ORIGINAL RESEARCH
published: 17 Augus 2016
doi: 10.3389/ phys.2016.00333
F on ie s in Physiology | www. on ie sin.o g 1Augus 2016 | Volume 7 | A icle 333
Edi ed by:
G egoi e P. Mille ,
Uni e si y o Lausanne, Swi ze land
Re iewed by:
Tadej Debe ec,
Jože S e an Ins i u e, Slo enia
Thomas Rupp,
Uni e si y o Sa oy, F ance
*Co espondence:
José A. L. Calbe
[email p o ec ed]
Special y sec ion:
This a icle was submi ed o
Exe cise Physiology,
a sec ion o he jou nal
F on ie s in Physiology
Recei ed: 17 Ma ch 2016
Accep ed: 20 July 2016
Published: 17 Augus 2016
Ci a ion:
To es-Pe al a R, Losa-Reyna J,
Mo ales-Alamo D, González-Izal M,
Pé ez-Suá ez I, Ponce-González JG,
Izquie do M and Calbe JAL (2016)
Inc eased PIO2a Exhaus ion in
Hypoxia Enhances Muscle Ac i a ion
and Swi ly Relie es Fa igue: A
Placebo o a PIO2Dependen E ec ?
F on . Physiol. 7:333.
doi: 10.3389/ phys.2016.00333
Inc eased PIO2a Exhaus ion in
Hypoxia Enhances Muscle Ac i a ion
and Swi ly Relie es Fa igue: A
Placebo o a PIO2Dependen E ec ?
Ra ael To es-Pe al a1, 2, José Losa-Reyna1, 2, Da id Mo ales-Alamo1, 2,
Mi iam González-Izal3, Ismael Pé ez-Suá ez1, 2, Jesús G. Ponce-González1,
Mikel Izquie do3and José A. L. Calbe 1, 2*
1Depa men o Physical Educa ion, Uni e si y o Las Palmas de G an Cana ia, Las Palmas, Spain, 2Resea ch Ins i u e o
Biomedical and Heal h Sciences, Ins i u o Uni e si a io de In es igaciones Biomédicas y Sani a ias, Las Palmas, Spain,
3Depa men o Heal h Sciences, Public Uni e si y o Na a a, Tudela, Spain
To de e mine he le el o hypoxia om which muscle ac i a ion (MA) is educed du ing
inc emen al exe cise o exhaus ion (IE), and he ole played by PIO2in his p ocess, en
olun ee s (21 ±2 yea s) pe o med ou IE in se e e acu e hypoxia (SAH) (PIO2=73
mmHg). Upon exhaus ion, subjec s we e asked o con inue exe cising while he b ea hing
gas mix u e was swi ly changed o a placebo (73 mmHg) o o a highe PIO2(82, 92, 99,
and 142 mmHg), and he IE con inued un il a new exhaus ion. A he second exhaus ion,
he b ea hing gas was changed o oom ai (no moxia) and he IE con inued un il he inal
exhaus ion. MA, as e lec ed by he as us medialis (VM) and la e alis (VL) EMG aw
and no malized oo mean squa e (RMS aw, and RMSNz, espec i ely), no malized o al
ac i a ion index (TAINz), and bu s du a ion we e 8–20% lowe a exhaus ion in SAH
han in no moxia (P<0.05). The swi ch o a placebo o highe PIO2allowed o he
con inua ion o exe cise in all ins ances. RMS aw, RMSNz, and TAINz we e inc eased
by 5–11% when he PIO2was aised om 73 o 92, o 99 mmHg, and VL and VM
a e aged RMS aw by 7% when he PIO2was ele a ed om 73 o 142 mmHg (P<0.05).
The inc ease o VM-VL a e age RMS aw was linea ly ela ed o he inc ease in PIO2,
du ing he ansi ion om SAH o highe PIO2(R2=0.915, P<0.05). In conclusion,
inc eased PIO2a exhaus ion educes a igue and allows o he con inua ion o exe cise
in mode a e and SAH, ega dless o he e ec s o PIO2on MA. A ask ailu e, MA is
inc eased du ing he i s 10 s o inc eased PIO2when he IE is pe o med a a PIO2close
o 73 mmHg and he PIO2is inc eased o 92 mmHg o highe . O e all, hese indings
indica e ha one o he cen al mechanisms by which se e e hypoxia may cause cen al
a igue and ask ailu e is by educing he capaci y o eaching he app op ia e le el o
MA o sus ain he ask. The ac ha a exhaus ion in se e e hypoxia he exe cise was
con inued wi h he placebo-gas mix u e demons a es ha his cen al mechanism has
a cogni i e componen .
Keywo ds: a igue, pe o mance, hypoxia, al i ude, muscle ac i a ion, human expe imen a ion, exe cise,
oxygena ion
To es-Pe al a e al. Oxygena ion E ec s on Muscle Ac i a ion a Fa igue
INTRODUCTION
Muscle ac i a ion, as e lec ed by he oo mean squa e o he
elec omyog aphic signal (EMGRMS), is highe in se e e acu e
hypoxia (SAH) han no moxia a he same absolu e in ensi y, bu
lowe in hypoxia han in no moxia a he same ela i e in ensi y
(To es-Pe al a e al., 2014). Close o exhaus ion, he su ace
in eg a ed elec omyog aphic (iEMG) ac i i y is highe du ing
cons an -in ensi y exe cise in hype oxia (FIO2=0.30) han in
SAH (FIO2=0.10) (Amann e al., 2007). This could mean ha
hypoxia limi s he mo o d i e ou pu om he cen al ne ous
sys em (CNS) leading o educed muscle ac i a ion (MA) and
ask ailu e. In ag eemen wi h his idea, du ing exe cise in se e e
hypoxia, a igue is apidly elie ed by oxygena ion wi h no moxic
(Calbe e al., 2003a) o hype oxic gas (Amann e al., 2007).
I hypoxia dep esses muscle ac i a ion, oxygena ion should be
accompanied by an immedia e inc ease in MA while he in ensi y
o exe cise emains a he same absolu e le el. Howe e , i
emains unknown whe he he e gogenic e ec o an inc ease
in oxygena ion equi es a concomi an ele a ion o muscle
ac i a ion.
Du ing exe cise in se e e acu e (Calbe e al., 2003a, 2015a;
Amann e al., 2007; Mo ales-Alamo e al., 2015) and ch onic
hypoxia (Kayse e al., 1994; Calbe e al., 2003b) ask ailu e
is hough o be p edominan ly caused by cen al mechanisms
sensi i e o educed O2deli e y o he b ain (Goodall e al.,
2012, 2014) and o educed in e s i ial b ain PO2(Amann and
Calbe , 2008). A undamen al di e ence be ween exe cise in
se e e and mode a e hypoxia is he egion o he hemoglobin
oxygen dissocia ion cu e (ODC) a which he gas exchange
occu s in he lungs. In se e e hypoxia, pulmona y gas exchange
occu s in he s aigh egion o he ODC, implying ha a
small inc ease in a e ial oxygen p essu e (PaO2) would esul
in a g ea e ele a ion o a e ial hemoglobin sa u a ion (SaO2)
(Calbe e al., 2003a; Calbe and Lundby, 2009). In mode a e
hypoxia, pulmona y gas exchange occu s a he uppe and
la e egion o he ODC, whe e an imp o emen in PaO2
ansla es in o a smalle ele a ion o SaO2(Amann e al., 2007).
The ac ha inc easing inspi a o y oxygen p essu e (PIO2) o
hype oxic le els only elie ed a igue when applied a exhaus ion
in se e e hypoxia could indica e ha a subs an ial ele a ion o
a e ial oxygen con en (CaO2) is equi ed (Amann e al., 2007).
Howe e , he obse a ion by Amann e al. (2007) ha inc eased
PIO2does no elie e a igue du ing mode a e hypoxia could
indica e ha he inc ease in SaO2is e en mo e c i ical han he
ele a ion o PaO2, since in he la e egion o he ODC he
imp o emen o SaO2 o a gi en inc ease o PaO2is smalle . I
emains unknown wha le els o imp o emen in PaO2and CaO2
a e equi ed o elie e a igue and enhance he neu al ac i a ion
o muscles upon exhaus ion in hypoxia.
