ArticlePDF AvailableLiterature Review

A Mechanistic Approach to Blood Flow Occlusion

November 2009
International Journal of Sports Medicine 31(1):1-4

DOI:10.1055/s-0029-1239499

Source
PubMed

Authors:

Gabriel J Wilson

University of Illinois Urbana-Champaign

Jacob M Wilson

Applied Science and Performance Institute

Low-Intensity occlusion training provides a unique beneficial training mode for promoting muscle hypertrophy. Training at intensities as low as 20% 1RM with moderate vascular occlusion results in muscle hypertrophy in as little as three weeks. The primary mechanisms by which occlusion training is thought to stimulate growth include, metabolic accumulation, which stimulates a subsequent increase in anabolic growth factors, fast-twitch fiber recruitment (FT), and increased protein synthesis through the mammalian target of rapamycin (mTOR) pathway. Heat shock proteins, Nitric oxide synthase-1 (NOS-1) and Myostatin have also been shown to be affected by an occlusion stimulus. In conclusion, low-intensity occlusion training appears to work through a variety of mechanisms. The research behind these mechanisms is incomplete thus far, and requires further examination, primarily to identify the actual metabolite responsible for the increase in GH with occlusion, and determine which mechanisms are associated to a greater degree with the hypertrophic/anti-catabolic changes seen with blood flow restriction.

Mechanisms by which blood occlusion training increases strength and muscular Hypertrophy. Arrows indicate stimulation, and blocked lines indicate inhibition. HSP = Heat shock proteins, GH = Growth Hormone, NO = Nitric oxide, IGF-1 = Insulin like growth factor, GHRH = Growth Hormone Releasing Hormone.

…

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Review 1

Loenneke JP et al. A Mechanistic Approach to Blood Flow … Int J Sports Med 2010; 31: 1 – 4

accepted after revision

August 17, 2009

Bibliography

DOI http://dx.doi.org/

10.1055/s-0029-1239499

Published online:

November 2, 2009

Int J Sports Med 2010; 31:

1 – 4 © Georg Thieme

Verlag KG Stuttgart · New York

ISSN 0172-4622

Correspondence

J. P. Loenneke

Southeast Missouri State

University Health, Human

Performance and Recreation

One University Plaza

63701 Cape Girardeau

United States

Tel.: 573-450-2952

Fax: 573-651-5150

jploenneke1s@semo.edu

Key words

● ▶ HSP 72

● ▶ growth hormone

● ▶ lactate

● ▶ mTOR

● ▶ hypertrophy

● ▶ myostatin

A Mechanistic Approach to Blood Flow Occlusion

rehabilitation, speciﬁ cally ACL injuries, cardiac

rehabilitation patients, the elderly [33, 36] and

even astronauts [12] . Although muscle hypertro-

phy would likely beneﬁ t those special populations,

more research should be done to further our

understanding of the proposed beneﬁ ts to each.

The primary mechanisms by which occlusion

training stimulates growth include: metabolic

accumulation which stimulates a subsequent

increase in anabolic growth factors, fast-twitch

ﬁ ber recruitment (FT), and increased protein

synthesis through the mammalian target of

rapamycin (mTOR) pathway. Increases in heat

shock proteins (HSP), Nitric oxide synthase-1

(NOS-1), and decreased expression of Myostatin

have also been observed [15] . The purpose of this

manuscript is to describe the physiologic mecha-

nisms by which vascular occlusion leads to skel-

etal muscle hypertrophy.

Metabolic Accumulation and Growth

Hormone

Whole blood lactate [8, 34] , plasma lactate

[7, 28, 33] and muscle cell lactate [14, 15] are all

increased in response to exercise with blood ﬂ ow

Introduction

The American College of Sports Medicine (ACSM)

recommends lifting a weight of at least 65 % of

one ’ s one repetition maximum (1RM) to achieve

muscular hypertrophy under normal conditions.

It is believed that anything below this intensity

rarely produces substantial muscle hypertrophy

or strength gains [17] . However, some individu-

als are unable to withstand the high mechanical

stress placed upon the joints during heavy resist-

ance training. Therefore, scientists have sought

lower intensity alternatives such as blood occlu-

sion training, also known as KAATSU training.

Blood occlusion training, as the name implies,

involves decreasing blood ﬂ ow to a muscle, by

application of a wrapping device, such as a blood

pressure cuﬀ . Evidence indicates that this style of

training can provide a unique, beneﬁ cial mode of

exercise in clinical settings, as it produces posi-

tive training adaptations at the equivalent to

physical activity of daily life (10 – 30 % of maximal

work capacity) [1] . Muscle hypertrophy has

recently been shown to occur during exercise as

low as 20 % of 1RM with moderate vascular occlu-

sion ( ~ 100 mmHg) [32] , which could be quite ben-

eﬁ cial to athletes [34] , patients in post operation

Authors J. P. Loenneke

1 , G. J. Wilson

2 , J. M. Wilson

Aﬃ liations 1 Southeast Missouri State University, Health, Human Performance, and Recreation, Cape Girardeau, United States

2 University of Illinois, Division of Nutritional Sciences, Champaign-Urbana, United States

3 Florida State University, Department of Nutrition, Food, and Exercise Science, Tallahassee, United States

Abstract

Low-Intensity occlusion training provides a

unique beneﬁ cial training mode for promoting

muscle hypertrophy. Training at intensities as

low as 20 % 1RM with moderate vascular occlu-

sion results in muscle hypertrophy in as little as

three weeks. The primary mechanisms by which

occlusion training is thought to stimulate growth

include, metabolic accumulation, which stimu-

lates a subsequent increase in anabolic growth

factors, fast-twitch ﬁ ber recruitment (FT), and

increased protein synthesis through the mam-

malian target of rapamycin (mTOR) pathway.

Heat shock proteins, Nitric oxide synthase-1

(NOS-1) and Myostatin have also been shown to

be aﬀ ected by an occlusion stimulus. In conclu-

sion, low-intensity occlusion training appears

to work through a variety of mechanisms. The

research behind these mechanisms is incomplete

thus far, and requires further examination, pri-

marily to identify the actual metabolite respon-

sible for the increase in GH with occlusion, and

determine which mechanisms are associated to a

greater degree with the hypertrophic / anti-cata-

bolic changes seen with blood ﬂ ow restriction.

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Loenneke JP et al. A Mechanistic Approach to Blood Flow … Int J Sports Med 2010; 31: 1 – 4

restriction. This is signiﬁ cant, as growth hormone (GH) has

shown to be stimulated by an acidic intramuscular environment

[34] . Evidence indicates that a low pH stimulates sympathetic

nerve activity through a chemoreceptive reﬂ ex mediated by

intramuscular metaboreceptors and group III and IV aﬀ erent ﬁ b-

ers [38] . Consequently, this same pathway has recently been

shown to play an important role in the regulation of hypophy-

seal secretion of GH [9, 38] .

