Effect of Metabolic Changes on Force Generation in Skeletal Muscle During Maximal Exercise

Skeletal muscle injury is often assessed by clinical findings (history, pain, tenderness, strength loss), by imaging, or by invasive techniques. The purpose of this work was to determine if in vivo proton magnetic resonance spectroscopy (1H MRS) could reveal metabolic changes in murine skeletal muscle after contraction-induced injury. We compared findings in the tibialis anterior muscle from both healthy wild-type (WT) muscles (C57BL/10 mice) and dystrophic ( mdx mice) muscles (an animal model for human Duchenne muscular dystrophy) before and after contraction-induced injury. A mild in vivo eccentric injury protocol was used due to the high susceptibility of mdx muscles to injury. As expected, mdx mice sustained a greater loss of force (81%) after injury compared with WT (42%). In the uninjured muscles, choline (Cho) levels were 47% lower in the mdx muscles compared with WT muscles. In mdx mice, taurine levels decreased 17%, and Cho levels increased 25% in injured muscles compared with uninjured mdx muscles. Intramyocellular lipids and total muscle lipid levels increased significantly after injury but only in WT. The increase in lipid was confirmed using a permeable lipophilic fluorescence dye. In summary, loss of torque after injury was associated with alterations in muscle metabolite levels that may contribute to the overall injury response in mdx mice. These results show that it is possible to obtain meaningful in vivo 1H MRS regarding skeletal muscle injury.

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Skeletal muscle pyruvate dehydrogenase activity during maximal exercise in humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1995.269.3.e458 ◽

1995 ◽

Vol 269 (3) ◽

pp. E458-E468 ◽

Cited By ~ 29

Author(s):

C. T. Putman ◽

N. L. Jones ◽

L. C. Lands ◽

T. M. Bragg ◽

M. G. Hollidge-Horvat ◽

...

Keyword(s):

Skeletal Muscle ◽

Pyruvate Dehydrogenase ◽

Maximal Exercise ◽

Vastus Lateralis ◽

Active Form ◽

Lactate Production ◽

Glycolytic Flux ◽

Muscle Lactate ◽

Mitochondrial Oxidation ◽

Exercise In Humans

The regulation of the active form of pyruvate dehydrogenase (PDHa) and related metabolic events were examined in human skeletal muscle during repeated bouts of maximum exercise. Seven subjects completed three consecutive 30-s bouts of maximum isokinetic cycling, separated by 4 min of recovery. Biopsies of the vastus lateralis were taken before and immediately after each bout. PDHa increased from 0.45 +/- 0.15 to 2.96 +/- 0.38, 1.10 +/- 0.11 to 2.91 +/- 0.11, and 1.28 +/- 0.18 to 2.82 +/- 0.32 mmol.min-1.kg wet wt-1 during bouts 1, 2, and 3, respectively. Glycolytic flux was 13-fold greater than PDHa in bouts 1 and 2 and 4-fold greater during bout 3. This discrepancy between the rate of pyruvate production and oxidation resulted in substantial lactate accumulation to 89.5 +/- 11.6 in bout 1, 130.8 +/- 13.8 in bout 2, and 106.6 +/- 10.1 mmol/kg dry wt in bout 3. These events coincided with an increase in the mitochondrial oxidation state, as reflected by a fall in mitochondrial NADH/NAD, indicating that muscle lactate production during exercise was not an O2-dependent process in our subjects. During exercise the primary factor regulating PDHa transformation was probably intracellular Ca2+. In contrast, the primary regulatory factors causing greater PDHa during recovery were lower ATP/ADP and NADH/NAD and increased concentrations of pyruvate and H+. Greater PDHa during recovery facilitated continued oxidation of the lactate load between exercise bouts.