The e o e, he aims o his s udy we e o (a) de e mine he
in luence o he le el o hypoxia on a po en ial educ ion o
MA a exhaus ion; (b) de e mine he minimum inc ease in PIO2
needed o enhance muscle ac i a ion a exhaus ion in hypoxia;
and (c) ind ou i he e gogenic e ec o inc easing PIO2is always
accompanied by enhanced muscle ac i a ion, which would be an
indica ion o a p edominan ly cen al mechanism.
We hypo hesized ha an inc ease o PIO2upon exhaus ion
would apidly inc ease MA depending on he le el o hypoxia a
exhaus ion and he inspi a o y O2p essu e o he b ea hing gas.
MATERIALS AND METHODS
Subjec s
Ten heal hy men (age: 21.1 ±2.1 yea s, heigh : 173 ±8 cm,
body mass: 71 ±9 kg, body a : 16.6 ±4.5%, VO2max: 50.4 ±
4.7 mL.kg−1.min−1) ag eed o pa icipa e in his in es iga ion.
A e being in o med abou he expe imen s and he possible
isks associa ed wi h pa icipa ion hey p o ided w i en consen .
The s udy was pe o med by he Helsinki Decla a ion and was
app o ed by he E hical Commi ee o he Uni e si y o Las
Palmas de G an Cana ia (CEIH-2010-01 and CEIH-2009-01).
Gene al O e iew
This s udy was a pa o a la ge p ojec ha included
se e al expe imen s designed o add ess he mechanisms
limi ing whole body exe cise pe o mance in humans. The
esul s ocusing on muscle me abolism and O2 anspo ha e
been published (Calbe e al., 2015a; Mo ales-Alamo e al.,
2015). Body composi ion was de e mined by dual-ene gy x-
ay abso p iome y (DEXA) (Hologic QDR-1500, Hologic Co p.,
so wa e e sion 7.10, Wal ham, MA), du ing he amilia iza ion
sessions. The leg muscle mass was calcula ed om he DEXA
scans using he model o Wang e al. (1999). Subjec s epo ed
o he labo a o y o amilia ize wi h maximal exe cise es s
in no moxia and no moba ic hypoxia (Al i aine 200, SMTEC,
Swi ze land) on sepa a e days. Fo expe imen al pu poses,
subjec s pe o med wo se s o IE es s, he e called in asi e
and decep ion es . On he i s expe imen al day, all subjec s
pe o med he in asi e es s as p e iously desc ibed (Calbe
e al., 2015a) and on he second and hi d day, hey comple ed
he decep ion p o ocol. The exe cise es s we e ca ied ou on
a cycle e gome e (Lode Excalibu Spo 925900, G oningen,
The Ne he lands) and subjec s we e ins uc ed o pedal a 80
e olu ions pe minu e ( pm). To acili a e he main enance o
he a ge ed pedaling cadence, subjec s ecei ed isual eedback,
and e bal ins uc ions when de ia ions o 5 o mo e pm
occu ed.
Exe cise P o ocol
In asi e Expe imen s
Subjec s epo ed o he labo a o y a 07.00 a e an o e nigh
as om 22.00 h. A e ca he e iza ion (see below), subjec s we e
assigned o ei he an IE es o exhaus ion in no moxia (30 W/2
min) o hypoxia (PIO2=73 mmHg; 20 W/2 min; Al i aine 200,
SMTEC, Swi ze land), in andom o de and sepa a ed by 90
min es . Be o e he s a o he IE in hypoxia, subjec s we e
b ea hing he hypoxic gas o 3 min while hey we e pedaling
20–40 pm wi h he e gome e unloaded. A exhaus ion (Exh1),
he subjec s we e apidly swi ched o b ea h oom ai (no moxia)
and eques ed o con inue he exe cise a he same load o 2 min,
hen he load was inc eased by 20 W e e y 2 min un il exhaus ion
(Exh2). This was ollowed by a lunch b eak (a sandwich and
200 mL o apple o pineapple juice) and a 120 min es ing
F on ie s in Physiology | www. on ie sin.o g 2Augus 2016 | Volume 7 | A icle 333
To es-Pe al a e al. Oxygena ion E ec s on Muscle Ac i a ion a Fa igue
pe iod. The ea e , he IE in hypoxia was epea ed. A Exh1 he
subjec s we e eques ed o keep pedaling while a al e de ia ed
he inspi ed low o a 30 L anes hesia bag p e- illed wi h hypoxic
gas (FIO2= ∼13.3, PIO2= ∼91 mmHg) and a small amoun
o CO (7 mL·kg−1body mass). The gas was b ea hed in an open
ci cui sys em in a well- en ila ed oom un il he bag was almos
emp ied. The al e was hen e u ned o he p e ious posi ion
such ha he subjec s con inued he inc emen al es a his le el
o hypoxia (FIO2:∼13.3, PIO2:∼91 mmHg). A e 2 min a
he load elici ing exhaus ion, he in ensi y was inc eased by 20
W/2 min un il a new exhaus ion (Exh2). Again, subjec s we e
eques ed o keep pedaling while hey we e swi ched o b ea h
oom ai (no moxia). A e 2 min, he load was inc eased by 20
W/2 min un il exhaus ion (Exh3). The in asi e expe imen s we e
used o s udy he in luence o di e en le els o oxygena ion on
he hemodynamic esponses and a igue mechanisms in hypoxia,
as epo ed p e iously (Calbe e al., 2015a).
Decep ion P o ocol (Nonin asi e)
Subjec s pe o med ou IE es s on 2 di e en days, sepa a ed
by a leas 1 week. A 90 min eco e y pe iod was es ablished
be ween he wo es s ca ied ou on he same day (Figu e 1),
as p e iously done (Calbe e al., 2003a). This es ing pe iod is
su icien o allow o a ull eco e y o peak powe ou pu and
VO2max, as p e iously epo ed (Scha hag-Rosenbe ge e al.,
2014; Calbe e al., 2015a). Each decep ion es was composed o
an ini ial phase in se e e hypoxia (PIO2=73 mmHg) (HYP1),
ollowed by a second phase wi h a simila o a less se e e
le el o hypoxia (HYP2), which con inued wi h a inal phase in
no moxia (NX3). HYP1 s a ed wi h an in ensi y o 60 o 70
W which, a e 2 min was inc eased by 20 o 30 W e e y 2
min un il exhaus ion (Exh1). The 70 W s a ing load and he
s eps o 30 W we e used in one o he subjec s who was a well-
ained ia hle e, so he du a ion o his es was simila o he
du a ion o he es s pe o med by he o he subjec s. Like du ing
he in asi e expe imen s, be o e he s a o he IE in hypoxia,
subjec s we e b ea hing he hypoxic gas o 3 min while hey
we e pedaling a 20–40 pm wi h he e gome e unloaded. A
Exh1, he inspi ed gas mix u e was apidly changed o one o
ou di e en gas mix u es [PIO2=73 (placebo), 82, 92, and
99 mmHg, equi alen o 5200, 4400, 3600, and 3100 m abo e
sea le el, espec i ely]. Subjec s we e old and belie ed ha hey
we e ge ing no moxic gas a exhaus ion. These gas mix u es we e
adminis e ed in andom o de and wi h a double-blind design.
A e 2 min a he load elici ing Exh1, he load was inc eased
by 20 o 30 W e e y 2 min un il exhaus ion (Exh2). A Exh2,
he gas mix u e was apidly changed o oom ai (PIO2=142
mmHg) while he subjec s we e s ongly encou aged o con inue
pedaling. A e 2 min a he load elici ing Exh2, he load was
inc eased by 20 o 30 W e e y 2 min un il exhaus ion (Exh3).
Al hough he change o PIO2upon exhaus ion was in ended o
be main ained o 2 min be o e inc easing he load, in some
ins ances, o example du ing he placebo expe imen s, subjec s
a igued be o e eaching 2 min in he new oxygena ion condi ion.