However, changes in blood lactate are not always predictive of

changes in GH. To illustrate, Reeves et al. [28] showed that while

occlusion training resulted in a greater GH response than a non-

occluded control, there were no signiﬁ cant diﬀ erences in blood

lactate concentrations between groups. One possibility for the

disparity is that occluding blood ﬂ ow resulted in a slower diﬀ u-

sion of lactate out of muscle tissue, resulting in a more pro-

nounced intramuscular acidic environment and therefore, a

greater local stimulation of group IV aﬀ erents prior to its diﬀ u-

sion out of the cell. It is also possible that additional intramuscu-

lar metabolites stimulated changes in GH as group III and IV

aﬀ erents are sensitive to changes in adenosine, K + , H + , hypoxia,

and AMP. Increases in these metabolites during exercise is

thought to drive the pressor reﬂ ex leading to increased heart

rate and blood pressure, and it is postulated that this may also

facilitate increases in GH following occlusion training [27] .

Although there is no evidence that GH enhances muscle protein

synthesis when combined with traditional resistance exercise in

humans [40] , occlusion training may be diﬀ erent. Occlusion

training elevates GH to levels over that seen with traditional

resistance training [18, 19] . One study showed an increase in GH

~ 290 times greater than baseline measurements [34] . Research

on the eﬀ ects of supraphysiologic dosing of GH with traditional

resistance training in humans is limited. And while this research

has not yet demonstrated increased hypertrophy, it does appear

to indicate that GH administration elevates both the liver iso-

form of IGF-1 (Ea) in muscle as well as mechano-growth factor

[6] . More recently Ehrenborg and Rosen [6] have in an extensive

analysis of the literature on GH concluded that the majority of

the improvement with GH is due to the stimulation of collagen

synthesis which could provide a protective eﬀ ect in transferring

force from skeletal muscle externally and thus protect against

ruptures.

It is unclear if IGF-1 activity is increased in response to occlusion

training. More speciﬁ cally, Takano et al. [33] found a signiﬁ cant

increase, whereas two other studies found no increase [1, 15] .

Possible reasons as to why there was no increase could be related

to the low intensity of the exercise. Kawada and Ishii [15] postu-

late that IGF-1 may not be necessary for muscle hypertrophy

when other factors such as Myostatin, heat shock protein 72

(HSP-72), and nitric oxide synthase-1 (NOS-1) are changed in

favor of muscle growth.

Fiber Type Recruitment

The size principle suggests that under normal conditions slow

twitch ﬁ bers (ST) are recruited ﬁ rst and as the intensity increases,

fast twitch ﬁ bers (FT) are recruited as needed. The novel aspect

of occlusion training is that FT are recruited even though the

training intensity is low. Moritani et al. [25] postulated that

since the availability of oxygen is severely reduced during occlu-

sion, that a progressive recruitment of additional motor units

(MU) may take place to compensate for the deﬁ cit in force devel-

opment. Previous studies have shown signiﬁ cant increases in

MU ﬁ ring rate and MU spike amplitude associated with arterial

occlusion suggesting that the recruitment of high threshold MU

is not only aﬀ ected by the force and speed of contraction but also

the availability of oxygen [11, 13, 24] . Results from the use of

Integrated electromyography (iEMG) are consistent with these

ﬁ ndings, demonstrating no practical diﬀ erence in iEMG activity

between low intensity occlusion and high intensity non occlu-

sion training suggesting that a greater number of FT ﬁ bers are

activated at low intensities [34 – 36] .

mTOR Pathway

Increased rates of protein synthesis help to drive the skeletal

muscle hypertrophy response [39] . S6K1 phosphorylation – a

critical regulator of exercise-induced muscle protein synthesis

– has been demonstrated to increase with occlusion training.

Phosphorylation of S6K1 at Thr389 was increased by three-fold

immediately post exercise with occlusion training, and remained

elevated relative to control at three hours post exercise [7] .

Moreover research demonstrates that REDD1 (regulated in

development and DNA damage responses), which is normally

expressed in states of hypoxia, is not increased in response to

occlusion training even though hypoxia-inducible factor-1 alpha

(HIF-1 α ) is elevated. Normally HIF-1 α mRNA expression corre-

lates with a corresponding elevation in REDD1 [5] . The lack of

increases in REDD1 mRNA expression may prove to be impor-

tant as REDD1 works to reduce protein synthesis through inhibi-

tion of the mammalian target of rapamycin (mTOR), responsible

for the regulation of translation initiation [5] .

Currently there is no clear explanation for this paradox. How-

ever it is conceivable that an unknown factor is increased with

occlusion training, which inﬂ uences the transcription of HIF-1 α

and REDD1.

Heat Shock Proteins

HSPs are induced by stressors such as heat, ischemia, hypoxia,

free radicals, and act as chaperones to prevent misfolding or

aggregation of proteins. HSPs also appears useful to slowing

atrophy [15] , as HSP-72 plays a protective role in preventing pro-

tein degradation during periods of reduced contractile activity

[26] , by inhibiting key atrophy signaling pathways [4, 31] . The

primary pathway involved in mediating protein degradation is

the ubiquitin proteasome pathway. Recent in vivo data, demon-

strate that increased levels of HSP-70 is suﬃ cient to prevent

skeletal muscle disuse atrophy by inhibiting the promoter acti-

vation of atrogin-1 / muscle atrophy F-box (MAFbx) and muscle-

speciﬁ c RING ﬁ nger 1 (MuRF1) as well as the transcription

factors which regulate their expression, forkhead box O (Foxo)

and nuclear factor of P + NF-P + . Senf et al. [4] also observed that

Foxo3a, a member of the Foxo family upregulated during atro-

phy, not NF-P + is necessary for the increase in MAFbx and

MuRF1 promoter activities during disuse. Regardless both tran-

scriptional factor activities, Foxo and NF-P + are inhibited with

elevated HSP-70 levels. Incidentally, occlusion training has been

shown to increase HSP-72 in a rat model [15] , and Kawada and

Ishii [15] postulated that the increase in HSP-72 could be a

potential mechanism by which occlusion increases skeletal mus-

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Loenneke JP et al. A Mechanistic Approach to Blood Flow … Int J Sports Med 2010; 31: 1 – 4

cle hypertrophy and attenuates atrophy [36] , likely by inhibiting

the mediating pathways of the ubiquitin proteasome pathway.

NOS-1

Nitric oxide synthase is an enzyme responsible for converting

L-arginine into nitric oxide (NO), a small and electrically neutral

molecule capable of moving with ease through tissues [3] . Neu-

ronal NOS (nNOS) is found in the transmembrane / dystrophin

protein complex of skeletal muscle [29] . At rest, nNOS continu-

ally produces low levels of NO which appear to maintain satellite

cell quiescence. During exercise-induced contraction nNOS is

thought to be activated by mechanical shear forces, as well as

increased intracellular Ca

2 + concentrations [37] . nNOS is

increased in conjunction with occlusion training, possibly medi-

ated by the increased ﬂ ux of Ca

2 + , as well as reperfusion [15] .

