submaximal workload while breathing 0.1, 0.21 or 1.0 F(IO(2)). Either a single or double exponential model was fitted to the PCr kinetics. The phase I tau (0.1, 38.6 +/- 7.5; 0.21, 34.5 +/- 7.9; 1.0, 38.6 +/- 9.2 s) and amplitude, A(1) (0.1, 0.34 +/- 0.03; 0.21, 0.28 +/- 0.05; 1.0, 0.28 +/- 0.03,% fall in PCr) were invariant (both P > 0.05) across F(IO(2)) trials. The initial rate of change in PCr hydrolysis at exercise onset, calculated as A(1)/tau(1) (%PCr reduction s(-1)), was the same across F(IO(2)) trials. A PCr slow component (phase II) was present at an F(IO(2)) of 0.1 and 0.21; however, breathing 1.0 F(IO(2)) ablated the slow component. The onset of the slow component resulted in a greater (P< or = 0.05) overall percentage fall in PCr (both phase I and II) as F(IO(2)) decreased (0.43 +/- 0.05, 0.34 +/- 0.05, 0.28 +/- 0.03) for 0.1, 0.21 and 1.0 F(IO(2)), respectively. These data demonstrate that altering F(IO(2)) does not affect the initial phase I PCr onset kinetics, which supports the notion that O(2) driving pressure does not limit PCr kinetics at the onset of submaximal exercise. Thus, these data imply that the manner in which microvascular and intracellular P(O(2)) regulates PCr hydrolysis in exercising muscle is not due to the initial kinetic fall in PCr at exercise onset.

Strenuous exercise elicits transient functional and biochemical cardiac imbalances. Yet, the extent to which these responses are altered owing to aging is unclear. Accordingly, echocardiograph-derived left ventricular (LV) and right ventricular (RV) global longitudinal strain (GLS) and high-sensitivity cardiac troponin I (hs-cTnI) were assessed before (pre) and after (post) a 60-min high-intensity cycling race intervention (CRIT60) in 11 young (18-30 yr) and 11 middle-aged (40-65 yr) highly trained male cyclists, matched for cardiorespiratory fitness. LV and RV GLS were measured at rest and during a semirecumbent exercise challenge performed at the same intensity (young: 93 ± 10; middle-aged: 85 ± 11W, P = 0.60) pre- and post-CRIT60. Augmentation (change from rest-to-exercise challenge) of LV GLS (pre: -2.97 ± 0.65; post: -0.82 ± 0.48%, P = 0.02) and RV GLS (pre: -2.08 ± 1.28; post: 3.08 ± 2.02%, P = 0.01) was attenuated and completely abolished, in the young following CRIT60, while augmentation of LV GLS (pre: -3.21 ± 0.41; post: -3.99 ± 0.55%, P = 0.22) and RV GLS (pre: -3.47 ± 1.44; post: -1.26 ± 1.00%, P = 0.27) was preserved in middle-aged following CRIT60. While serum hs-cTnI concentration increased followingCRIT60 in the young (pre: 7.3 ± 1.6; post: 17.7 ± 1.6 ng/L, P < 0.01) and middle-aged (pre: 4.5 ± 0.6; post: 10.7 ± 2.0 ng/L, P < 0.01), serum hs-cTnI concentration increased to a greater extent in the young than in the middle-aged following CRIT60 (P < 0.01). These findings suggest that functional and biochemical cardiac perturbations induced by high-intensity exercise are attenuated in middle-aged relative to young individuals. Further study is warranted to determine whether acute exercise-induced cardiac perturbations alter the adaptive myocardial remodeling response. NEW & NOTEWORTHY High-intensity endurance exercise elicits acute cardiac imbalances that may be an important stimulus for adaptive cardiac remodeling. This study highlights that following a bout of high-intensity exercise that is typical of routine day-today cycling training, exercise-induced autonomic, biochemical, and functional cardiac imbalances are attenuated in middle-aged relative to young well-trained cyclists. These findings suggest that aging may alter exercise-induced stress stimulus response that initiates cardiac remodeling in athlete's heart. [ABSTRACT FROM AUTHOR]

