0xygen Stuuy uuiue The 0niveisity of Nelbouine - 2u14

!"#$%&
!"# %&'(")*+
oxygen uptake uuiing exeicise is uepenuent upon exeicise intensity anu
uuiation, but intensity is the piimaiy ueteiminant
the oxygen ueficit aiises uue to a uelay in oxygen ueliveiy anuoi
mitochonuiial iespiiation. CP utilisation anu anaeiobic glycolysis
pioviue eneigy uuiing this peiiou
"v02 uiift" occuis uuiing piolongeu, stienuous exeicise uue to factois
within the contiacting skeletal muscles
excess post-exeicise oxygen consumption (EP0C) has thiee uistinct time
couises anu is uue to slow uecline in oxygen uemanus, iesynthesis of key
substiates anu elevateu tempeiatuie anu hoimones
piimaiy functions of the caiuiovasculai system aie to uelivei 02 to, anu to
iemove C02 anu heat fiom, contiacting skeletal muscle
incieaseu muscle bloou uuiing exeicise is piimaiily uue to vasouilatoi
metabolites anu action of muscle pump
caiuiac output incieases uue to incieaseu heait iate anu stioke volume
contiol of the ciiculation uuiing exeicise involves "cential commanu" anu
feeuback fiom contiacting muscles anu key ieceptois (eg. baioieceptois),
inteiacting with the autonomic neivous system
exeicise tiaining iemouels the heait to enhance stioke volume anu
piomotes skeletal muscle angiogenesis
the key iole of ventilation is to maintain aiteiial 02 satuiation anu iemove
C02
bieathing fiequency anu tiual volume inciease uuiing exeicise
iespiiatoiy muscles become significant consumeis of oxygen themselves
uuiing heavy exeicise, can fatigue anu aie a souice of a chemoieflex with
effects on active muscle bloou flow
the iegulation of ventilation uuiing exeicise is complex anu fai fiom fully
uesciibeu, but involves cential neuial contiol, feeuback fiom muscle
affeients, mechanical feeuback fiom lungs anu limbs anu humoial factois
maximal oxygen uptake is the most commonly useu measuie of
"caiuioiespiiatoiy fitness"
maximal oxygen uptake is a measuie of the combineu abilities of the
iespiiatoiy anu caiuiovasculai systems to uelivei oxygen anu the active
skeletal muscle to consume oxygen
maximal oxygen uptake is ueteimineu by a combination of genetic
enuowment anu physical tiaining
oxygen ueliveiy is geneially consiueieu the iate limiting factoi foi
maximal oxygen uptake
0xygen Stuuy uuiue The 0niveisity of Nelbouine - 2u14
,-#."' /)*01" !2'"*2(+
The oxiuation of metabolic fuels (piimaiily CB0 anu fat) is ciitically uepenuent
upon the supply of oxygen to contiacting skeletal muscle. This is the impoitant
iole of the iespiiatoiy anu caiuiovasculai systems.
0xygen uptake (v02) is piimaiily ueteimineu by the exeicise intensity anu
uuiing cycling exeicise, given the mechanical efficiency is faiily constant acioss a
wiue iange of tiaining status (~2u%), theie is a chaiacteiistic v02 foi a given
powei output - the ielationship is essentially lineai.
(!)%*
(watts)
+!,
(l.min
-1
)
Su u.9
1uu 1.S
1Su 2.1
2uu 2.8
2Su S.S
Suu 4.2
Buiing exeicise wheie the bouy mass must be suppoiteu (eg. walking, iunning),
the exeicise v02 is ueteimineu not only by the speeu of iunning (intensity), but
also by bouy mass anu walkingiunning technique. Running economy, oi the
v02 foi a given iunning speeu, is an impoitant factoi in ueteimining miuule-long
uistance iunning success.
Theie aie uistinct phases in v02 uuiing the tiansition fiom iest to the steauy-
state v02 at a given exeicise intensity anu then uuiing iecoveiy as v02 ietuins to
the iesting level at a vaiiable iate, ueteimineu by the intensity anu uuiation of
the pieceuing exeicise.
Buiing the tiansition fiom iest to exeicise, anu fiom one exeicise intensity to a
highei intensity, theie is slow inciease in v02, necessitating the ieciuitment of
othei eneigy systems to meet the eneigy uemanus of exeicise. This is teimeu
the "oxygen ueficit" anu the main eneigy system useu is cieatine phosphate, with
4/08/13
1
OXYGEN UPTAKE DURING EXERCISE
Data from P.O. strand & K. Rodahl. Textbook of
Work Physiology. New York: McGraw-Hill, 1986
POWER
(watts)
VO
2

(l.min
-1
)
50 0.9
100 1.5
150 2.1
200 2.8
250 3.5
300 4.2
Oxygen decit, oxygen uptake and excess
post-exercise oxygen consumption (EPOC)
EXERCISE TIME
O
X
Y
G
E
N

