Role of skeletal muscles impairment and brain oxygenation in limiting oxidative metabolism during exercise after bed rest

2010 ◽  
Vol 109 (1) ◽  
pp. 101-111 ◽  
Author(s):  
Simone Porcelli ◽  
Mauro Marzorati ◽  
Francesca Lanfranconi ◽  
Paola Vago ◽  
Rado Pišot ◽  
...  

“Central” and “peripheral” limitations to oxidative metabolism during exercise were evaluated in 10 young males following a 35-day horizontal bed rest (BR). Incremental exercise (IE) and moderate- and heavy-intensity constant-load exercises (CLE) were carried out on a cycloergometer before and 1–2 days after BR. Pulmonary gas exchange, cardiac output (Q̇; by impedance cardiography), skeletal muscle (vastus lateralis), and brain (frontal cortex) oxygenation (by near-infrared spectroscopy) were determined. After BR, “peak” (values at exhaustion during IE) workload, peak O2 uptake (V̇o2peak), peak stroke volume, Q̇peak, and peak skeletal muscle O2 extraction were decreased (−18, −18, −22, −19, and −33%, respectively). The gas exchange threshold was ∼60% of V̇o2peak both before and after BR. At the highest workloads, brain oxygenation data suggest an increased O2 extraction, which was unaffected by BR. V̇o2 kinetics during CLE (same percentage of peak workload before and after BR) were slower (time constant of the “fundamental” component: 31.1 ± 2.0 s before vs. 40.0 ± 2.2 s after BR); the amplitude of the “slow component” was unaffected by BR, thus it would be greater, after BR, at the same absolute workload. A more pronounced “overshoot” of skeletal muscle O2 extraction during CLE was observed after BR, suggesting an impaired adjustment of skeletal muscle O2 delivery. The role of skeletal muscles in the impairment of oxidative metabolism during submaximal and maximal exercise after BR was identified. The reduced capacity of peak cardiovascular O2 delivery did not determine a “competition” for the available O2 between skeletal muscles and brain.

2010 ◽  
Vol 299 (5) ◽  
pp. R1298-R1305 ◽  
Author(s):  
Desy Salvadego ◽  
Stefano Lazzer ◽  
Carlo Busti ◽  
Raffaela Galli ◽  
Fiorenza Agosti ◽  
...  

A functional evaluation of skeletal muscle oxidative metabolism was performed in a group of obese adolescents (OB). The various components of pulmonary O2 uptake (V̇o2) kinetics were evaluated during 10-min constant-load exercises (CLE) on a cycloergometer at different percentages of V̇o2max. The relationships of these components with the gas exchange threshold (GET) were determined. Fourteen male OB [age 16.5 ± 1.0 (SD) yr, body mass index 34.5 ± 3.1 kg·m−2] and 13 normal-weight, age-matched nonathletic male volunteers (control group) were studied. The time-constant (τf) of the fundamental component and the presence, pattern, and relative amplitude of the slow component of V̇o2 kinetics were determined at 40, 60, and 80% of V̇o2max, previously estimated during an incremental test. V̇o2max (l/min) was similar in the two groups. GET was lower in OB (55.7 ± 6.7% of V̇o2max) than in control (65.1 ± 5.2%) groups. The τf was higher in OB subjects, indicating a slower fundamental component. At CLE 60% (above GET in OB subjects, below GET in control subjects) a slow component was observed in nine out of fourteen OB subjects, but none in the control group. All subjects developed a slow component at CLE 80% (above GET in both OB and control). Twelve OB subjects did not complete the 10-min CLE 80% due to voluntary exhaustion. In nine OB subjects, the slow component was characterized by a linear increase in V̇o2 as a function of time. The slope of this increase was inversely related to the time to exhaustion. The above findings should negatively affect exercise tolerance in obese adolescents and suggest an impairment of skeletal muscle oxidative metabolism. Also in obese adolescents, exercise evaluation and prescription at submaximal loads should be done with respect to GET and not at a given percentage of V̇o2max.


2011 ◽  
Vol 111 (6) ◽  
pp. 1719-1726 ◽  
Author(s):  
Desy Salvadego ◽  
Stefano Lazzer ◽  
Mauro Marzorati ◽  
Simone Porcelli ◽  
Enrico Rejc ◽  
...  