Exercise triggers hormesis, conditioning hearts against damaging consequences of subsequent ischemia- reperfusion (I/R). We test whether "low-stress" voluntary activity modifies I/R tolerance and molecular determinants of cardiac survival. Male C57BL/6 mice were provided 7-day access to locked (7SED) or rotating (7EX) running-wheels before analysis of cardiac prosurvival (Akt, ERK 1/2) and prodeath (GSK3β) kinases, transcriptomic adaptations, and functional tolerance of isolated hearts to 25-min ischemia/ 45-min reperfusion. Over 7 days, 7EX mice increased running from 2.1 ± 0.2 to 5.3 ± 0.3 km/day (mean speed 38 ± 2 m/min), with activity improving myocardial I/R tolerance: 7SED hearts recovered 43 ± 3% of ventricular force with diastolic contracture of 33 ± 3 mmHg, whereas 7EX hearts recovered 63 ± 5% of force with diastolic dysfunction reduced to 23 ± 2 mmHg (P < 0.05). Cytosolic expression (total protein) of Akt and GSK3β was unaltered, while ERK 1/2 increased 30% in 7EX vs. 7SED hearts. Phosphorylation of Akt and ERK 1/2 was unaltered, whereas GSK3β phosphorylation increased ~90%. Microarray interrogation identified significant changes (≥1.3-fold expression change, ≤5% FDR) in 142 known genes, the majority (92%) repressed. Significantly modified paths/ networks related to inflammatory/immune function (particularly interferon- dependent), together with cell movement, growth, and death. Of only 14 induced transcripts, 3 encoded interrelated sarcomeric proteins titin, α-actinin, and myomesin-2, while transcripts for protective actin-stabilizing ND1-L and activator of mitochondrial biogenesis ALAS1 were also induced. There was no transcriptional evidence of oxidative heat-shock or other canonical "stress" responses. These data demonstrate that relatively brief voluntary activity substantially improves cardiac ischemic tolerance, an effect independent of shifts in Akt, but associated with increased total ERK 1/2 and phospho-inhibition of GSK3β. Transcriptomic data implicate inflammatory/immune and sarcomeric modulation in activity-dependent protection. [ABSTRACT FROM AUTHOR]

Impaired metabolism in peripheral skeletal muscles potentially contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). We used 31P-magnetic resonance spectroscopy (31P-MRS) to examine the energy cost and skeletal muscle energetics in six patients with COPD during dynamic plantar flexion exercise compared with six well-matched healthy control subjects. Patients with COPD displayed a higher energy cost of muscle contraction compared with the controls (control: 6.1 ± 3.1% of rest·min-1·W-1, COPD: 13.6 ± 8.3% of rest·min-1·W-1, P = 0.01). Although, the initial phosphocreatine resynthesis rate was also significantly attenuated in patients with COPD compared with controls (control: 74 ± 17% of rest/min, COPD: 52 ± 13% of rest/min, P = 0.04), when scaled to power output, oxidative ATP synthesis was similar between groups (6.5 ± 2.3% of rest·min-1·W-1 in control and 7.8 ± 3.9% of rest·min-1·W-1 in COPD, P = 0.52). Therefore, our results reveal, for the first time that in a small subset of patients with COPD a higher ATP cost of muscle contraction may substantially contribute to the lower mechanical efficiency previously reported in this population. In addition, it appears that some patients with COPD have preserved mitochondrial function and normal energy supply in lower limb skeletal muscle. [ABSTRACT FROM AUTHOR]