In hese cases, he b ea hing gas mix u e was apidly changed o
no moxia, main ained o 2 min in no moxia, and hen inc eased
by 20 o 30 W e e y 2 min un il exhaus ion. Exhaus ion du ing
he IE es s was de ined by ei he he subjec s opping pedaling
o d opping pedaling a e below 60 pm du ing 5 s (o ea lie
i he cadence was d opping e y as ), despi e s ong e bal
encou agemen . A 30 L anes hesia bag was p e illed wi h he
a ge FIO2and used as a bu e in he ansi ion o HYP2, o
gain ew seconds o adjus he Al i aine in such a way ha
he a ge FIO2was ins an aneously adminis e ed a he s a
o he ansi ion. Du ing he i s 10–12 s o he ansi ions he
subjec s b ea hed om he anes hesia bag, hen a ou -way al e
was used o di ec he inspi a o y po o ei he he Al i aine
o oom ai . These 10 s (bag b ea hing) we e used o s abilize
he Al i aine a he a ge FIO2co esponding o each HYP2
phase.
FIGURE 1 | Expe imen al p o ocol. Each expe imen al day he subjec s pe o med wo inc emen al exe cise es s in andom o de . The inc emen al exe cise es
always began in se e e hypoxia (PIO2=73 mmHg). A exhaus ion (Exh1) he b ea hing gas mix u e was swi ly changed o ano he one wi h a g ea e oxygen PO2,
excep in one ins ance ha he gas adminis e ed was he same one he subjec s we e b ea hing in se e e acu e hypoxia, i.e., PIO2=73 mmHg, o c ea e a placebo
condi ion. Subjec s we e asked o con inue he exe cise and a e 2 min a he load elici ing Exh1, he load was inc eased by 20 o 30 W/2 min un il exhaus ion (Exh2).
Once again, subjec s we e asked o keep pedaling while he gas mix u e was swi ly changed o no moxia. A e 2 min a he load elici ing Exh2, he in ensi y was
inc eased by 20 o 30 W/2 min un il he inal exhaus ion (Exh 3). Be ween Exh1 and Exh2, he b ea hing gas mix u es used co esponded o PIO2o 73, 82, 92, 99,
and 142 mmHg (No moxia) and we e adminis e ed ollowing a double-blind design. Subjec s we e asked o pedal close o 80 pm. Howe e , when app oaching
exhaus ion, he pedaling a e was always educed.
F on ie s in Physiology | www. on ie sin.o g 3Augus 2016 | Volume 7 | A icle 333
To es-Pe al a e al. Oxygena ion E ec s on Muscle Ac i a ion a Fa igue
Oxygen Up ake and Hemoglobin Oxygen
Sa u a ion
Oxygen up ake was measu ed wi h a me abolic ca (Vmax
N29; Senso medics, Cali o nia, USA), calib a ed be o e each es
acco ding o he manu ac u e ins uc ions. Respi a o y a iables
we e analyzed b ea h-by-b ea h and a e aged e e y 10 s o
he analysis o ansi ions a exhaus ion. Hemoglobin oxygen
sa u a ion was es ima ed wi h a inge pulse oxime e (SpO2)
(OEM III module, 4549-000, Plymou h, MN).
Elec omyog aphy
Elec ical MA was moni o ed using su ace elec omyog aphy
(EMG) (Figu e 2). EMG signals we e con inuously eco ded
om he as us medialis and as us la e alis, as p e iously
epo ed (To es-Pe al a e al., 2016). Be o e he applica ion
o he EMG elec odes, he skin su ace was ca e ully sha ed,
and wiped wi h e hanol o educe skin impedance. Bipola
single di e en ial elec odes we e placed longi udinally on he
muscles ollowing he SENIAM ecommenda ions (Me le i and
He mens, 2000) and aped on he skin o minimize mo emen
a i ac s. The e e ence elec ode was placed on he skin o e
he ac omion. The posi ion o he elec odes was ma ked on he
skin wi h indelible ink, and hese e e ences we e used o p ecise
elec ode placemen in epea ed expe imen s.
The EMG signals we e acqui ed using a 16-channel eco ding
sys em (Myomoni o IV, Delsys Inc., Bos on, MA) a a sampling
a e o 1000 Hz using ec angula shaped (19.8 mm wide and
35 mm long) bipola su ace elec odes wi h 1 ×10 mm 99.9%
Ag conduc o s, and wi h an in e -conduc o dis ance o 10 mm
(DE-2.3 Delsys Inc.). The EMG da a we e il e ed wi h a high-
pass il e o 20 Hz and a low-pass il e o 450 Hz using a i h-
o de Bu e wo h il e . The sys em has an inpu impedance
o >1015pe 0.2pF o inpu capaci ance, a common mode
ejec ion a io o >80 dB, signal- o-noise a io <1.2 µV, and
a p e-ampli ie gain 1000 V/V ±1 %. Each pedal e olu ion
was de ec ed using an elec ogoniome e (Goniome e Biosignal
Senso S700 Join Angle Shape Senso ; Delsys Inc. Bos on) ixed
on he le knee and sampled a 500 Hz. The elec ogoniome e
was indi idually calib a ed aking as e e ences he knee angles
in ully ex ended and lexed posi ions. EMG and join mo emen
we e simul aneously eco ded by a po able de ice (Myomoni o
IV, Delsys Inc. Bos on) and wi elessly ansmi ed o a compu e
FIGURE 2 | Powe ou pu and EMG. Schema ic ep esen a ion o he powe ou pu (uppe panels), aw EMG (2nd ow), ec i ied EMG (3 h ow), and ec i ied and
smoo hed EMG (lowe panels), du ing he las 60 s o he con ol submaximal exe cise a 80 W in hypoxia (PIO2=73 mmHg), he las 10 s o he inc emen al exe cise
(IE) in se e e hypoxia (PIO2=73 mmHg), he i s 10 s o he ansi ion om a PIO2o 73 o 82 mmHg, he las 10 s o he IE a a PIO2o 82 mmHg, he i s 10 s in
no moxia and he las 10 s be o e ask ailu e in no moxia.
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To es-Pe al a e al. Oxygena ion E ec s on Muscle Ac i a ion a Fa igue
(EMGWo ks Wi eless applica ion and EMGWo ks Acquisi ion
3.7.1.3; Delsys, Inc. Bos on).
The EMG signal co esponding o each muscle con ac ion
was analyzed using code de eloped “in house” (Ma lab R2012b,
Ma hWo ks, Na ick, MA, USA). The EMG eco dings we e ull-
wa e ec i ied and smoo hed o p o ide an index o muscle
ac i a ion; he ampli ude cha ac e is ics we e analyzed ia
a e age RMS o a 25-ms mo ing window o he du a ion o he
con ac ion bu s . Con ac ion bu s onse and o se de ec ion
we e de e mined using 20% o he maximal EMGRMS ac i i y
o each con ac ion bu s as a e e ence (Baum and Li, 2003;
Hug and Do el, 2009; To es-Pe al a e al., 2014), a he han
a mean h eshold alue om 15 consecu i e con ac ion bu s s
(Ozgunen e al., 2010). This app oach yielded he same esul
as di ec , simple isual disc imina ion, wi h 100% de ec ion o
all con ac ion bu s s. Con ac ion iming was de ined as he
ime elapsed om he knee a is g ea es ex ension o he s a
o he con ac ion bu s , exp essed as a pe cen age o he ull
du a ion o each e olu ion. The EMGRMS eco ded du ing he
las minu e o a 2 min 80 W load (in hypoxia, PIO2=73
mmHg) was used o no malize he emaining EMGRMS da a.
Besides, we de ined a o al ac i i y index (TAI) as TAI =
EMGRMS ×bu s du a ion (ms) ×numbe o pedal s okes
du ing he pe iod o ime analyzed. The o al ac i i y index
is simila o he in eg a ed EMG signal, bu was compu ed
sepa a ely o each con ac ion bu s and excluded he baseline
EMG be ween con ac ion bu s s (To es-Pe al a e al., 2014).