A functional evaluation of skeletal muscle oxidative metabolism during dynamic knee extension (KE) incremental exercises was carried out following a 35-day bed rest (BR) (Valdoltra 2008 BR campaign). Nine young male volunteers (age: 23.5 ± 2.2 yr; mean ± SD) were evaluated. Pulmonary gas exchange, heart rate and cardiac output (by impedance cardiography), skeletal muscle (vastus lateralis) fractional O2 extraction, and brain (frontal cortex) oxygenation (by near-infrared spectroscopy) were determined during incremental KE. Values at exhaustion were considered “peak”. Peak heart rate (147 ± 18 beats/min before vs. 146 ± 17 beats/min after BR) and peak cardiac output (17.8 ± 3.3 l/min before vs. 16.1 ± 1.8 l/min after BR) were unaffected by BR. As expected, brain oxygenation did not decrease during KE. Peak O2 uptake was lower after vs. before BR, both when expressed as liters per minute (0.99 ± 0.17 vs. 1.26 ± 0.27) and when normalized per unit of quadriceps muscle mass (46.5 ± 6.4 vs. 56.9 ± 11.0 ml·min−1·100 g−1). Skeletal muscle peak fractional O2 extraction, expressed as a percentage of the maximal values obtained during a transient limb ischemia, was lower after (46.3 ± 12.1%) vs. before BR (66.5 ± 11.2%). After elimination, by the adopted exercise protocol, of constraints related to cardiovascular O2 delivery, a decrease in peak O2 uptake and muscle peak capacity of fractional O2 extraction was found after 35 days of BR. These findings suggest a substantial impairment of oxidative function at the muscle level, “downstream” with respect to bulk blood flow to the exercising muscles, that is possibly at the level of blood flow distribution/O2 utilization inside the muscle, peripheral O2 diffusion, and intracellular oxidative metabolism.


1997 ◽  
Vol 352 (1354) ◽  
pp. 677-683 ◽  
Author(s):  
M. Ferrari ◽  
T. Binzoni ◽  
V. Quaresima

Oxidative metabolism is the dominant source of energy for skeletal muscle. Near–infrared spectroscopy allows the non–invasive measurement of local oxygenation, blood flow and oxygen consumption. Although several muscle studies have been made using various near–infrared optical techniques, it is still difficult to interpret the local muscle metabolism properly. The main findings of near–infrared spectroscopy muscle studies in human physiology and clinical medicine are summarized. The advantages and problems of near–infrared spectroscopy measurements, in resting and exercising skeletal muscles studies, are discussed through some representative examples.


2007 ◽  
Vol 293 (5) ◽  
pp. R2059-R2069 ◽  
Author(s):  
Steven D. Mason ◽  
Helene Rundqvist ◽  
Ioanna Papandreou ◽  
Roger Duh ◽  
Wayne J. McNulty ◽  
...  

During endurance training, exercising skeletal muscle experiences severe and repetitive oxygen stress. The primary transcriptional response factor for acclimation to hypoxic stress is hypoxia-inducible factor-1α (HIF-1α), which upregulates glycolysis and angiogenesis in response to low levels of tissue oxygenation. To examine the role of HIF-1α in endurance training, we have created mice specifically lacking skeletal muscle HIF-1α and subjected them to an endurance training protocol. We found that only wild-type mice improve their oxidative capacity, as measured by the respiratory exchange ratio; surprisingly, we found that HIF-1α null mice have already upregulated this parameter without training. Furthermore, untrained HIF-1α null mice have an increased capillary to fiber ratio and elevated oxidative enzyme activities. These changes correlate with constitutively activated AMP-activated protein kinase in the HIF-1α null muscles. Additionally, HIF-1α null muscles have decreased expression of pyruvate dehydrogenase kinase I, a HIF-1α target that inhibits oxidative metabolism. These data demonstrate that removal of HIF-1α causes an adaptive response in skeletal muscle akin to endurance training and provides evidence for the suppression of mitochondrial biogenesis by HIF-1α in normal tissue.


1997 ◽  
Vol 272 (6) ◽  
pp. H2541-H2546 ◽  
Author(s):  
G. Dornyei ◽  
G. Kaley ◽  
A. Koller

The role of endothelium in regulating venular resistance is not well characterized. Thus we aimed to elucidate the endothelium-derived factors involved in the mediation of responses of rat gracilis muscle venules to acetylcholine (ACh) and other vasoactive agents. Changes in diameter of perfusion pressure (7.5 mmHg)- and norepinephrine (10(-6) M)-constricted venules (approximately 225 microns in diam) to cumulative doses of ACh (10(-9) to 10(-4) M) and sodium nitroprusside (SNP, 10(-9) to 10(-4) M), before and after endothelium removal or application of various inhibitors, were measured. Lower doses of ACh elicited dilations (up to 42.1 +/- 4.7%), whereas higher doses of ACh resulted in smaller dilations or even constrictions. Endothelium removal abolished both ACh-induced dilation and constriction. In the presence of indomethacin (2.8 x 10(-5) M), a cyclooxygenase blocker, or SQ-29548 (10(-6) M), a thromboxane A2-prostaglandin H2 (PGH2) receptor antagonist, higher doses of ACh caused further dilation (up to 72.7 +/- 7%) instead of constriction. Similarly, lower doses of arachidonic acid (10(-9) to 10(-6) M) elicited dilations that were diminished at higher doses. These reduced responses were, however, reversed to substantial dilation by SQ-29548. The nitric oxide (NO) synthase blocker, N omega-nitro-L-arginine (L-NNA, 10(-4) M), significantly reduced the dilation to ACh (from 30.6 +/- 5.5 to 5.4 +/- 1.4% at 10(-6) M ACh). In contrast, L-NNA did not affect dilation to SNP. Thus ACh elicits the release of both NO and PGH2 from the venular endothelium.