The contribution of respiratory muscle O2 uptake to the development of the slow component of O2 uptake kinetics is unclear. The aim of the present study was to examine the impact of respiratory muscle unloading (via breathing, a He–O2 mixture) on the amplitude of during exercise performed below (B-RCT) and above the respiratory compensation threshold (A-RCT). We hypothesized that breathing He–O2 would reduce the amplitude of the by a greater amount during exercise performed A-RCT than B-RCT. Eight healthy male recreational cyclists performed constant-load cycling in four sets of conditions: (1) B-RCT breathing normal air; (2) B-RCT breathing He–O2; (3) A-RCT breathing normal air; and (4) A-RCT breathing He–O2. Breathing He–O2 did not significantly attenuate the during exercise performed B-RCT (–3 ± 14%, P > 0.05). However, breathing He–O2 significantly reduced the during exercise A-RCT (–45 ± 6%, P < 0.05). The attenuated while breathing He–O2 is likely to reflect a decreased . Minute ventilation was not different between normal air and He–O2 breathing trials either B-RCT or A-RCT. However, operating lung volume was significantly lower when breathing He–O2 during exercise performed A-RCT (–12 ± 3%, P < 0.05). These findings suggest that comprises a greater proportion of the when exercise is performed A-RCT compared with B-RCT. Therefore, the impact of breathing He–O2 was more pronounced during exercise A-RCT. Furthermore, changes in operating lung volume and the work of breathing appear to play an important role in the development of the . [ABSTRACT FROM AUTHOR]

In contrast to their exercise-trained counterparts, the maximal oxidative rate of skeletal muscle in sedentary humans appears not to benefit from supplemental O2 availability but is impacted by severe hypoxia, suggesting a metabolic limitation either at or below ambient O2 levels. However, the critical level of O2 availability at which maximal metabolic rate is reduced in sedentary humans is unknown. Using 31P magnetic resonance spectroscopy and arterial oximetry, phosphocreatine (PCr) recovery kinetics and arterial oxygenation were assessed in six sedentary subjects performing 5-mm bouts of plantar flexion exercise followed by 6 mm of recovery. Each trial was repeated while breathing one of four different fractions of inspired O2 (FIO2) (0.10, 0.12, 0.15, and 0.21). The PCr recovery rate constant (a marker of oxidative capacity) was unaffected by reductions in FIO2, remaining at a value of 1.5 ± 0.2 min-1 until arterial O2 saturation (SaO2) fell to less than ∼92%, the average value reached breathing an FIO2 of 0.15. Below this SaO2, the PCr rate constant fell significantly by 13 and 31% to 1.3 ± 0.2 and 1.0 ± 0.2 min-1 (P < 0.05) as SaO2 was reduced to 82 ± 3 and 77 ± 2%, respectively. In conclusion, this study has revealed that O2 availability does not impact maximal oxidative rate in sedentary humans until the O2 level falls well below that of ambient air, indicating a metabolic limitation in normoxia. [ABSTRACT FROM AUTHOR]

Previously, it was demonstrated in exercise-trained humans that phosphocreatine (PCr) recovery is significantly altered by fraction of inspired O2 (FIO2), suggesting that in this population under normoxic conditions, O2 availability limits maximal oxidative rate. Haseler LJ, Hogan ML, and Richardson RS. J Appl Physiol 86: 2013-2018, 1999. To further elucidate these population-specific limitations to metabolic rate, we used 31P-magnetic resonance spectroscopy to study the exercising human gastrocnemius muscle under conditions of varied FIO2 in sedentary subjects. To test the hypothesis that PCr recovery from submaximal exercise in sedentary subjects is not limited by O2 availability, but rather by their mitochondrial capacity, six sedentary subjects performed three bouts of 6-min steady-state submaximal plantar flexion exercise followed by 5 min of recovery while breathing three different FIO2 (0.10, 0.21, and 1.00). PCr recovery time constants were significantly longer in hypoxia (47.0 ± 3.2 s), but there was no difference between hyperoxia (31.8 ± 1.9 s) and normoxia (30.0 ± 2.1 s) (mean ± SE). End-exemise pH was not significantly different across treatments. These results suggest that the maximal muscle oxidative rate of these sedentary subjects, unlike their exercise-trained counterparts, is limited by mitochondrial capacity and not O2 availability in normoxia. Additionally, the significant elongation of PCr recovery in these subjects in hypoxia illustrates the reliance on O2 supply at the other end of the O2 availability spectrum in both sedentary and active populations. [ABSTRACT FROM AUTHOR]