The TAI eco ded du ing he las minu e o a 2 min 80 W
load (in hypoxia) was used o no malize he es o he TAI
alues.
The mean (MPF) and median (MdPF) powe spec um
equencies we e calcula ed using Fas Fou ie T ans o m
(Solomonow e al., 1990). All a iables we e epo ed as he mean
alues o he pedal s okes eco ded du ing he las 10 and 30 s o
he inc emen al exe cise. EMG da a a e epo ed sepa a ely o
as us medialis (VM) and la e alis (VL), and also as he a e age
o he wo muscles.
Calcula ion o he Imp o emen in SaO2
du ing he Fi s 10 s o he T ansi ions
The mean change in SaO2needed o explain he mean
imp o emen in VO2obse ed du ing he i s 10 s o he
ansi ion om hypoxia o highe a PIO2was calcula ed by
sol ing he Fick equa ion, using a e ial blood gasses and
he modilu ion ca diac ou pu da a ob ained in no moxia and
hypoxia (PIO2=73 mmHg) in pa allel in asi e expe imen s
pe o med by he same subjec s (Calbe e al., 2015a). Since
simila le els o peak ca diac ou pu we e eached in se e e
hypoxia and no moxia, i was assumed ha he le el o
ca diac ou pu eached a exhaus ion a in e media e PIO2
le els (i.e., 82, 92, and 99 mmHg) mus ha e been simila
o ha measu ed in no moxia. I was also assumed ha
ca diac ou pu emained unchanged du ing he i s 10 s o he
ansi ion, gi en he s abili y o hea a e du ing he ansi ions
and he high dependency o ca diac ou pu on he absolu e
exe cise in ensi y (Calbe and Lundby, 2009; Calbe e al., 2009a,
2015b), which emained unchanged du ing he i s 10 s o he
ansi ion.
S a is ics
No mal dis ibu ion o a iables was checked using he
Shapi o-Wilks es . Since a iables we e no mally dis ibu ed,
di e ences be ween es s a Exh1 we e de e mined using one-
way epea ed measu es analysis o a iance (ANOVA). The
Mauchly’s es o sphe ici y was un be o e he ANOVA and
in he case o iola ion o he sphe ici y assump ion he
deg ees o eedom we e adjus ed acco ding o he Huynh
and Feld es . Pai wise compa isons a speci ic ime poin s
we e pe o med wi h S uden ’s pai ed - es s and adjus ed o
mul iple compa isons wi h he Holm–Bon e oni me hod. Since
no signi ican di e ences we e obse ed a exhaus ion be ween
he ou es s in se e e hypoxia (PIO2=73 mmHg), hese
ou es s we e a e aged o ob ain a ep esen a i e alue o
exhaus ion a a PIO2o 73 mmHg. The same p ocedu e was
used o es o di e ences be ween he ou IE es s ending
in no moxia (Exh3). Simila esul s we e ob ained in he ou
es s a exhaus ion in no moxia (Exh3) and hence, he alues
ob ained in hese ou es s we e also a e aged o gene a e a single
alue ep esen ing no moxia. These wo a e ages we e compa ed
wi h S uden ’s pai ed - es s. The e ec o inc easing PIO2a
exhaus ion on all dependen a iables was assessed using a wo-
way ANOVA o epea ed measu es wi h wo ac o s: b ea hing
gas ( wo le els: p e- s. pos -swi ch o he new b ea hing
gas) and PIO2( ou le els), ollowed by pai wise compa isons
using S uden ’s pai ed - es s adjus ed o mul iple compa isons
wi h he Holm–Bon e oni me hod. The ela ionships be ween
changes in PIO2and he changes in he dependen a iables we e
es ed using linea eg ession analysis. To compa e he i s 10 s
o he ansi ion be ween he i s and he second ansi ion,
an a e age alue o he ou condi ions o each ansi ion was
calcula ed. This gene a ed a single alue pe subjec o he i s
and ano he unique alue pe subjec o he second ansi ion.
The wo ansi ions we e compa ed wi h a pai ed S uden ’s -
es . Values a e epo ed as he mean ±s anda d de ia ion
(unless o he wise s a ed). P≤0.05 was conside ed s a is ically
signi ican . All s a is ical analyses we e pe o med using SPSS
.15.0 o Windows (SPSS Inc., Chicago, IL) and Excel 2011
(Mic oso , Redmond, WA, USA).
RESULTS
Maximal Exe cise in Se e e Acu e Hypoxia
(PIO2=73 mmHg) and No moxia (PIO2=
142 mmHg)
As shown in Table 1, SpO2, powe ou pu a exhaus ion (Wmax),
VO2peak, pulmona y en ila ion a exhaus ion (VE), espi a o y
a e (RR), hea a e a exhaus ion (HR), end- idal O2p essu e
(PETO2), end- idal CO2p essu e (PETCO2), and ca bon dioxide
p oduc ion (VCO2) we e lowe du ing he las 30 s o exe cise in
se e e hypoxia han in no moxia, while he espi a o y exchange
a io (RER) was highe in hypoxia han in no moxia (all P
≤0.05).
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To es-Pe al a e al. Oxygena ion E ec s on Muscle Ac i a ion a Fa igue
TABLE 1 | E gospi ome ic and elec omyog aphic esponses du ing he
las 30 s o he inc emen al exe cise o exhaus ion in no moxia (PIO2≈
142 mmHg) and se e e hypoxia (PIO2≈73 mmHg).
Hypoxia (PIO2=No moxia P
73 mmHg)
FIO2(%) 10.8 ±0.07 20.8 ±0.04 <0.001
SpO2(%) 63.8 ±5.7 92.8 ±3.1 <0.001
Wmax (W) 170.5 ±17.9 213 ±19.7 <0.001
VO2peak (L.min−1) 2.28 ±0.19 3.44 ±0.43 <0.001
VE(L.min−1) 115.2 ±18.6 124.8 ±15.6 <0.001
RR (b ea hs.min−1) 50.6 ±7.0 55.9 ±7.1 <0.001
HR (bea s.min−1) 179.0 ±8.4 184.8 ±5.2 <0.001
PET O2(mmHg) 51.3 ±2.3 108.2 ±7.4 <0.001
PET CO2(mmHg) 28.1 ±2.5 30.8 ±3.1 <0.001
RER 1.34 ±0.13 1.05 ±0.06 <0.001
VCO2(L.min−1) 3.06 ±0.36 3.55 ±0.41 <0.001
RPM 71.9 ±4.1 68.4 ±4.2 0.08
VM RMS aw (µV) 111.2 ±38.6 128.3 ±42.4 <0.01
VL RMS aw (µV) 97.5 ±30.8 110.4 ±28.0 <0.01
A e age RMS aw (µV) 104.4 ±29.0 119.4 ±28.8 <0.005
VM RMSNz (A.U.) 178.1 ±35.2 209.2 ±58.4 <0.05
VL RMSNz (A.U.) 173.3 ±35.4 200.0 ±49.1 <0.005
A e age RMSNz (A.U.) 175.4 ±31.2 204.6 ±50.3 <0.01
VM TAINz (A.U.) 111.5 ±33.5 138.7 ±47.8 <0.005
VL TAINz (A.U.) 97.3 ±21.0 117.4 ±22.7 <0.001
A e age TAINz (A.U.) 102.9 ±25.5 126.7 ±30.9 <0.001
VM MPF (Hz) 89.8 ±16.9 85.2 ±16.6 <0.001
VL MPF (Hz) 89.6 ±16.5 85.5 ±17.1 <0.001
A e age MPF (Hz) 89.7 ±16.7 85.4 ±16.9 <0.001
VM MdPF (Hz) 71.3 ±12.1 69.2 ±11.8 0.06
VL MdPF (Hz) 70.6 ±12.1 68.9 ±12.2 0.06
A e age MdPF (Hz) 70.9 ±12.1 69.0 ±12.0 0.06
VM Bu s (ms) 305.4 ±51.5 334.3 ±34.8 <0.05
VL Bu s (ms) 283.0 ±34.5 306.2 ±26.7 <0.05
A e age Bu s (ms) 294.2 ±42.1 320.2 ±29.6 <0.05
FIO2, inspi a o y oxygen ac ion; SpO2, hemoglobin sa u a ion in capilla y blood
measu ed by pulse oxime y; Wmax, powe ou pu a exhaus ion; VO2, oxygen
consump ion; VE, pulmona y en ila ion; RR, espi a o y a e; HR, hea a e; PET O2, end-
idal O2p essu e; PET CO2, end- idal CO2p essu e; RER, espi a o y exchange a io;
VCO2, CO2p oduc ion; RPM, e olu ions pe minu e; VL, as us la e alis; VM, as us
medialis; RMS aw, aw oo mean squa e; RMSNz, no malized oo mean squa e; TAINz,
no malized o al ac i a ion index (a bi a y uni s, A.U.); MPF, mean powe equency;
MdPF, median powe equency; Bu s , con ac ion bu s du a ion. n =10.