2016 ◽  
Vol 121 (3) ◽  
pp. 699-708 ◽  
Author(s):  
Simone Porcelli ◽  
Mauro Marzorati ◽  
Lucia Morandi ◽  
Bruno Grassi

Aerobic training can be effective in patients with mitochondrial myopathies (MM) and McArdle's disease (McA). The aim of the study was to use noninvasive functional evaluation methods, specifically aimed at skeletal muscle oxidative metabolism, to evaluate the effects of an aerobic exercise training (cycle ergometer, 12 wk, 4 days/wk, ∼65-70% of maximal heart rate) in 6 MM and 7 McA. Oxygen uptake and skeletal muscle vastus lateralis fractional O2 extraction by near-infrared spectroscopy were assessed during incremental and low-intensity constant work rate (CWR) exercises before (BEFORE) and at the end (AFTER) of training. Peak O2 uptake increased significantly with training both in MM [14.7 ± 1.2 vs. 17.6 ± 1.4 ml·kg−1·min−1 (mean ± SD)] and in McA (18.5 ± 1.8 ml·kg−1·min−1 vs. 21.6 ± 1.9). Peak skeletal muscle fractional O2 extraction increased with training both in MM (22.0 ± 6.7 vs. 32.6 ± 5.9%) and in McA (18.5 ± 6.2 vs. 37.2 ± 7.2%). During low-intensity CWR in both MM and McA: V̇o2 kinetics became faster in AFTER, but only in the patients with slow V̇o2 kinetics in BEFORE; the transient overshoot in fractional O2 extraction kinetics disappeared. The level of habitual physical activity was not higher 3 mo after training (FOLLOW-UP vs. PRE). In MM and McA patients a home-based aerobic training program significantly attenuated the impairment of skeletal muscle oxidative metabolism and improved variables associated with exercise tolerance. Our findings indicate that in MM and McA patients near-infrared spectroscopy and V̇o2 kinetics can effectively detect the functional improvements obtained by training.


1989 ◽  
Vol 256 (3) ◽  
pp. R716-R721
Author(s):  
M. V. Westfall ◽  
M. M. Sayeed

This study examined whether alterations in cellular Ca2+ regulation contribute to previously observed changes in skeletal muscle sugar transport during bacteremia. Fasted male rats received saline (control) or bacteria (4 X 10(10) Escherichia coli/kg) intraperitoneally. Twelve hours later, basal and insulin-mediated 3-O-methylglucose (3MG) transport was measured in isolated soleus muscles. Measurements of 3MG transport in the presence of cytochalasin b or at a low temperature (0.5 degree C) indicated that altered sugar transport in bacteremic rat muscles was not due to nonspecific membrane permeability changes. To determine the role of Ca2+ in the pathogenesis of altered sugar transport during bacteremia, rats were treated with the Ca2+ antagonist diltiazem (DZ, 0.6-2.4 mg/kg) at various times (0, 0 + 7.5, 10 h) after saline or bacterial injection. In bacteremic rats given 2.4 mg/kg DZ at 10 h, basal and insulin-mediated transport were similar to control values. This dose of DZ had little effect on control muscles. The addition of 20 microM DZ to the incubation media did not affect basal or insulin-mediated 3MG transport in bacteremic rat muscles. Addition of the Ca2+ agonist BAY K 8644 to the incubation media had no effect on sugar transport in bacteremic rat muscles but caused alterations in control rat muscles that were comparable to those observed in bacteremia. These results suggest that alterations in Ca2+ regulation could contribute to the previously observed changes in sugar transport in skeletal muscles from bacteremic rats.