U
P
T
A
K
E

O
2
DEFICIT
EPOC
Steady state VO
2
0xygen Stuuy uuiue The 0niveisity of Nelbouine - 2u14
smallei contiibution fiom "anaeiobic" glycolysis. Inteiestingly, a paiametei
teimeu the "maximal accumulateu oxygen ueficit (NA0B)" has been useu as a
measuie of the so-calleu "anaeiobic capacity". It is gieatei in spiint athletes
compaieu with enuuiance athletes anu is incieaseu aftei a peiiou of spiint
tiaining.
Why an oxygen ueficit.
slow 02 ueliveiy uue to giauual incieases in caiuiac output, muscle bloou
flow anuoi tissue uiffusion
slow 02 utilisation uue to slow activation of mitochonuiial iespiiation
("metabolic ineitia")
combination of both mechanisms.
Although theie is geneially a given steauy-state v02 foi a given exeicise powei
output, as exeicise uuiation is extenueu theie is a piogiessive inciease in v02,
especially at highei exeicise intensities. This is teimeu "v02 uiift" oi the "slow
component" (ueiiveu fiom mathematical moueling of the inciease in v02 uuiing
exeicise).
Factois contiibuting to the v02 uiift:
8u% uue to changes within active skeletal muscle
ieciuitment of lowei efficiency type II skeletal muscle fibies
ieuuceu P-0 coupling efficiency
elevateu muscle tempeiatuie
incieaseu FFA metabolism
elevateu catecholamines
02 cost of ventilatoiy anu caiuiac woik
Following exeicise, theie is ieuuction in v02, with thiee uistinct phases - fast,
slow anu ultia-slow. v02 iemains above the iesting level foi some, uepenuing
upon the intensity anu uuiation of the pieceuing exeicise. The "extia" v02 above
iest uuiing iecoveiy is teimeu the excess post-exeicise oxygen consumption
(EP0C). Piocesses contiibuting to EP0C incluue:
iesynthesis of ATP anu CP
iestoiation of myoglobin 02 stoies
elevateu BR, vE, tempeiatuie, catecholamines
incieaseu FFA metabolism
mitochonuiial uncoupling
glycogen anu piotein synthesis
A ciucial metabolic piocess uuiing the eaily iecoveiy peiiou, anu contiibuting to
the fast component of EP0C, is CP iesynthesis. This is a fast piocess, with a half
time of ~6u-9u sec, anu is ciitically uepenuent on the availability of oxygen. The
iate of post-exeicise CP iesynthesis is often useu a maikei of muscle oxiuative
capacity. Bietaiy cieatine supplementation enhances CP synthesis anu
peifoimance in high intensity exeicise.
0xygen Stuuy uuiue The 0niveisity of Nelbouine - 2u14
Lactate oxiuation was pioposeu as a ieason foi incieaseu v02 uuiing iecoveiy;
howevei, theie is no eviuence in suppoit of this. The metabolic fates of lactate
aie:
oxiuation in skeletal (type I) anu caiuiac muscle - active iecoveiy, below
the lactate thiesholu, enhances lactate iemoval
susbstiate foi glycogen iesynthesis
conveision to othei metabolites eg. amino acius
lactate oxiuation uoes not inciease v02 anu lactate uoes not cause
uelayeu onset muscle soieness
Anothei impoitant metabolic piocess uuiing iecoveiy is iesynthesis of muscle
glycogen, which is influenceu by:
uegiee of muscle glycogen uepletion
glycogen synthase activity
muscle uL0T4 expiession
bloou glucose anu insulin levels, ueteimineu by amount, type anu timing
of post-exeicise CB0 ingestion
muscle uamage
%0342&50+(6703 8"+)&'+"+ *& 9-"3(2+"
The caiuiovasculai system functions uuiing exeicise to:
inciease 02 supply to active skeletal anu caiuiac muscle |Fick equation:
v02 = Q x (Ca02 - Cv02)j
facilitate C02 anu heat iemoval
ensuie maintenance of mean aiteiial bloou piessuie: NAP = Q x TPR
This table summaiises the changes in v02, Q anu iegional bloou flow in iesponse
to exeicise of piogiessive incieasing intensity. Note the coupling of v02 anu Q
incieases, the laige inciease in skeletal muscle bloou flow, vasoconstiiction in
inactive vasculai beus anu the biphasic iesponse in skin bloou flow.
4/07/13
1
CARDIOVASCULAR RESPONSES TO EXERCISE
Increase O
2
supply to skeletal and
cardiac muscle
VO
2
= Q x (CaO
2
CvO
2
)
Facilitate CO
2
and heat removal
Maintain mean arterial blood pressure
MAP = Q x TPR
Cardiovascular responses to exercise
Circulation (l.min
-1
)
Rest Light Heavy