According to Anderson et al., [2, 3] a spike in NO production trig-

gers the release of hepatocyte growth factor (HGF) from its bind-

ing to the muscle extracellular matrix followed by co-localization

with its c-MET receptor on satellite cells leading to their activa-

tion. This model is supported by a number of ﬁ ndings demon-

strating the inhibition of satellite cells in response to short-term

L-arginine methyl ester (L-NAME) treatment following injury or

mechanical stretch [3] .

Interestingly, Kawada and Ishii [15] did not show an increase in

NO, only nNOS, which could be due to the short life span of NO.

In this study, NO concentration was measured indirectly by its

oxidation products, therefore the obtained values might have

resulted from the production and breakdown of NO, both of

which might be inﬂ uenced by the occlusion of blood ﬂ ow.

Myostatin

Myostatin is a negative regulator of muscle growth and muta-

tions of this gene result in overgrowth of musculature in mice,

cattle, and humans [21, 22, 30] . Myostatin appears to inhibit sat-

ellite cell proliferation because Myostatin-null mice display

muscle hypertrophy and increased postnatal muscle growth,

which have been linked to increase satellite cell activity

[10, 20, 23] . McCroskery et al. [20] conclude that Myostatin is

expressed in adult satellite cells and that Myostatin regulates

satellite cell quiescence and self-renewal, showing it does play a

role in adult myogenesis.

Muscle Myostatin gene expression has been shown to decrease

as a result of mechanical overloading [16] , as well as in low

intensity exercise with occlusion [15] . Occlusion may cause

favorable hypertrophic changes in Myostatin as a result of

hypoxia and / or the accumulation of metabolic subproducts.

Conclusion

In conclusion low-intensity occlusion training works through a

variety of mechanisms, with the most prominent being meta-

bolic accumulation, ﬁ ber type activation, and mTOR signaling.

The research behind these mechanisms is incomplete thus far,

and more studies should be included to elucidate the actual

metabolite(s) responsible for the increase in GH with occlusion.

Furthermore, research should be directed towards determining

which particular mechanism(s) is associated to a greater degree

with the hypertrophic / anti-catabolic changes seen with blood

ﬂ ow restriction. While we have a base foundation of possibili-

ties, controlled studies addressing each proposed mechanism

Fig. 1 Mechanisms by which blood occlusion training increases strength and muscular Hypertrophy. Arrows indicate stimulation, and blocked lines

indicate inhibition. HSP = Heat shock proteins, GH = Growth Hormone, NO = Nitric oxide, IGF-1 = Insulin like growth factor, GHRH = Growth Hormone

Releasing Hormone.

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Loenneke JP et al. A Mechanistic Approach to Blood Flow … Int J Sports Med 2010; 31: 1 – 4

would provide a better understanding of each. For example, the

paradox of REDD1 and HIF-1 α should be examined to determine

if there is another factor that is increased in response to blood

ﬂ ow restriction. As postulated earlier, perhaps there is an

unknown factor that inﬂ uences the transcription of HIF-1 α and

REDD1 leading to the paradoxical increase in HIF-1 α with a

decrease in REDD1 expression. HSPs may also play an important

role, speciﬁ cally in attenuating skeletal muscle atrophy. While

animal studies show promise, human studies should be per-

formed to try and conﬁ rm the initial ﬁ ndings of Kawada and

Ishii.

The mechanisms described in this paper have all been shown to

potentially induce skeletal muscle hypertrophy in response to

blood-ﬂ ow restriction. Although some mechanisms may be

more prominent than others, all the mechanisms described

likely play at least some part in the enhanced skeletal muscle

hypertrophy response associated with occlusion training.

●

▶ Fig. 1 summarizes the mechanisms by which blood occlusion

training may stimulate muscular hypertrophy.

References

1 Abe T , Kearns C , Sato Y . Muscle size and strength are increased follow-

ing walk training with restricted venous blood ﬂ ow from the leg

muscle, Kaatsu-walk training . J Appl Physiol 2006 ; 100 : 1460 – 1466

2 Anderson JE . A role for nitric oxide in muscle repair: Nitric oxide-

mediated activation of muscle satellite cells . Mol Biol Cell 2000 ; 11 :

1859 – 1874

3 Anderson JE , Wozniak AC . Satellite cell activation on ﬁ bers: modeling

events in vivo – an invited review . Can J Physiol Pharmacol 2004 ; 82 :

300 – 310

4 Dodd S , Hain B , Judge A . Hsp70 prevents disuse muscle atrophy in

senescent rats . Biogerontology 2008

5 Drummond MJ , Fujita S , Takashi A , Dreyer HC , Volpi E , Rasmussen BB .

Human muscle gene expression following resistance exercise and

blood ﬂ ow restriction . Med Sci Sports Exerc 2008 ; 40 : 691 – 698

6 Ehrnborg C , Rosen T . Physiological and pharmacological basis for the

ergogenic eﬀ ects of growth hormone in elite sports . Asian J Androl

2008 ; 10 : 373 – 383

7 Fujita S , Abe T , Drummond MJ , Cadenas JG , Dreyer HC , Sato Y , Volpi E ,

Rasmussen BB . Blood ﬂ ow restriction during low-intensity resistance

exercise increases S6K1 phosphorylation and muscle protein synthe-

sis . J Appl Physiol 2007 ; 103 : 903 – 910

8 Gentil P , Oliveira E , Bottaro M . Time under tension and blood lactate

response during four diﬀ erent resistance training methods . J Physiol

Anthropol 2006 ; 25 : 339 – 344

9 Gosselink KL , Grindeland RE , Roy RR , Zhong H , Bigbee AJ , Grossman EJ ,

Edgerton VR . Skeletal muscle aﬀ erent regulation of bioassayable

growth hormone in the rat pituitary . J Appl Physiol 1998 ; 84 :

1425 – 1430

1 0 Grounds MD , Yablonka-Reuveni Z . Molecular and cell biology of skel-

etal muscle regeneration . Mol Cell Biol Hum Dis Ser 1993 ; 3 : 210 – 256

1 1 Idstrom JP , Subramanian VH , Chance B , Schersten T , Bylund-Fellenius

AC . Energy metabolism in relation to oxygen supply in contracting rat

skeletal muscle . Fed Proc 1986 ; 45 : 2937 – 2941

1 2 Iida H , Kurano M , Takano H , Kubota N , Morita T , Meguro K , Sato Y , Abe

T , Yamazaki Y , Uno K , Takenaka K , Hirose K , Nakajima T . Hemodynamic

and neurohumoral responses to the restriction of femoral blood ﬂ ow

by KAATSU in healthy subjects . Eur J Appl Physiol 2007 ; 100 : 275 –

285

1 3 Katz A , Sahlin K . E ﬀ ect of decreased oxygen availability on NADH and

lactate contents in human skeletal muscle during exercise . Acta Phys-

iol Scand 1987 ; 131 : 119 – 127

1 4 Kawada S , Ishii N . Changes in skeletal muscle size, ﬁ ber-type compo-

sition and capillary supply after chronic venous occlusion in rats . Acta

Physiol Scand 2007 ; 192 : 541 – 549

1 5 Kawada S , Ishii N . Skeletal muscle hypertrophy after chronic restric-

tion of venous blood ﬂ ow in rats . Med Sci Sports Exerc 2005 ; 37 :