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Changes in shear wave propagation within skeletal muscle during active and passive force generation

Journal of Biomechanics ◽

10.1016/j.jbiomech.2019.07.019 ◽

2019 ◽

Vol 94 ◽

pp. 115-122 ◽

Cited By ~ 1

Author(s):

Allison B. Wang ◽

Eric J. Perreault ◽

Thomas J. Royston ◽

Sabrina S.M. Lee

Keyword(s):

Skeletal Muscle ◽

Wave Propagation ◽

Shear Wave ◽

Force Generation ◽

Passive Force

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Tilting of the light-chain region of myosin during step length changes and active force generation in skeletal muscle

Nature ◽

10.1038/375688a0 ◽

1995 ◽

Vol 375 (6533) ◽

pp. 688-691 ◽

Cited By ~ 144

Author(s):

Malcolm Irving ◽

Taylor St Claire Alien ◽

Cibele Sabido-David ◽

James S. Craik ◽

Birgit Brandmeier ◽

...

Keyword(s):

Skeletal Muscle ◽

Light Chain ◽

Step Length ◽

Force Generation ◽

Active Force ◽

Length Changes ◽

Active Force Generation

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Metabolic Changes in Single Human Muscle Fibres During Brief Maximal Exercise

Experimental Physiology ◽

10.1113/eph8602223 ◽

2001 ◽

Vol 86 (3) ◽

pp. 411-415 ◽

Cited By ~ 40

Author(s):

C. Karatzaferi ◽

A. de Haan ◽

W. van Mechelen ◽

A. J. Sargeant

Keyword(s):

Maximal Exercise ◽

Human Muscle ◽

Metabolic Changes ◽

Muscle Fibres

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Increased skeletal muscle phosphocreatine recovery after sub-maximal exercise is associated with increased carotid intima–media thickness

Atherosclerosis ◽

10.1016/j.atherosclerosis.2010.11.037 ◽

2011 ◽

Vol 215 (1) ◽

pp. 214-217 ◽

Cited By ~ 1

Author(s):

Hideo Makimura ◽

Takara L. Stanley ◽

Noelle Sun ◽

Jean M. Connelly ◽

Linda C. Hemphill ◽

...

Keyword(s):

Skeletal Muscle ◽

Maximal Exercise ◽

Intima Media Thickness ◽

Carotid Intima Media Thickness ◽

Media Thickness

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Cardiovascular effects of dobutamine during exercise in dogs

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1989.257.3.h954 ◽

1989 ◽

Vol 257 (3) ◽

pp. H954-H960

Author(s):

G. C. Haidet ◽

T. I. Musch ◽

D. B. Friedman ◽

G. A. Ordway

Keyword(s):

Skeletal Muscle ◽

Heart Rate ◽

Blood Flow ◽

Adrenergic Receptors ◽

Adrenergic Receptor ◽

Maximal Exercise ◽

Cardiovascular Effects ◽

Receptor Reserve ◽

Concomitant Reduction ◽

Stimulation Of

To test the hypothesis that stimulation of adrenergic receptors in the heart is maximal during maximal exercise, and to determine whether generalized stimulation of adrenergic receptors during strenuous exercise produces significant alterations in the normal regional distribution of blood flow that occurs during exercise, we evaluated the cardiovascular effects of the infusion of dobutamine (40 micrograms.kg-1.min-1) in mongrel dogs during treadmill running. During maximal exercise, the dobutamine infusion resulted in a significant (P less than 0.05) increase in heart rate. Exercise capacity, total body O2 consumption (VO2), and maximal arteriovenous O2 difference, however, each were reduced during the infusion of this drug. A concomitant reduction in maximal blood flow to locomotive skeletal muscle occurred. The infusion of dobutamine also resulted in an increase in heart rate at a strenuous level of submaximal exercise. However, unlike during maximal exercise, VO2 was unchanged. Blood flow to locomotive skeletal muscle increased, and there was a concomitant reduction in arteriovenous O2 difference. Blood flow reductions that normally occur in splanchnic circulations during strenuous and during maximal exercise were generally somewhat attenuated during the infusion of this drug. Thus, dobutamine, a sympathomimetic agent, produces significant cardiovascular effects when infused in high doses during exercise. Our results demonstrate that beta-adrenergic receptor reserve exists in the heart during maximal exercise in dogs. In addition, the peripheral responses that occur during the infusion of the drug provide additional evidence that different degrees of adrenergic receptor reserve normally appear to be present within different regional circulations during strenuous and during maximal exercise.