Muscle ac i a ion, as e lec ed by VM and VL aw and
no malized RMS, o al ac i a ion index and con ac ion bu s
du a ion was 8–20% lowe in hypoxia han no moxia (P<0.05)
(Table 1). In con as , MPF was 5% lowe in no moxia han
hypoxia (P<0.001) and a simila end was obse ed o MdPF
(Table 1).
E ec o Inc eased PIO2on
ca dio espi a o y and EMG Va iables
Inc eased PIO2allowed o he con inua ion o exe cise du ing
41.9 ±19.8, 60.7 ±30.2, 72.9 ±52.0, and 170.5 ±70.8 s o
he ansi ion om a PIO2o 73 mmHg o placebo, 82, 92,
and 99 mmHg, espec i ely, (all P<0.05, compa ed o he end
exe cise in se e e acu e hypoxia). The e was a linea ela ionship
be ween he du a ion o he new oxygena ion phases and he
inc ease o PIO2( ime (s) =35.1+4.86·1PIO2;R2=0.955, P
<0.001, n=8), whe e 1PIO2 ep esen s he inc ease in PIO2in
mmHg (Figu e 3A). A simila ela ionship was ob ained be ween
endu ance ime and he es ima ed imp o emen in SaO2( ime (s)
=21.1+9.17·1SaO2;R2=0.973, P<0.001, n=8) (Figu e 3B).
Compa ed o he mean alues obse ed du ing he las 10 s
o exe cise in se e e hypoxia (PIO2=73 mmHg), PETO2,
and VO2we e inc eased, and RER educed du ing he i s
10 s ollowing he inc ease in oxygena ion (Tables 2 and 3).
SpO2was only signi ican ly inc eased in ansi ions o no moxia
(Table 3), in pa due o he slow esponse ime o he pulse
oxime e . These e ec s we e mo e accen ua ed he g ea e he
di e ence in PIO2be ween he hypoxic and he inc eased PIO2
condi ion.
T ansi ion om Se e e Hypoxia (PIO2o 73
mmHg) o Highe Le els o PIO2
VL and VM RMS aw, RMSNz and TAINz we e all enhanced
by inc easing he PIO2a exhaus ion (ANOVA main b ea hing
gas e ec P<0.05) (Table 2). VM and VL RMS aw, as well as
he VM-VL a e age RMS aw, we e inc eased by 5–10% when
he PIO2was aised om 73 o 92, o 99 mmHg (Table 2). VL
RMS aw and he VM-VL a e age RMS aw we e also inc eased
when he PIO2was aised om 73 o 142 mmHg (Table 3). MPF
and MdPF emained a he same le el wi h he inc ease o PIO2.
T ansi ion o No moxia
As depic ed in Table 3, inc easing PIO2 om di e en hypoxia
condi ions o no moxia was also associa ed o inc eased VM
and VL RMS aw and RMSNz, as well a VM TAINz and VM-
VL A e age TAINz (ANOVA b ea hing gas main e ec P<
0.05) (Table 3). When he da a om he wo condi ions wi h
g ea e le els o hypoxia (PIO2o 73 and 82 mmHg) we e
a e aged, inc easing PIO2a exhaus ion o no moxia signi ican ly
inc eased MA (RMS aw and RMSNz) and he no malized TAI
(P<0.05). Howe e , his was no he case when he da a om
he less hypoxic condi ions (PIO2o 92 and 99 mmHg) we e
a e aged, o which he ansi ion o highe PIO2did no esul
in signi ican ly g ea e muscle ac i a ion. In gene al, MPF and
MdPF emained a he same le el o changed sligh ly wi h he
ansi ion o an inc eased PIO2.
We also analyzed he 10 s comp ised be ween he 5 h and
he 15 h second a e he s a o he ansi ion and compa ed
hese 10 s wi h he las 10 s o he p eceding exe cise phase. The
esul s o his analysis we e essen ially simila o hose desc ibed
abo e, i.e., inc easing PIO2a exhaus ion esul ed in inc eased
MA (RMS aw and RMSNz), pa icula ly when a igue occu ed
a high le els o hypoxia (PIO2o 73 and 82 mmHg).
In gene al, he pedaling a e was augmen ed wi h inc eased
oxygena ion a he ansi ion om di e en le els o hypoxia
o no moxia, and consequen ly, he du a ion o he con ac ion
bu s s was educed (Table 3). A he same ime, he s a o he
F on ie s in Physiology | www. on ie sin.o g 6Augus 2016 | Volume 7 | A icle 333
To es-Pe al a e al. Oxygena ion E ec s on Muscle Ac i a ion a Fa igue
FIGURE 3 | Rela ionship be ween he du a ion o new oxygena ion phases wi h: (A) he inc ease o PIO2(1PIO2) and (B) he es ima ed imp o emen in
a e ial sa u a ion (1SaO2). G een ci cles: ansi ions om se e e hypoxia (PIO2=73 mmHg) o placebo ( e ical a ow) and mode a e hypoxia; ed ci cles:
ansi ions om di e en le els o hypoxia (PIO2o 73, 82, 92, and 99 mmHg) o no moxia. Each poin co esponds o he mean o 10 subjec s.
con ac ion bu s s occu ed sligh ly ea lie wi h an inc ease in
oxygena ion om a PIO2o 73 mmHg o no moxia.
The Fi s T ansi ion Compa ed wi h he
Second T ansi ion
In he i s ansi ion, he PIO2was inc eased om se e e hypoxia
(PIO2=73 mmHg) o less hypoxic le els, while du ing he
second ansi ion he PIO2was inc eased om di e en le els
o hypoxia o no moxia. We calcula ed a mean alue o he
ou PIO2condi ions o he i s ansi ion and compa ed i
wi h he mean alue calcula ed using he ou condi ions o he
second ansi ion, including in he analysis only he b ea h-by-
b ea h da a collec ed du ing he i s 10 s o each ansi ion.
The mean PIO2du ing he i s and second ansi ion was
84.3 ±2.1, and 137.5 ±3.0 mmHg, espec i ely, (P<0.001);
while SpO2was 64.1 ±4.8 and 72.0 ±4.7%, espec i ely, (P
<0.001). The mean exe cise in ensi y a which he i s and
second ansi ions occu ed was 170.5 ±17.9 and 173.5 ±16.3
W (P=0.08). The mean esponse o hea a e, pulmona y
en ila ion, espi a o y a e and idal olume we e simila in
bo h ansi ions (Figu es 4A–D, espec i ely). In con as , he
PETCO2, PETO2, VO2, and VCO2we e highe du ing he second
ansi ion (Figu es 4E–H, espec i ely).
Muscle ac i a ion was 6% highe du ing second compa ed
o he i s ansi ion, as e lec ed by he VM, VL, and VM-VL
a e age RMS aw alues (P<0.05) (Figu e 5A). Simila esul s
we e ob ained o he VM and VM-VL a e age RMSNz, which
we e 8 and 7% highe du ing he second compa ed o he i s
ansi ion, espec i ely (P<0.05) (Figu e 5B). The VM, VL,
and VM-VL a e age TAINz alues we e 8-10% highe du ing
he second han he i s ansi ion (P<0.05) (Figu e 5C). VM,
VL, and VM-VL a e age mean and median powe equencies
we e 4–6% lowe du ing he second han he i s ansi ion (P
<0.001) (Figu es 5D and E). The s a o he bu s occu ed
sligh ly ea lie in he pedaling cycle du ing he second compa ed
o he i s ansi ion o he VM and VM-VL a e age alues,
espec i ely, (P<0.05) (Figu e 5F). The du a ion o he bu s
and he mean pedaling a es we e simila du ing bo h ansi ions
(P>0.56) (Figu es 5G and H).