1144 – 1150

1 6 Kawada S , Tach i C , Ishii N . Content and localization of myostatin in

mouse skeletal muscles during aging, mechanical unloading and

reloading . J Muscle Res Cell Motil 2001 ; 22 : 627 – 633

1 7 Kraemer WJ , Adams K , Cafarelli E , Dudley GA , Dooly C , Feigenbaum MS ,

Fleck SJ , Franklin B , Fry AC , Hoﬀ man JR , Newton RU , Potteiger J , Stone

MH , Ratamess NA , Triplett-McBride T . American College of Sports

Medicine position stand. Progression models in resistance training for

healthy adults . Med Sci Sports Exerc 2002 ; 34 : 364 – 380

1 8 Kraemer WJ , Gordon SE , Fleck SJ , Marchitelli LJ , Mello R , Dziados JE ,

Friedl K , Harman E , Maresh C , Fr y AC . Endogenous anabolic hormonal

and growth factor responses to heav y resistance exercise in males and

females . Int J Sports Med 1991 ; 12 : 228 – 235

1 9 Kraemer WJ , Marchitelli L , Gordon SE , Harman E , Dziados JE , Mello R ,

Frykman P , McCurry D , Fleck SJ . Hormonal and growth factor responses

to heavy resistance exercise protocols . J Appl Physiol 1990 ; 69 :

1442 – 1450

2 0 McCroskery S , Thomas M , Maxwell L , Sharma M , Kambadur R . M y o s t a -

tin negatively regulates satellite cell activation and self-renewal . J Cell

Biol 2003 ; 162 : 1135 – 1147

2 1 McPherron AC , Lawler AM , Lee SJ . Regulation of skeletal muscle mass

in mice by a new TGF-beta superfamily member . Nature 1997 ; 387 :

83 – 90

2 2 McPherron AC , Lee SJ . Double muscling in cattle due to mutations in

the myostatin gene . Proc Natl Acad Sci USA 1997 ; 94 : 12457 – 12461

2 3 Mesires NT , Doumit ME . Satellite cell proliferation and diﬀ erentiation

during postnatal growth of porcine skeletal muscle . Am J Physiol Cell

Physiol 2002 ; 282 : C899 – 906

2 4 Moritani T , Muro M , Nagata A . Intramuscular and surface electromyo-

gram changes during muscle fatigue . J Appl Physiol 1986 ; 60 :

1179 – 1185

2 5 Moritani T , Sherman WM , Shibata M , Matsumoto T , Shinohara M . O x y -

gen availability and motor unit activity in humans . Eur J Appl Physiol

1992 ; 64 : 552 – 556

2 6 Naito H , Powers SK , Demirel HA , Sugiura T , Dodd SL , Aoki J . H e a t s t r e s s

attenuates skeletal muscle atrophy in hindlimb-unweighted rats .

J Appl Physiol 2000 ; 88 : 359 – 363

2 7 Pierce JR , Clark BC , Ploutz-Snyder LL , Kanaley JA . Growth hormone and

muscle function responses to skeletal muscle ischemia . J Appl Physiol

2006 ; 101 : 1588 – 1595

2 8 Reeves GV , Kraemer RR , Hollander DB , Clavier J , Thomas C , Francois M ,

Castracane VD . Comparison of hormone responses following light

resistance exercise with partial vascular occlusion and moderately

diﬃ cult resistance exercise without occlusion . J Appl Physiol 2006 ;

101 : 1616 – 1622

2 9 Reid MB . Role of nitric oxide in skeletal muscle: synthesis, distribution

and functional importance . Acta Physiol Scand 1998 ; 162 : 401 – 409

3 0 Schuelke M , Wagner KR , Stolz LE , Hubner C , Riebel T , Komen W , Braun

T , Tobin JF , Lee SJ . Myostatin mutation associated with gross muscle

hypertrophy in a child . N Engl J Med 2004 ; 350 : 2682 – 2688

3 1 Senf SM , Dodd SL , McClung JM , Judge AR . Hsp70 overexpression inhib-

its NF-kappaB and Foxo3a transcriptional activities and prevents skel-

etal muscle atrophy . FASEB J 2008 ; 22 : 3836 – 3845

3 2 Sumide T , Sakuraba K , Sawaki K , Ohmura H , Tamura Y . E ﬀ ect of resist-

ance exercise training combined with relatively low vascular occlu-

sion . J Sci Med Sport 2007

3 3 Takano H , Morita T , Iida H , Asada K , Kato M , Uno K , Hirose K , Matsumoto

A , Takenaka K , Hirata Y , Eto F , Nagai R , Sato Y , Nakajima T . Hemody-

namic and hormonal responses to a short-term low-intensity resist-

ance exercise with the reduction of muscle blood ﬂ ow . Eur J Appl

Physiol 2005 ; 95 : 65 – 73

3 4 Takarada Y , Nakamura Y , Aruga S , Onda T , Miyazaki S , Ishii N . Rapid

increase in plasma growth hormone after low-intensity resistance

exercise with vascular occlusion . J Appl Physiol 2000 ; 88 : 6 1 – 6 5

3 5 Takarada Y , Ta ka za wa H , Sato Y , Takebayashi S , Tanaka Y , Ishii N . E ﬀ ects

of resistance exercise combined with moderate vascular occlusion on

muscular function in humans . J Appl Physiol 2000 ; 88 : 2097 – 2106

3 6 Takarada Y , Taka za wa H , Ishii N . Application of vascular occlusion

diminsh disuse atrophy of knee extensor muscles . Med Sci Sports

Exerc 2000 ; 32 : 2035 – 2039

3 7 Uematsu M , Ohara Y , Navas JP , Nishida K , Murphy TJ , Alexander RW ,

Nerem RM , Harrison DG . Regulation of endothelial cell nitric oxide

synthase mRNA expression by shear stress . Am J Physiol 1995 ; 269 :

C1371 – C1378

3 8 Victor RG , Seals DR . R e ﬂ ex stimulation of sympathetic outﬂ ow during

rhythmic exercise in humans . Am J Physiol 1989 ; 257 : H2017 – H2024

3 9 Wang X , Proud CG . The mTOR pathway in the control of protein syn-

thesis . Physiology (Bethesda) 2006 ; 21 : 362 – 369

4 0 Yarasheski KE , Campbell JA , Smith K , Rennie MJ , Holloszy JO , Bier DM .

E ﬀ ect of growth hormone and resistance exercise on muscle growth

in young men . Am J Physiol 1992 ; 262 : E261 – E267

Downloaded by: Dot. Lib Information. Copyrighted material.