2007 ◽  
Vol 103 (3) ◽  
pp. 1093-1098 ◽  
Author(s):  
Bente Klarlund Pedersen ◽  
Thorbjörn C. A. Åkerström ◽  
Anders R. Nielsen ◽  
Christian P. Fischer

During the past 20 yr, it has been well documented that exercise has a profound effect on the immune system. With the discovery that exercise provokes an increase in a number of cytokines, a possible link between skeletal muscle contractile activity and immune changes was established. For most of the last century, researchers sought a link between muscle contraction and humoral changes in the form of an “exercise factor,” which could mediate some of the exercise-induced metabolic changes in other organs such as the liver and the adipose tissue. We suggest that cytokines and other peptides that are produced, expressed, and released by muscle fibers and exert either paracrine or endocrine effects should be classified as “myokines.” Since the discovery of interleukin (IL)-6 release from contracting skeletal muscle, evidence has accumulated that supports an effect of IL-6 on metabolism. We suggested that muscle-derived IL-6 fulfils the criteria of an exercise factor and that such classes of cytokines should be named “myokines.” Interestingly, recent research demonstrates that skeletal muscles can produce and express cytokines belonging to distinctly different families. Thus skeletal muscle has the capacity to express several myokines. To date the list includes IL-6, IL-8, and IL-15, and contractile activity plays a role in regulating the expression of these cytokines in skeletal muscle. The present review focuses on muscle-derived cytokines, their regulation by exercise, and their possible roles in metabolism and skeletal muscle function and it discusses which cytokines should be classified as true myokines.


1999 ◽  
Vol 86 (3) ◽  
pp. 909-914 ◽  
Author(s):  
Izumi Tabata ◽  
Youji Suzuki ◽  
Tetsuo Fukunaga ◽  
Toshiko Yokozeki ◽  
Hiroshi Akima ◽  
...  

This study assessed the effects of inactivity on GLUT-4 content of human skeletal muscle and evaluated resistance training as a countermeasure to inactivity-related changes in GLUT-4 content in skeletal muscle. Nine young men participated in the study. For 19 days, four control subjects remained in a −6° head-down tilt at all times throughout bed rest, except for showering every other day. Five training group subjects also remained at bed rest, except during resistance training once in the morning. The resistance training consisted of 30 isometric maximal voluntary contractions for 3 s each; leg-press exercise was used to recruit the extensor muscles of the ankle, knee, and hip. Pauses (3 s) were allowed between bouts of maximal contraction. Muscle biopsy samples were obtained from the lateral aspect of vastus lateralis (VL) muscle before and after the bed rest. GLUT-4 content in VL muscle of the control group was significantly decreased after bed rest (473 ± 48 vs. 398 ± 66 counts ⋅ min−1 ⋅ μg membrane protein−1, before and after bed rest, respectively), whereas GLUT-4 significantly increased in the training group with bed rest (510 ± 158 vs. 663 ± 189 counts ⋅ min−1 ⋅ μg membrane protein−1, before and after bed rest, respectively). The present study demonstrated that GLUT-4 in VL muscle decreased by ∼16% after 19 days of bed rest, and isometric resistance training during bed rest induced a 30% increase above the value of GLUT-4 before bed rest.


2016 ◽  
Vol 310 (2) ◽  
pp. R125-R133 ◽  
Author(s):  
Patrick C. Turnbull ◽  
Amanda B. Longo ◽  
Sofhia V. Ramos ◽  
Brian D. Roy ◽  
Wendy E. Ward ◽  
...  

Adipose triglyceride lipase (ATGL) catalyzes the rate-limiting removal of the first fatty acid from a triglyceride. ATGL is activated by comparative gene identification-58 and inhibited by G(0)/G(1) switch gene-2 protein (G0S2). Research in other tissues and cell culture indicates that inhibition is dependent on relative G0S2-to-ATGL protein content. G0S2 may also have several roles within mitochondria; however, this has yet to be observed in skeletal muscle. The purpose of this study was to determine if muscle G0S2 relative to ATGL content would decrease to facilitate intramuscular lipolysis following endurance training. Male Sprague-Dawley rats ( n = 10; age 51–53 days old) were progressively treadmill trained at a 10% incline for 8 wk ending with 25 m/min for 1 h compared with control. Sciatic nerve stimulation for hind-limb muscle contraction (and lipolysis) was administered for 30 min to one leg, leaving the opposing leg as a resting control. Soleus (SOL), red gastrocnemius (RG), and white gastrocnemius were excised from both legs following stimulation or control. ATGL protein increased in all trained muscles. Unexpectedly, G0S2 protein was greater in the trained SOL and RG. In RG-isolated mitochondria, G0S2 also increased with training, yet mitochondrial G0S2 content was unaltered with acute contraction; therefore, any role of G0S2 in the mitochondria does not appear to be acutely mediated by content alone. In summary, G0S2 increased with training in oxidative muscles and mitochondria but not following acute contraction, suggesting that inhibition is not through relative G0S2-to-ATGL content but through more complicated intracellular mechanisms.


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