Impo ance o he Magni ude o he
Change in PIO2and he P e-exis ing Le el
o Hypoxia on he Response o an Inc ease
in PIO2
As e lec ed in Figu e 6, he changes o PETO2, VO2, he du a ion
o he bu s s and pedaling a e (PR) we e linea ly ela ed o he
inc ease in PIO2as shown in he equa ions:
1VO2=0.0277 ·1PIO2−0.0514(R2=0.990;
P<0.001;n=8);Equa ion 1, (Figu e 6A)
1PETO2=0.654 ·1PIO2−0.852(R2=0.997;
P<0.001;n=8);Equa ion 2, (Figu e 6B)
1BD =16.33 −1.127 ·1PIO2(R2=0.941;
P<0.001;n=8);Equa ion 3, (Figu e 6E)
1PR =0.082 −1.122 ·1PIO2(R2=0.917;
P<0.001;n=8);Equa ion 4, (Figu e 6F)
Whe e 1VO2is exp essed in L·min−1;1PETO2and 1PIO2in
mmHg; BD in ms, and PR in pm.
The VM-VL a e age RMS aw was linea ly ela ed o he
inc ease in PIO2, bu only in he ansi ions om a PIO2o
73 mmHg o a highe PIO2[1RMS aw (µV) =1.945 +
0.449 ·1PIO2(R2=0.915; P<0.05, n=4)] (Figu e 6C). This
ela ionship was los a e no maliza ion o he RMS (Figu e 6D).
Placebo E ec s
In he placebo ansi ion, subjec s belie ed ha hey we e
ecei ing no moxia upon exhaus ion in se e e hypoxia; howe e ,
hey we e main ained a he same le el o hypoxia. No signi ican
changes we e obse ed in MA (RMSNz and TAINz) as a
consequence o his placebo ea men (Table 2).
F on ie s in Physiology | www. on ie sin.o g 7Augus 2016 | Volume 7 | A icle 333
To es-Pe al a e al. Oxygena ion E ec s on Muscle Ac i a ion a Fa igue
TABLE 2 | Ca dio espi a o y esponses du ing he las 10 s o an inc emen al exe cise o exhaus ion in se e e hypoxia (PIO2=73 mmHg) and du ing he
i s 10 s o oxygena ion wi h di e en gas mix u es.
Exhaus ion S a o Exhaus ion S a o Exhaus ion S a o Exhaus ion S a o
PIO2=73 PIO2=99 PIO2=73 PIO2=92 PIO2=73 PIO2=82 PIO2=73 PIO2=73
mmHg mmHg mmHg mmHg mmHg mmHg mmHg mmHg
FIO2(%) 10.78 ±0.10 13.92 ±0.23c10.82 ±0.12 12.45 ±0.75c10.78 ±0.06 12.01 ±0.25c10.79 ±0.08 10.79 ±0.20¶§‡
SpO2(%) 62.4 ±5.2 63.1 ±5.5 64.3 ±5.5 65.1 ±5.7 63.5 ±5.8 63.6 ±5.9 64.7 ±4.9 64.4 ±5.7‡
Wmax (W) 172.0 ±23.5 172.0 ±23.5 170.0 ±21.6 170.0 ±21.6 168.0 ±16.9 168.0 ±16.9 172.0 ±21.5 172.0 ±21.5
VO2peak (L.min−1) 2.32 ±0.17 2.81 ±0.46b2.23 ±0.25 2.53 ±0.34a2.33 ±0.15 2.45 ±0.27T2.27 ±0.29 2.29 ±0.32¶§‡
VE(L.min−1) 118.2 ±23.7 111.8 ±20.8 114.8 ±26.3 116.8 ±22.6 117.5 ±16.4 116.4 ±15.1 114.8 ±14.7 116.8 ±15.6
RR (b ea hs.min−1) 51.7 ±9.2 48.1 ±7.2 51.3 ±8.5 50.7 ±8.2 51.5 ±8.4 51.1 ±7.6 51.3 ±7.0 52.3 ±7.7
HR (bea s.min−1) 179.0 ±10.2 179.3 ±10.1 180.5 ±8.2 181.0 ±7.4 177.3 ±7.4 177.5 ±7.2 180.6 ±7.9 180.8 ±8.3¶
PET O2(mmHg) 51.4 ±3.0 62.9 ±5.1c51.7 ±3.1 58.1 ±6.3c51.4 ±2.9 56.1 ±3.9c51.6 ±2.0 51.9 ±2.0¶§‡
PET CO2(mmHg) 27.3 ±2.9 27.3 ±4.3 28.3 ±2.9 28.4 ±2.7 27.4 ±3.7 27.6 ±3.0 28.5 ±2.3 28.2 ±2.4
RER 1.32 ±0.17 1.16 ±0.15T1.36 ±0.15 1.28 ±0.13 1.32 ±0.15 1.28 ±0.15 1.36 ±0.14 1.37 ±0.17§
VCO2(L.min−1) 3.06 ±0.42 3.01 ±0.44 3.03 ±0.48 3.12 ±0.41 3.07 ±0.29 3.06 ±0.28 3.08 ±0.41 3.11 ±0.39
RPM 63.6 ±9.4 66.3 ±10.3 68.5 ±7.0 71.3 ±11.4 67.1 ±9.5 68.2 ±12.0 71.2 ±7.8 70.0 ±9.3
VM RMS aw (µV) 105.9 ±37.2 119.3 ±43.5c106.3 ±42.6 112.2 ±38.1a113.5 ±42.7 120.6 ±50.2T97.2 ±43.0 99.7 ±42.6¶‡
VL RMS aw (µV) 108.8 ±38.4 119.1 ±39.9c97.3 ±48.9 102.0 ±49.2a115.8 ±49.9 114.1 ±45.1 85.9 ±35.5 87.4 ±40.6¶
A e age RMS aw (µV) 107.4 ±29.1 119.2 ±33.4c101.8 ±41.5 107.1 ±39.1b114.7 ±39.2 117.3 ±40.6 91.5 ±34.9 93.6 ±38.0¶‡
VM RMSNz (A.U.) 176.2 ±48.1 195.8 ±56.9c178.0 ±58.4 191.2 ±57.2a180.9 ±50.4 187.6 ±41.7 164.8 ±67.2 168.6 ±64.2¶
VL RMSNz (A.U.) 182.5 ±55.5 199.6 ±52.2c160.2 ±38.8 171.1 ±35.5a189.6 ±67.0 185.6 ±45.4 151.7 ±49.2 152.3 ±51.7¶‡
A e age RMSNz (A.U.) 179.4 ±49.8 197.7 ±52.5c169.1 ±47.0 181.2 ±45.0a185.2 ±56.4 186.6 ±40.2 158.2 ±56.8 160.5 ±56.9¶‡
VM TAINz (A.U.) 39.6 ±17.6 44.5 ±19.5b35.6 ±14.8 38.0 ±12.5 37.1 ±14.1 37.6 ±11.1 33.5 ±13.3 35.5 ±14.1¶