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Jan 2025

Aerobic training with blood flow restriction (AT-BFR) has shown promise in enhancing both aerobic capacity and exercise performance. The aim of this review was to systematically analyze the evidence regarding the effectiveness of this novel training method on aerobic capacity, muscle strength, and hypertrophy in young adults. Studies were identified through a search of databases including PubMed, Scopus, Web of Science, SPORTDiscus, CINAHL, Cochrane Library, and EMBASE. A total of 16 studies, involving 270 subjects, were included in the meta-analysis. The results revealed that AT-BFR induced greater improvements in VO2max (SMD = 0.27, 95%CI: [0.02, 0.52], p < 0.05), and muscle strength (SMD = 0.39, 95%CI: [0.09, 0.69], p < 0.05), compared to aerobic training with no blood flow restriction (AT-noBFR). However, no significant effect was observed on muscle mass (SMD = 0.23, 95%CI: [-0.09, 0.56], p = 0.162). Furthermore, no moderating effects on the outcomes were found for individual characteristics or training factors. In conclusion, AT-BFR is more effective than AT-noBFR in improving aerobic capacity and muscle strength, making it a promising alternative to high-intensity training. Systematic Review Registration https://www.crd.york.ac.uk/prospero/, identifier CRD42024559872.

Acute Responses to Different Velocity-Loss Thresholds During Squat Training With and Without Blood-Flow Restriction

Article

Dec 2024
Int J Sports Physiol Perform

Purpose : To compare the acute effects on mechanical, metabolic, neuromuscular, and muscle contractile responses to different velocity-loss (VL) thresholds (20% and 40%) under distinct blood-flow conditions (free [FF] vs restricted [BFR]) in full squat (SQ). Methods : Twenty strength-trained men performed 4 SQ protocols with 60% 1-repetition maximum that differed in the VL within the set and in the blood-flow condition (FF20: FF with 20% VL; FF40: FF with 40% VL; BFR20: BFR with 20% VL; and BFR40: BFR with 40% VL). The level of BFR was 50% of the arterial occlusion pressure. Before and after the SQ protocols, the following tests were performed: (1) tensiomyography, (2) blood lactate, (3) countermovement jump, (4) maximal voluntary isometric SQ contraction, and (5) performance with the load that elicited a 1 m·s ⁻¹ at baseline measurements in SQ. Results : No “BFR × VL” interactions were observed. BFR protocols resulted in fewer repetitions and lower increases in lactate concentration than FF protocols. The 40% VL protocols completed more repetitions but resulted in lower mechanical performance and electromyography median frequency during the exercise than the 20% VL protocols. At postexercise, the 40% VL protocols also experienced greater blood lactate concentrations, higher alterations in tensiomyography-derived variables, and accentuated impairments in SQ and countermovement-jump performances. The 20% VL protocols showed an increased electromyography median frequency at postexercise maximal voluntary isometric contraction. Conclusions : Despite BFR-accelerated fatigue development during exercise, a given VL magnitude induced similar impairments in the distinct performance indicators assessed, regardless of the blood-flow condition.

Effects of blood flow restriction training in athletes: a systematic review meta-analysis

Article

Full-text available

Feb 2025
INT J SPORTS MED

This systematic review and meta-analysis evaluated the effects of blood flow restriction (BFR) training on strength and aerobic capacity in athletes, examining how training variables and participant characteristics influenced outcomes. Four databases were searched for peer-reviewed English-language studies, and the risk of bias and quality of evidence were assessed using RoB 2 and GRADEpro GDT. We evaluated pre- and post-test differences by a three-level meta-analysis using the meta and metafor packages. Subgroup analyses and both linear and nonlinear meta-regression methods were used to explore moderating factors. Sixteen studies with 'some concerns' risk of bias and low evidence level were included. Combining BFR with low-intensity resistance training produced an effect size (ES) of 0.25 for strength, while combining BFR with aerobic training had an ES of 0.42. For aerobic capacity, the ES of combining BFR with aerobic training was 0.58. Subgroup and regression analyses showed no significant differences. While BFR with low-intensity resistance training enhances strength, it does not result in additional gains. Adding BFR with aerobic training enhances both strength and aerobic capacity. Overall, BFR appears to offer the most benefits for male athletes in improving strength and aerobic capacity.

Acute Responses to Different Lifting Velocities During Squat Training With and Without Blood Flow Restriction

Article

Dec 2024
J STRENGTH COND RES

Cornejo-Daza, PJ, Sánchez-Valdepeñas, J, Páez-Maldonado, J, Rodiles-Guerrero, L, Sánchez-Moreno, M, Gómez-Guerrero, G, León-Prados, JA, and Pareja-Blanco, F. Acute responses to different lifting velocities during squat training with and without blood flow restriction. J Strength Cond Res XX(X): 000-000, 2024-The aims of the research were to compare the acute mechanical, metabolic, neuromuscular, and muscle mechanical responses to different lifting velocities (maximal vs. half-maximal) under distinct blood flow conditions (free [FF] vs. restricted [BFR]) in full-squat (SQ). Twenty resistance-trained males performed 4 protocols that differed in the velocity at which loads were lifted (MaxV: maximal velocity vs. HalfV: half-maximal velocity) and in the blood flow condition (FF: free-flow vs. BFR: 50% of arterial occlusion pressure). The relative intensity (60% 1 repetition maximum), volume (3 sets of 8 repetitions), and resting time (2 minutes) were matched between protocols. Mean propulsive force (MPF), mean propulsive velocity (MPV), mean propulsive power (MPP), and electromyography (EMG) values were recorded for each repetition. Tensiomyography (TMG), blood lactate, countermovement jump (CMJ), maximal voluntary isometric contraction in 90° SQ, and performance with the load that elicited a 1-m·s-1 velocity at baseline measurements (V1-load) in SQ were assessed at pre-exercise and postexercise. The MaxV protocols showed significantly greater MPF, MPV, MPP, and EMG amplitude during the exercise than the HalfV protocols (velocity effect, p < 0.05). The FF protocols achieved higher MPF and MPP during exercise than BFR (BFR effect, p < 0.05). The BFR protocols induced greater blood lactate after exercise (BFR × time interaction, p = 0.02), along with higher postexercise impairments in mechanical performance (BFR × time interaction, p < 0.05). The MaxV protocols elicited superior performance and greater muscle activation during exercise. The BFR protocols resulted in lower force and power production during exercise and exhibited higher performance impairments and increased metabolic stress postexercise.