31P-magnetic resonance spectroscopy was used to study phosphocreatine (PCr) onset kinetics in exercising human gastrocnemius muscle under varied fractions of inspired 02 (FIO2). Five male subjects performed three identical work bouts (5 min duration; order randomised) at a submaximal workload while breathing 0.1, 0.21 or 1.0 FIO2. Either a single or double exponential model was fitted to the PCr kinetics. The phase I τ (0.1, 38.6 ± 7.5; 0.21, 34.5 ± 7.9; 1.0, 38.6 ± 9.2 s) and amplitude, A1 (0.1, 0.34 ± 0.03; 0.21, 0.28 ± 0.05; 1.0, 0.28 ± 0.03,% fall in PCr) were invariant (both P > 0.05) across FIO2 trials. The initial rate of change in PCr hydrolysis at exercise onset, calculated as A1/τ1 (%PCr reduction s-1), was the same across FIO2 trials. A PCr slow component (phase II) was present at an FIO2 of 0.1 and 0.21; however, breathing 1.0 FIO2 ablated the slow component. The onset of the slow component resulted in a greater (P ≤ 0.05) overall percentage fall in PCr (both phase I and II) as FIO2 decreased (0.43 ± 0.05, 0.34 ± 0.05, 0.28 ± 0.03) for 0.1, 0.21 and 1.0 FIO2, respectively. These data demonstrate that altering FIO2 does not affect the initial phase I PCr onset kinetics, which supports the notion that O2 driving pressure does not limit PCr kinetics at the onset of submaximal exercise. Thus, these data imply that the manner in which microvascular and intracellular PO2 regulates PCr hydrolysis in exercising muscle is not due to the initial kinetic fall in PCr at exercise onset. [ABSTRACT FROM AUTHOR]

Exercise is cardioprotective, though optimal interventions are unclear. We assessed duration dependent effects of exercise on myocardial ischemia-reperfusion (I-R) injury, kinase signaling and gene expression. Responses to brief (2 day; 2EX), intermediate (7 and 14 day; 7EX and 14EX) and extended (28 day; 28EX) voluntary wheel running (VWR) were studied in male C57Bl/6 mice. Cardiac function, I-R tolerance and survival kinase signaling were assessed in perfused hearts. Mice progressively increased running distances and intensity, from 2.4 ± 0.2 km/day (0.55 ± 0.04 m/s) at 2-days to 10.6 ± 0.4 km/day (0.72 ± 0.06 m/s) after 28-days. Myocardial mass and contractility were modified at 14–28 days VWR. Cardioprotection was not 'dose-dependent', with I-R tolerance enhanced within 7 days and not further improved with greater VWR duration, volume or intensity. Protection was associated with AKT, ERK1/2 and GSK3β phosphorylation, with phospho-AMPK selectively enhanced with brief VWR. Gene expression was duration-dependent: 7 day VWR up-regulated glycolytic (Pfkm) and down-regulated maladaptive remodeling (Mmp2) genes; 28 day VWR up-regulated caveolar (Cav3), mitochondrial biogenesis (Ppargc1a , Sirt3) and titin (Ttn) genes. Interestingly, I-R tolerance in 2EX/2SED groups improved vs. groups subjected to longer sedentariness, suggesting transient protection on transition to housing with running wheels. Cardioprotection is induced with as little as 7 days VWR, yet not enhanced with further or faster running. This protection is linked to survival kinase phospho-regulation (particularly AKT and ERK1/2), with glycolytic, mitochondrial, caveolar and myofibrillar gene changes potentially contributing. Intriguingly, environmental enrichment may also protect via similar kinase regulation. [ABSTRACT FROM AUTHOR]