VL TAINz (A.U.) 36.8 ±13.5 41.2 ±14.4c30.2 ±9.7 32.8 ±7.1 37.1 ±12.6 35.8 ±8.7 29.3 ±8.8 31.6 ±14.0¶
A e age TAINz (A.U.) 38.2 ±15.4 42.8 ±16.9c32.9 ±11.8 35.4 ±9.5 37.1 ±13.2 36.7 ±9.6 31.4 ±10.6 33.6 ±13.3¶
VM MPF (Hz) 96.0 ±24.8 95.1 ±24.2 89.2 ±22.8 91.5 ±23.9 91.2 ±17.3 89.8 ±15.0 84.9 ±15.5 83.6 ±13.8
VL MPF (Hz) 97.0 ±27.0 96.0 ±27.5 88.9 ±22.6 90.2 ±23.2 91.2 ±17.3 89.5 ±15.5 84.9 ±15.9 83.5 ±14.4
A e age MPF (Hz) 96.5 ±25.9 95.5 ±25.7 89.1 ±22.7 90.9 ±23.5 91.2 ±17.3 89.6 ±15.3 84.9 ±15.7 83.5 ±14.1
VM MdPF (Hz) 76.3 ±17.1 76.9 ±17.1 70.3 ±15.7 72.7 ±14.7 70.8 ±13.2 71.8 ±11.6 66.9 ±10.3 66.2 ±10.5
VL MdPF (Hz) 77.8 ±19.7 77.6 ±20.0 69.8 ±15.9 70.9 ±15.0 70.7 ±13.2 71.4 ±12.0 66.4 ±10.8 65.6 ±10.2
A e age MdPF (Hz) 77.0 ±18.3 77.3 ±18.4 70.0 ±15.8 71.8 ±14.7 70.8 ±13.2 71.6 ±11.7 66.7 ±10.5 65.9 ±10.3§
VM Bu s (ms) 361.5 ±110.1 349.9 ±85.9 310.7 ±88.3 305.1 ±81.2 310.3 ±62.5 304.9 ±94.7 309.3 ±80.7 318.2 ±74.7
VL Bu s (ms) 343.2 ±91.7 324.8 ±81.7 297.8 ±55.6 300.1 ±70.7 310.2 ±59.7 303.9 ±91.5 300.0 ±63.7 316.5 ±86.6
A e age Bu s (ms) 352.4 ±95.3 337.3 ±79.0 304.3 ±71.3 302.6 ±75.4 310.2 ±60.8 304.4 ±93.0 304.7 ±71.0 317.4 ±76.5
VM Timing (%) 48.8 ±3.8 47.6 ±4.2a49.4 ±2.5 49.1 ±3.2 49.4 ±2.3 49.3 ±2.9 47.9 ±3.9 48.3 ±4.2‡
VL Timing (%) 50.7 ±2.1 50.0 ±2.3 50.2 ±2.3 49.9 ±2.5 50.3 ±2.1 50.3 ±2.4 49.5 ±2.9 49.6 ±3.0
A e age Timing (%) 49.7 ±2.6 48.8 ±2.7 49.8 ±2.3 49.5 ±2.7 49.8 ±2.2 49.8 ±2.6 48.7 ±3.4 49.0 ±3.5
FIO2, inspi a o y oxygen ac ion; SpO2, hemoglobin sa u a ion in capilla y blood measu ed by pulse oxime y; Wmax, powe ou pu a exhaus ion; VO2, oxygen consump ion; VE,
pulmona y en ila ion; RR, espi a o y a e; HR, hea a e; PET O2, end- idal O2p essu e; PET CO2, end- idal CO2p essu e; RER, espi a o y exchange a io; VCO2, CO2p oduc ion;
RPM, e olu ions pe minu e; VL, as us la e alis; VM, as us medialis; RMS aw, aw oo mean squa e; RMSNz, no malized oo mean squa e; TAINz: no malized o al ac i a ion index
(a bi a y uni s, A.U.); MPF, mean powe equency; MdPF, median powe equency; Bu s , con ac ion bu s du a ion; Timing: s a o ac i a ion exp essed as pe cen age o o al
e olu ion du a ion. aP<0.05; bP<0.01; cP<0.001; and TP<0.1 (FIO2=73 mmHg s. new gas mix u e). ¶P<0.05 ANOVA b ea hing gas swi ch main e ec ; §P<0.05 ANOVA
oxygena ion le el main e ec ; ‡P<0.05 ANOVA b ea hing gas swi ch x oxygena ion le el in e ac ion; n =10.
DISCUSSION
This s udy shows ha MA du ing he las 10–30 s o an IE
o exhaus ion is lowe in SAH han in no moxia, while a
exhaus ion in mode a e hypoxia MA was simila o ha obse ed
a exhaus ion in no moxia. We ha e shown ha du ing exe cise
a di e en le els o hypoxia, inc easing PIO2a exhaus ion
wi h no moxic o less hypoxic gas mix u es apidly elie es
a igue and allows o he con inua ion o exe cise. This e ec is
accompanied by inc eased MA only when he le el o hypoxia
du ing he exe cise elici ing exhaus ion was se e e (PIO2o 73
mmHg, equi alen o an al i ude close o 5200 m) and he PIO2
was inc eased o 92 mmHg o highe and he es ima ed SaO2
o 70% o highe . Ne e heless, he close linea ela ionship
be ween he inc ease in MA (a e age o VM and VL RMS aw)
and he inc ease in PIO2(Figu e 6C) indica es ha du ing
exe cise in SAH any small inc ease in PIO2could ha e a posi i e
e ec on muscle ac i a ion. This is also suppo ed by he ac
ha du ing he i s 10 s o he ansi ions, MA was highe
du ing he second han he i s ansi ion, despi e he ac
F on ie s in Physiology | www. on ie sin.o g 8Augus 2016 | Volume 7 | A icle 333
To es-Pe al a e al. Oxygena ion E ec s on Muscle Ac i a ion a Fa igue
TABLE 3 | Ca dio espi a o y esponses du ing he las 10 s o an inc emen al exe cise o exhaus ion in di e en le els o hypoxia (PIO2=73, 82, 92, and
99 mmHg) and du ing he i s 10 s o oxygena ion o no moxia (PIO2=142 mmHg).