Boys vs men differences in muscular fatigue, muscle and cerebral oxygenation during maximal effort isometric contractions: the effect of muscle blood flow restriction

Article

Full-text available

Nov 2024
EUR J APPL PHYSIOL

Purpose To examine whether the children’s superiority, over adults, to resist fatigue during repeated maximal-efforts depends on their often-cited oxidative advantage, attributed to greater muscle blood flow and O2-delivery. We also investigated the mechanisms underlying child–adult differences in muscle-oxygenation (due to O2-supply or O2-utilization) and examined if there are age-differences in cerebral-oxygenation response (a brain-activation index). Methods Eleven men (23.3 ± 1.8yrs) and eleven boys (11.6 ± 1.1 yrs) performed 15 maximal-effort handgrips (3-s contraction/3-s rest) under two conditions: free-flow circulation (FF) and arterial-occlusion (OCC). Force, muscle-oxygenation (TSImuscle) and cerebral-oxygenation (oxyhemoglobin-O2Hbcerebral; total hemoglobin-tHbcerebral; deoxyhemoglobin-HHbcerebral) were assessed. Results In boys, force declined less (− 26.3 ± 2.6 vs. − 34.4 ± 2.4%) and at slower rate (− 1.56 ± 0.16 vs. − 2.24 ± 0.17%·rep⁻¹) vs. men in FF (p < 0.01–0.05; d = 0.60–1.24). However, in OCC there were no age-differences in the magnitude (− 38.3 ± 3.0 vs. − 37.8 ± 3.0%) and rate (− 2.44 ± 0.26 vs. − 2.54 ± 0.26%·rep⁻¹) of force decline. Boys compared to men, exhibited less TSImuscle decline in both protocols, and lower muscle VO2 (p < 0.05). Boys, also, presented a smaller O2Hbcerebral and tHbcerebral rise than men in FF; exercising with OCC increased the O2Hbcerebral and tHbcerebral response in boys. Using MVIC as a covariate in FF condition, abolished boys-men differences in force and TSImuscle decline and O2Hbcerebral rise. Conclusion During repeated maximal-efforts: (i) blood flow is a significant contributor to children’s superiority over adults to resist fatigue; (ii) age-difference in muscle hypoxia/deoxygenation is rather attributed to men’s greater metabolic demand than to lower muscle-perfusion; and (iii) cerebral oxygenation/blood volume increase more in men than boys under free circulation, implying greater brain activation.

Die Effekte von „Medical Flossing“ auf das statische und dynamische Gleichgewicht bei Athlet*innen: Randomisierte kontrollierte experimentelle Studie

Article

Dec 2024

Sam Limpach

Zusammenfassung Die sportliche Leistung zu verbessern und die Häufigkeit an Verletzungen der unteren Extremitäten zu verringern, ist für Sportler*innen und ihr Betreuungspersonal von großer Bedeutung. Daher spielt die Gleichgewichtskontrolle, insbesondere die Sprunggelenk-Propriozeption, eine unbestreitbare Rolle. Medical Flossing könnte aufgrund ihrer theoretischen biomechanischen Mechanismen eine zeitweilige Verbesserung der Gleichgewichtskontrolle bewirken. Die Forschung zu möglichen Einflüssen von Flossing auf die Gleichgewichtskontrolle ist jedoch spärlich. In der vorliegenden Studie wurden die unmittelbaren Effekte von Flossing am Sprunggelenk in Kombination mit einer gewichtsbelastenden Bewegungsübung auf das statische und dynamische einbeinige Gleichgewicht untersucht. Vierzig gesunde Sportstudent*innen (Alter 22,12±3,04) wurden nach dem Zufallsprinzip einer Interventions- oder Kontrollgruppe zugeteilt. Beide Gruppen führten 3 Sätze von 10 erhöhten einbeinigen Wadenhebern durch. In der Interventionsgruppe wurde das Sprunggelenk während der Übung mit Flossing-Band umwickelt. Der Vor- und Nachtest bestand aus 4 Gleichgewichtsaufgaben mit unterschiedlichen Untergründen (stabil, instabil) und Bewegungen (statisch, dynamisch). Die wichtigste abhängige Variable war die Standardabweichung des „Center of Pressure“ in anterior-posteriorer und medio-lateraler Richtung, gemessen mit einer Kraftmessplatte. Die Ergebnisse zeigten keinen signifikanten Unterschied der Gleichgewichtskontrolle der beiden Gruppen bei den statischen Gleichgewichtsaufgaben. Allerdings führten beide Gruppen die dynamischen Aufgaben in der anterior-posterioren Richtung während des Post-Tests besser aus. Die medio-laterale Richtung der dynamischen Aufgaben führte zu einer signifikanten Abnahme (p=0,044) der Gleichgewichtskontrolle in der Interventionsgruppe in Bezug auf die Interaktion Untergrund*Gruppe. Die Ergebnisse dieser Studie deuten darauf hin, dass eine einmalige Flossing-Anwendung das einbeinige Gleichgewicht bei gesunden Sportstudent*innen nicht verbessert. Außerdem wurde eine Abnahme der Gleichgewichtskontrolle in medio-lateraler Richtung festgestellt.

Daily blood flow restriction does not affect muscle fiber capillarization and satellite cell content during two weeks of bed rest in healthy young men

Article

Dec 2024
J APPL PHYSIOL

The present study assessed whether single-leg daily blood flow restriction (BFR) treatment attenuates the decline in muscle fiber size, capillarization, and satellite cell (SC) content during 2 wk of bed rest in healthy, young men. Twelve healthy, young men (age: 24 ± 3 yr; BMI: 23.7 ± 3.1 kg/m2) were subjected to 2 wk of bed rest, during which one leg was exposed to three times daily 5 min of BFR, whereas the contralateral leg received sham treatment [control (CON)]. Muscle biopsies were obtained from the m. vastus lateralis from both the BFR and CON legs before and immediately after 2 wk of bed rest. Types I and II muscle fiber size, myonuclear content, capillarization, and SC content were assessed by immunohistochemistry. No significant decline in either type I or type II muscle fiber size was observed following bed rest, with no differences between the CON and BFR legs (P > 0.05). Type I muscle fiber capillary density increased in response to bed rest in both legs (P < 0.05), whereas other muscle fiber capillarization measures remained unaltered. SC content decreased in both type I (from 7.4 ± 3.2 to 5.9 ± 2.7 per 100 fibers) and type II (from 7.2 ± 3.4 to 6.5 ± 3.2 per 100 fibers) muscle fibers (main effect of time P = 0.018), with no significant differences between the BFR and CON legs (P > 0.05). In conclusion, 2 wk of bed rest has no effect on muscle capillarization and decreases the SC content, and daily BFR treatment does not affect skeletal muscle fiber size and SC content in healthy, young men.NEW & NOTEWORTHY We recently reported that the application of daily blood flow restriction (BFR) treatment does not preserve muscle mass or strength and does not modulate daily muscle protein synthesis rates during 2 wk of bed rest. Here, we show that 2 wk of bed rest resulted in a decrease in satellite cell (SC) content. In addition, the BFR treatment did not affect muscle fiber size, capillarization, and SC content during 2 wk of bed rest.