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Absence of myofibrillar creatine kinase and diaphragm isometric function during repetitive activation

Journal of Applied Physiology ◽

10.1152/jappl.1998.84.4.1166 ◽

1998 ◽

Vol 84 (4) ◽

pp. 1166-1173 ◽

Cited By ~ 14

Author(s):

John J. Labella ◽

Monica J. Daood ◽

A. P. Koretsky ◽

Brian B. Roman ◽

Gary C. Sieck ◽

...

Keyword(s):

Skeletal Muscle ◽

Creatine Kinase ◽

Muscle Function ◽

Isometric Force ◽

Force Generation ◽

Fatigue Properties ◽

Specific Force ◽

Null Mutant ◽

Isometric Muscle

Creatine kinase (CK) provides ATP buffering in skeletal muscle and is expressed as 1) cytosolic myofibrillar CK (M-CK) and 2) sarcomeric mitochondrial CK (ScCKmit) isoforms that differ in their subcellular localization. We compared the isometric contractile and fatigue properties of 1) control CK-sufficient (Ctl), 2) M-CK-deficient (M-CK[−/−]), and 3) combined M-CK/ScCKmit-deficient null mutant (CK[−/−]) diaphragm (Dia) to determine the effect of the absence of M-CK activity on Dia performance in vitro. Baseline contractile properties were comparable across groups except for specific force, which was ∼16% lower in CK[−/−] Dia compared with M-CK[−/−] and Ctl Dia. During repetitive activation (40 Hz, [Formula: see text] duty cycle), force declined in all three groups. This decline was significantly greater in CK[−/−] Dia compared with Ctl and M-CK[−/−] Dia. The pattern of force decline did not differ between M-CK[−/−] and Ctl Dia. We conclude that Dia isometric muscle function is not absolutely dependent on the presence of M-CK, whereas the complete absence of CK acutely impairs isometric force generation during repetitive activation.

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Estimation of capillary density in human skeletal muscle based on maximal oxygen consumption rates

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00559.2003 ◽

2003 ◽

Vol 285 (6) ◽

pp. H2382-H2391 ◽

Cited By ~ 27

Author(s):

B. J. McGuire ◽

T. W. Secomb

Keyword(s):

Skeletal Muscle ◽

Oxygen Consumption ◽

Oxygen Transport ◽

Human Skeletal Muscle ◽

Maximal Exercise ◽

Maximal Oxygen Consumption ◽

Capillary Density ◽

Transport Processes ◽

Whole Body ◽

Density Values

A previously developed Krogh-type theoretical model was used to estimate capillary density in human skeletal muscle based on published measurements of oxygen consumption, arterial partial pressure of oxygen, and blood flow during maximal exercise. The model assumes that oxygen consumption in maximal exercise is limited by the ability of capillaries to deliver oxygen to tissue and is therefore strongly dependent on capillary density, defined as the number of capillaries per unit cross-sectional area of muscle. Based on an analysis of oxygen transport processes occurring at the microvascular level, the model allows estimation of the minimum number of straight, evenly spaced capillaries required to achieve a given oxygen consumption rate. Estimated capillary density values were determined from measurements of maximal oxygen consumption during knee extensor exercise and during whole body cycling, and they range from 459 to 1,468 capillaries/mm2. Measured capillary densities, obtained with either histochemical staining techniques or electron microscopy on quadriceps muscle biopsies from healthy subjects, are generally lower, ranging from 123 to 515 capillaries/mm2. This discrepancy is partly accounted for by the fact that capillary density decreases with muscle contraction and muscle biopsy samples typically are strongly contracted. The results imply that estimates of maximal oxygen transport rates based on capillary density values obtained from biopsy samples do not fully reflect the oxygen transport capacity of the capillaries in skeletal muscle.

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