Exhaus ion S a o Exhaus ion S a o Exhaus ion S a o Exhaus ion S a o
PIO2=99 No moxia PIO2=92 No moxia PIO2=82 No moxia PIO2=73 No moxia
mmHg mmHg mmHg mmHg
FIO2(%) 14.42 ±0.12 20.26 ±0.46c13.41 ±0.39 19.99 ±0.53c11.98 ±0.21 19.90 ±0.62c10.91 ±0.44 20.02 ±0.74c¶§‡
SpO2(%) 78.2 ±4.1 80.2 ±5.3a70.4 ±6.7 73.4 ±6.8c67.6 ±4.5 68.2 ±4.2b64.7 ±4.8 66.3 ±6.20a¶§‡
Wmax (W) 180.0 ±21.1 180.0 ±21.1 172.0 ±19.3 172.0 ±19.3 170.0 ±17.0 170.0 ±17.0 172.0 ±21.5 172.0 ±21.5
VO2peak (L.min−1) 2.93 ±0.25 3.89 ±0.68b2.87 ±0.28 4.15 ±0.45c2.48 ±0.32 3.99 ±0.52c2.37 ±0.30 4.05 ±0.59c¶§‡
VE(L.min−1) 119.9 ±18.1 116.1 ±25.6 118.6 ±19.0 117.3 ±16.7 110.8 ±24.5 109.5 ±17.8 117.6 ±17.5 113.6 ±21.2
RR (b ea hs.min−1) 53.5 ±7.1 51.2 ±5.7 53.2 ±7.0 52.6 ±6.0 49.6 ±8.6 49.5 ±5.6 52.7 ±7.2 52.2 ±7.7
HR (bea s.min−1) 182.2 ±7.9 182.1 ±8.7 182.7 ±6.2 182.9 ±6.2 178.6 ±7.0 178.5 ±6.5 180.9 ±7.9 180.5 ±7.9
PET O2(mmHg) 71.3 ±2.6 96.4 ±9.9c64.4 ±3.1 90.6 ±13.4c56.7 ±3.4 91.4 ±12.2c51.8 ±2.1 92.3 ±11.5c¶§‡
PET CO2(mmHg) 29.0 ±2.9 30.5 ±3.0a29.0 ±2.9 30.1 ±2.5a28.7 ±3.6 29.5 ±3.5a28.3 ±2.4 30.2 ±2.7a
RER 1.13 ±0.08 0.92 ±0.10c1.12 ±0.08 0.87 ±0.12c1.21 ±0.11 0.84 ±0.10c1.35 ±0.14 0.90 ±0.15c¶§‡
VCO2(L.min−1) 3.28 ±0.28 3.29 ±0.51 3.21 ±0.34 3.25 ±0.29 3.00 ±0.47 3.02 ±0.37 3.13 ±0.40 3.16 ±0.41§
RPM 61.7 ±9.0 67.0 ±12.5 63.8 ±11.4 69.5 ±10.2b61.9 ±11.3 68.1 ±9.4T58.3 ±12.6 65.6 ±13.9T¶
VM RMS aw (µV) 116.9 ±45.3 122.7 ±46.6 120.2 ±42.5 119.8 ±39.2 120.1 ±49.4 125.3 ±47.6 102.6 ±47.0 108.4 ±44.3
VL RMS aw (µV) 116.5 ±38.1 123.6 ±43.3 107.3 ±52.5 110.8 ±52.6 118.4 ±50.2 122.7 ±52.9 87.2 ±36.1 94.5 ±37.0b¶
A e age RMS aw (µV) 116.7 ±32.5 123.2 ±35.9 113.8 ±42.6 115.3 ±40.3 119.3 ±41.6 124.0 ±43.1 94.9 ±37.5 101.5 ±36.3a¶
VM RMSNz (A.U.) 182.1 ±53.9 191.7 ±57.8 204.3 ±70.8 205.8 ±68.7 189.5 ±57.3 197.9 ±51.7 172.9 ±70.7 184.7 ±77.1¶
VL RMSNz (A.U.) 195.4 ±52.6 206.8 ±66.6 177.8 ±41.3 183.4 ±43.3 194.5 ±70.0 199.4 ±57.5 155.9 ±55.7 167.3 ±53.4a¶
A e age RMSNz (A.U.) 188.7 ±43.9 199.2 ±52.7 191.1 ±53.8 194.6 ±50.8 192.0 ±61.4 198.6 ±51.6 164.4 ±62.0 176.0 ±63.9¶
VM TAINz (A.U.) 39.9 ±15.7 43.6 ±16.2T42.8 ±19.2 40.6 ±11.2 42.1 ±17.0 42.6 ±14.5 36.1 ±14.4 38.0 ±16.4¶
VL TAINz (A.U.) 43.2 ±19.3 42.4 ±14.4 34.1 ±9.0 35.3 ±7.2 40.5 ±15.2 40.9 ±12.8 32.5 ±13.8 34.1 ±15.6
A e age TAINz (A.U.) 41.5 ±17.1 43.0 ±15.1 38.4 ±13.4 37.9 ±8.4 41.3 ±15.9 41.7 ±13.5 34.3 ±13.5 36.0 ±15.5¶
VM MPF (Hz) 87.4 ±20.1 84.9 ±20.6 84.7 ±20.2 86.0 ±21.0 88.5 ±14.6 87.0 ±16.6 81.8 ±15.2 81.7 ±16.4
VL MPF (Hz) 71.4 ±15.8 85.3 ±21.9c85.7 ±19.4 85.6 ±21.8 88.1 ±15.0 86.3 ±16.9 81.9 ±15.5 82.1 ±16.1¶‡
A e age MPF (Hz) 79.4 ±17.8 85.1 ±21.2b85.2 ±19.8 85.8 ±21.4 88.3 ±14.8 86.6 ±16.7 81.8 ±15.3 81.9 ±16.2‡
VM MdPF (Hz) 70.9 ±16.2 69.9 ±16.2 67.5 ±13.6 68.7 ±15.2 72.1 ±11.8 70.3 ±12.2 65.0 ±10.6 66.1 ±13.2
VL MdPF (Hz) 71.4 ±15.8 68.8 ±16.6a67.9 ±13.6 68.1 ±16.2 71.4 ±12.1 69.2 ±12.7 65.5 ±11.0 65.9 ±12.5
A e age MdPF (Hz) 71.1 ±16.0 69.3 ±16.4 67.7 ±13.6 68.4 ±15.6 71.8 ±11.8 69.8 ±12.3 65.3 ±10.8 66.0 ±12.8
VM Bu s (ms) 375.6 ±127.2 363.0 ±130.0 377.9 ±196.2 317.6 ±83.8 372.8 ±102.7 322.0 ±73.8a367.5 ±85.1 319.2 ±72.1a¶
VL Bu s (ms) 381.7 ±120.6 321.3 ±83.7a343.6 ±109.4 309.1 ±73.1T366.7 ±107.3 315.0 ±72.4T371.4 ±97.1 309.3 ±60.0a¶
A e age Bu s (ms) 378.6 ±113.0 342.2 ±92.2T360.8 ±150.4 313.3 ±77.6 369.8 ±104.6 318.5 ±58.9a369.5 ±88.6 314.2 ±63.9a¶
VM Timing (%) 49.1 ±3.4 46.3 ±7.7 48.2 ±3.5 48.1 ±4.4 48.6 ±3.0 47.8 ±3.6 49.4 ±3.4 47.4 ±4.3a¶
VL Timing (%) 49.5 ±3.6 50.2 ±2.2 49.4 ±2.5 49.7 ±2.1 50.4 ±1.6 49.4 ±2.4 50.5 ±2.3 49.4 ±2.8
A e age Timing (%) 49.3 ±3.0 48.3 ±4.2 48.8 ±2.7 48.9 ±3.0 49.5 ±2.1 48.6 ±2.8T50.0 ±2.8 48.4 ±3.4a¶
FIO2, inspi a o y oxygen ac ion; SpO2, hemoglobin sa u a ion in capilla y blood measu ed by pulse oxime y; Wmax, powe ou pu a exhaus ion; VO2, oxygen consump ion; VE,
pulmona y en ila ion; RR, espi a o y a e; HR, hea a e; PET O2, end- idal O2p essu e; PET CO2, end- idal CO2p essu e; RER, espi a o y exchange a io; VCO2,CO2p oduc ion;
RPM, e olu ions pe minu e; VL, as us la e alis; VM, as us medialis; RMS aw, aw oo mean squa e; RMSNz, no malized oo mean squa e; TAINz: no malized o al ac i a ion index
(a bi a y uni s, A.U.); MPF, mean powe equency; MdPF, median powe equency; Bu s : con ac ion bu s du a ion; Timing, s a o ac i a ion exp essed as pe cen age o o al
e olu ion du a ion. aP<0.05; bP<0.01; cP<0.001; and TP<0.1 (FIO2=73 mmHg s. new gas mix u e). ¶P<0.05 ANOVA b ea hing gas swi ch main e ec ; §P<0.05 ANOVA
oxygena ion le el main e ec ; ‡P<0.05 ANOVA b ea hing gas swi ch x oxygena ion le el in e ac ion: n =10.
ha bo h ansi ions occu ed a compa able exe cise in ensi ies.
Mo eo e , ou in es iga ion has also demons a ed ha an
inc ease in MA a e he inc ease o PIO2a a igue in hypoxia is
no indispensable o he e gogenic e ec s elici ed by he inc ease
o PIO2. Collec i ely, ou esul s sugges ha se e e hypoxia
dep esses he capaci y o he cen al ne ous sys em o ac i a e
he muscula u e du ing whole-body exe cise o exhaus ion, by
a mechanism ha can be swi ly e e sed by inc easing he
PIO2.
Se e e Hypoxia Reduces he Le el o
Muscle Ac i a ion A ainable du ing
Inc emen al Exe cise o Exhaus ion
In suppo o a cen al p edominance o ask ailu e mechanisms
is he apid elie o a igue wi h he inc ease o PIO2, e.g., when
subjec s a exhaus ion a e asked o con inue he exe cise once
he hypoxic gas mix u e hey a e b ea hing is swi ly swi ched
o no moxic oom ai (Calbe e al., 2003a) o hype oxic gas
(Amann e al., 2007). This concu s wi h he demons a ion o a
F on ie s in Physiology | www. on ie sin.o g 9Augus 2016 | Volume 7 | A icle 333