Joint Position Statement: progression models in resistance training for healthy adults

Article

Full-text available

Feb 2002

American College of Sports Medicine Position Stand on Progression Models in Resistance Training for Healthy Adults. Med. Sci. Sports Exerc. Vol. 34, No. 2, 2002, pp. 364-380. In order to stimulate further adaptation toward a specific training goal(s), progression in the type of resistance training protocol used is necessary. The optimal characteristics of strength-specific programs include the use of both concentric and eccentric muscle actions and the performance of both single- and multiple-joint exercises. It is also recommended that the strength program sequence exercises to optimize the quality of the exercise intensity (large before small muscle group exercises, multiple-joint exercises before single-joint exercises, and higher intensity before lower intensity exercises). For initial resistances, it is recommended that loads corresponding to 8-12 repetition maximum (RM) be used in novice training. For intermediate to advanced training, it is recommended that individuals use a wider loading range, from 1-12 RM in a periodized fashion, with eventual emphasis on heavy loading (1-6 RM) using at least 3-min rest periods between sets performed at a moderate contraction velocity (1-2 s concentric. 1-2 s eccentric). When training at a specific RM load, it is recommended that 2-10% increase in load be applied when the individual can perform the current workload for one to two repetitions over the desired number. The recommendation for training frequency is 2-3 d.wk(-1) for novice and intermediate training and 4-5 d.wk(-1) for advanced training. Similar program designs are recommended for hypertrophy training with respect to exercise selection and frequency. For loading, it is recommended that loads corresponding to 1-12 RM be used in periodized fashion, with emphasis on the 6-12 RM zone using 1- to 2-min rest periods between sets at a moderate velocity. Higher volume, multiple-set programs are recommended for maximizing hypertrophy. Progression in power training entails two general loading strategies: 1) strength training, and 2) use of light loads (30-60% of 1 RM) performed at a fast contraction velocity with 2-3 min of rest between sets for multiple sets per exercise. It is also recommended that emphasis be placed on multiple-joint exercises, especially those involving the total body. For local muscular endurance training, it is recommended that light to moderate loads (40-60% of 1 RM) be performed for high repetitions (> 15) using short rest periods (< 90 s). In the interpretation of this position stand, as with prior ones, the recommendations should be viewed in context of the individual's target goals, physical capacity, and training status.

Oxygen availability and motor unit activity in humans

Article

Full-text available

Nov 1992
Eur J Appl Physiol Occup Physiol

Six men were studied to determine the interrelationships among blood supply, motor unit (MU) activity and lactate concentrations during intermittent isometric contractions of the hand grip muscles. The subjects performed repeated contractions at 20% of maximal voluntary contraction (MVC) for 2 s followed by 2-s rest for 4 min with either unhindered blood circulation or arterial occlusion given between the 1st and 2nd min. The simultaneously recorded intramuscular MU spikes and surface electromyogram (EMG) data indicated that mean MU spike amplitude, firing frequency and the parameters of surface EMG power spectra (mean power frequency and root mean square amplitude) remained constant during the experiment with unhindered circulation, providing no electrophysiological signs of muscle fatigue. Significant increases in mean MU spike amplitude and frequency were, however, evident during the contractions with arterial occlusion. Similar patterns of significant changes in the surface EMG spectra parameters and venous lactate concentration were also observed, while the integrated force-time curves remained constant. These data would suggest that the metabolic state of the active muscles may have played an important role in the regulation of MU recruitment and rate coding patterns during exercise.

Hsp70 overexpression inhibits NF- B and Foxo3a transcriptional activities and prevents skeletal muscle atrophy

Article

Full-text available

Nov 2008
FASEB J

Heat shock protein 70 (Hsp70) is a highly conserved and ubiquitous protein that is reported to provide cytoprotection in various cell types and tissues. However, the importance of Hsp70 expression during skeletal muscle atrophy, when Hsp70 levels are significantly decreased, is not known. The current study aimed to determine whether plasmid-mediated overexpression of Hsp70, in the soleus muscle of rats, was sufficient to regulate specific atrophy signaling pathways and attenuate skeletal muscle disuse atrophy. We found that Hsp70 overexpression prevented disuse muscle fiber atrophy and inhibited the increased promoter activities of atrogin-1 and MuRF1. Importantly, the transcriptional activities of Foxo3a and NF-kappaB, which are implicated in the regulation of atrogin-1 and MuRF1, were abolished by Hsp70. These data suggest that Hsp70 may regulate key atrophy genes through inhibiting Foxo3a and NF-kappaB activities during disuse. Indeed, we show that specific inhibition of Foxo3a prevented the increases in both atrogin-1 and MuRF1 promoter activities during disuse. However, inhibition of NF-kappaB did not affect the activation of either promoter, suggesting its requirement for disuse atrophy is through its regulation of other atrophy genes. We conclude that overexpression of Hsp70 is sufficient to inhibit key atrophy signaling pathways and prevent skeletal muscle atrophy.

Endogenous Anabolic Hormonal and Growth Factor Responses to Heavy Resistance Exercise in Males and Females

Article

Full-text available

May 1991

To examine endogenous anabolic hormonal responses to two different types of heavy resistance exercise protocols (HREPs), eight male and eight female subjects performed two randomly assigned protocols (i.e. P-1 and P-2) on separate days. Each protocol consisted of eight identically ordered exercises carefully designed to control for load, rest period length, and total work (J) effects. P-1 utilized a 5 RM load, 3-min rest periods and had lower total work than P-2. P-2 utilized a 10 RM load, 1-min rest periods and had a higher total work than P-1. Whole blood lactate and serum glucose, human growth hormone (hGH), testosterone (T), and somatomedin-C [SM-C] (i.e. insulin-like growth factor 1, IGF-1) were determined pre-exercise, mid-exercise (i.e. after 4 of the 8 exercises), and at 0, 5, 15, 30, and 60 min post-exercise. Males demonstrated significant (p less than 0.05) increases above rest in serum T values, and all serum concentrations were greater than corresponding female values. Growth hormone increases in both males and females following the P-2 HREP were significantly greater at all time points than corresponding P-1 values. Females exhibited significantly higher pre-exercise hGH levels compared to males. The P-1 exercise protocol did not result in any hGH increases in females. SM-C demonstrated random significant increases above rest in both males and females in response to both HREPs.(ABSTRACT TRUNCATED AT 250 WORDS)

Skeletal muscle afferent regulation of bioassayable growth hormone in the rat pituitary

Article

Apr 1998

There are forms of growth hormone (GH) in the plasma and pituitary of the rat and in the plasma of humans that are undetected by presently available immunoassays (iGH) but can be measured by bioassay (bGH). Although the regulation of iGH release is well documented, the mechanism(s) of bGH release is unclear. On the basis of changes in bGH and iGH secretion in rats that had been exposed to microgravity conditions, we hypothesized that neural afferents play a role in regulating the release of these hormones. To examine whether bGH secretion can be modulated by afferent input from skeletal muscle, the proximal or distal ends of severed hindlimb fast muscle nerves were stimulated ( approximately 2 times threshold) in anesthetized rats. Plasma bGH increased approximately 250%, and pituitary bGH decreased approximately 60% after proximal nerve trunk stimulation. The bGH response was independent of muscle mass or whether the muscles were flexors or extensors. Distal nerve stimulation had little or no effect on plasma or pituitary bGH. Plasma iGH concentrations were unchanged after proximal nerve stimulation. Although there may be multiple regulatory mechanisms of bGH, the present results demonstrate that the activation of low-threshold afferents from fast skeletal muscles can play a regulatory role in the release of bGH, but not iGH, from the pituitary in anesthetized rats.

Effect of decreased oxygen availability on NADH and lactate contents in human skeletal muscle during exercise

Article

Sep 1987

Eight men cycled for 5 min at 120 +/- 6 W (mean +/- SE) at which O2 uptake was 50% of its maximal normoxic value, breathing room air (21% O2; normoxia) on one occasion and 11% O2 in N2 (respiratory hypoxia/hypoxic--Resp. Hx.) on the other. Biopsies were taken from the quadriceps femoris muscle. Oxygen uptake during exercise was not significantly different between Resp. Hx (1.59 +/- 0.08 1 min-1) and normoxia (1.55 +/- 0.08 1 min-1). At rest, muscle lactate was the same under both conditions but was four times higher after Resp. Hx (33.2 +/- 5.2 mmol kg-1 dry wt) than normoxic cycling (8.6 +/- 1.0 mmol kg-1 dry wt; P less than 0.01). The muscle lactate/pyruvate (which is proportional to cytosolic NADH/NAD) was significantly higher after Resp. Hx.(76 +/- 19) than after normoxic cycling (26 +/- 2; P less than 0.05). At rest, analytically determined NADH averaged 0.14 +/- 0.02 mmol kg-1 dry wt under both conditions. However, exercise during Resp. Hx. resulted in a significantly higher NADH content (0.17 +/- 0.01) than exercise during normoxia (0.12 +/- 0.01; P less than 0.01). Indirect evidence indicates that the difference in muscle NADH reflects a difference in the mitochondrial redox state (Sahlin & Katz 1986). The increased muscle NADH during Resp. Hx. therefore indicates a relative lack of O2 at the cellular level (muscle hypoxia). It is suggested that the increased lactate production during Resp. Hx. is a consequence of the cellular adaptation to muscle hypoxia (i.e. increases in cytosolic ADP, AMP, Pi and NADH).

Intramuscular and surface electromyogram changes during muscle fatigue

Article

May 1986

Twelve male subjects were tested to determine the effects of motor unit (MU) recruitment and firing frequency on the surface electromyogram (EMG) frequency power spectra during sustained maximal voluntary contraction (MVC) and 50% MVC of the biceps brachii muscle. Both the intramuscular MU spikes and surface EMG were recorded simultaneously and analyzed by means of a computer-aided intramuscular spike amplitude-frequency histogram and frequency power spectral analysis, respectively. Results indicated that both mean power frequency (MPF) and amplitude (rmsEMG) of the surface EMG fell significantly (P less than 0.001) together with a progressive reduction in MU spike amplitude and firing frequency during sustained MVC. During 50% MVC there was a significant decline in MPF (P less than 0.001), but this decline was accompanied by a significant increase in rmsEMG (P less than 0.001) and a progressive MU recruitment as evidenced by an increased number of MUs with relatively large spike amplitude. Our data suggest that the surface EMG amplitude could better represent the underlying MU activity during muscle fatigue and the frequency powers spectral shift may or may not reflect changes in MU recruitment and rate-coding patterns.

Energy metabolism in relation to oxygen supply in contracting rat skeletal muscle

Article

Jan 1987
Fed Proc

The regulation of the energy metabolism in contracting skeletal muscle is under close control, and several regulating factors have been reported. The aim of this study was to investigate the importance of the oxygen supply as a limiting factor for muscle performance during contractions and recovery from contractions. To perform well-controlled standardized experiments on contracting skeletal muscle, the perfused rat hind limb model was developed. The 31P NMR technique was adapted to the rat hind limb model. This enabled continuous nondestructive monitoring of the energy state at various levels of muscular activity. Significant correlations were found between oxygen delivery and oxygen consumption, lactate release, and glucose uptake, respectively. An increased degree of fatigue was observed at lower oxygen deliveries. In both soleus and gastrocnemius muscles, oxygen delivery correlated with the intramuscular concentrations of phosphocreatine (PCr), lactate, and glycogen. The 31P NMR experiments showed a correlation between oxygen delivery and the steady-state level of PCr/inorganic phosphate (Pi) during the contraction period. The rate of recovery in PCr/Pi after the contraction was also dependent on oxygen delivery. The results demonstrate a causal relationship between oxygen supply and energy state in contracting as well as recovering skeletal muscles.

Regulation of endothelial cell nitric oxide synthase mRNA expression by shear stress

Article

Jan 1996
Am J Physiol

Shear stress enhances expression of Ca(2+)-calmodulin-sensitive endothelial cell nitric oxide synthase (ecNOS) mRNA and protein in bovine aortic endothelial cells (BAEC). The present studies were performed to investigate mechanisms responsible for regulation of ecNOS mRNA expression by shear stress and to determine if this induction of ecNOS mRNA is accompanied by an enhanced nitric oxide (NO) production. Shear stresses of 15 dyn/cm2 for 3-24 h resulted in a two- to threefold increase of ecNOS mRNA content quantified by Northern analysis in BAEC. Shear stresses (1.2-15 dyn/cm2) for 3 h resulted in an induction of ecNOS mRNA in a dose-dependent manner. In human aortic endothelial cells, shear stresses of 15 dyn/cm2 for 3 h also resulted in ecNOS mRNA induction. In BAEC, this induction in ecNOS mRNA was prevented by coincubation with actinomycin D (10 micrograms/ml). The K+ channel antagonist tetraethylammonium chloride (3 mM) prevented increase in ecNOS mRNA in response to shear stress. The ecNOS promotor contains putative binding domains for AP-1 complexes, potentially responsive to activation of protein kinase C (PKC). However, selective PKC inhibitor calphostin C (100 nM) did not inhibit ecNOS induction by shear stress. Finally, production of nitrogen oxides under both basal conditions and in response to the calcium ionophore A-23187 (1 microM) by BAEC exposed to shear stress was increased approximately twofold compared with cells not exposed to shear stress. These data suggest that ecNOS mRNA expression is regulated by K+ channel opening, but not by activation of PKC, and that shear not only enhances ecNOS mRNA expression but increases capacity of endothelial cells to release NO.

Regulation of Skeletal Muscle Mass in Mice by a New TGF-?? Superfamily Member

Article

Jun 1997

The transforming growth factor-beta (TGF-beta) superfamily encompasses a large group of growth and differentiation factors playing important roles in regulating embryonic development and in maintaining tissue homeostasis in adult animals. Using degenerate polymerase chain reaction, we have identified a new murine TGF-beta family member, growth/differentiation factor-8 (GDF-8), which is expressed specifically in developing and adult skeletal muscle. During early stages of embryogenesis, GDF-8 expression is restricted to the myotome compartment of developing somites. At later stages and in adult animals, GDF-8 is expressed in many different muscles throughout the body. To determine the biological function of GDF-8, we disrupted the GDF-8 gene by gene targeting in mice. GDF-8 null animals are significantly larger than wild-type animals and show a large and widespread increase in skeletal muscle mass. Individual muscles of mutant animals weigh 2-3 times more than those of wild-type animals, and the increase in mass appears to result from a combination of muscle cell hyperplasia and hypertrophy. These results suggest that GDF-8 functions specifically as a negative regulator of skeletal muscle growth.