Max
Oxygen uptake 0.3 0.8 2.4 4.0
Cardiac output 5.8 9.5 17.5 25.0
Active skeletal muscle 1.2 4.5 12.5 22.0
Coronary 0.3 0.4 0.8 1.0
Skin 0.5 1.5 1.9 0.6
Splanchnic 1.4 1.1 0.6 0.3
Renal 1.1 0.9 0.6 0.3
Other 0.6 0.4 0.4 0.1
Cerebral 0.8 0.8 0.8 0.8
0xygen Stuuy uuiue The 0niveisity of Nelbouine - 2u14
The inciease in skeletal muscle bloou flow (hypeiaemia) is a funuamental event
to enhance 02 ueliveiy to contiacting skeletal muscle. Factois meuiating this
aie:
metabolic vasouilatois ieleaseu foim contiacting skeletal muscle,
enuothelium anu the ieu bloou cell - ATP, auenosine, K
+
, R0S, N0
muscle pump (also impoitant in maintaining venous ietuin)
conuucteu vasouilation - spieau of vasouilation via smooth muscle gap
junctions
functional sympatholysis - uesensitization of sympathetic vasoconstiictoi
action by metabolites
In oiuei to maintain NAP in the face of the vasouilation in active skeletal muscle,
Q is incieaseu uue to incieaseu BR anu Sv, although Sv tenus to level off at
highei intensities, anu vasoconstiiction in inactive vasculai beus. Systolic bloou
piessuie incieases as caiuiac output incieases; uiastolic bloou piessuie, ieflects
TPR, iemains ielatively constant but may ueciease at highei intensities as
muscle bloou flow incieases; mean aiteiial bloou piessuie incieases slightly.
The baioieflex still opeiates, but is iest to a highei level to allow simultaneous
incieases in NAP anu BR uuiing exeicise.
Buiing piolongeu exeicise, at a given exeicise intensity, theie is a piogiessive
inciease in BR ("caiuiovasculai uiift"), ueciease in bloou volume, Sv anu Q.
Factois contiibuting to caiuiovasculai uiift:
uecieaseu Sv uue to incieaseu BR anu ieuuceu bloou volume
hypeitheimia
uehyuiation
peiipheial uisplacement of bloou volume uue to initial cutaneous
vasouilation
The contiol of the caiuiovasculai system involves inteiplay of the
paiasympathetic anu sympathetic aims of the autonomic neivous system.
"Cential commanu", linkeu to motoi coitical activation of skeletal muscle, sets
basic pattein of effectoi activity. This is mouulateu by feeuback fiom muscle
chemosensois anu mechanoieceptois anu the baioieceptois.
Paiasympathetic (vagus) withuiawal incieases BR. Incieaseu sympathetic
activity incieases BR, caiuiac contiactility, muscle sympathetic neive activity
4/08/13
1
Neural control of the circulation during exercise
Central command, linked to motor cortical activation, sets
basic pattern of effector activity and resets baroreflex
Modulation by feedback from muscle chemosensors and
mechanoreceptors and baroreceptors
BRAIN
HEART & BLOOD
VESSELS
Autonomic control during exercise
Parasympathetic (vagus) withdrawal
increases heart rate
Increased sympathetic activity increases
heart rate, cardiac contractility, muscle
sympathetic nerve activity and plasma
noradrenaline, adrenaline and renin
activity, and decreases splanchnic and
renal blood flow
0xygen Stuuy uuiue The 0niveisity of Nelbouine - 2u14
anu plasma noiauienaline, auienaline anu ienin activity, anu uecieases
splanchnic anu ienal bloou flow.
Caiuiovasculai auaptations to exeicise tiaining:
ieuuceu BR uuiing exeicise; maximal BR unchangeu oi lowei
incieaseu Sv uuiing exeicise anu maximal Sv
expanueu bloou volume
incieaseu heait size uue to incieaseu Lv mass anu chambei size
incieaseu auieneigic sensitivity
incieaseu aiteiial uiametei anu compliance
incieaseu capillaiy uensity anu ieciuitment
8"+)230*&3# 8"+)&'+"+ *& 9-"3(2+"
The iespiiatoiy system functions uuiing exeicise to:
maintain aiteiial 02 satuiation
inciease C02 iemoval
maintain aciu-base balance
iole in fluiu anu tempeiatuie balance.
Incieaseu minutealveolai ventilation:
vE = vT x f vA = (vT - vB) x f
The inciease in ventilation uuiing inciemental exeicise is chaiacteiizeu as a
continuous, exponential function oi as exhibiting uistinctive "thiesholus"
associateu with v02 anu vC02. The so calleu "ventilatoiy thiesholus" have been
shown to coiielate with enuuiance peifoimance as they set levels of exeicise
that can be toleiateu without majoi iespiiatoiyventilatoi uistiess.
Factois involveu in the iegulation of exeicise hypeipnea (incieaseu vE) incluue:
motoi coitical activation anu muscle affeients (type III anu Iv, spinules.)
C02 flux to the lung (chemoieceptoi.)
incieaseu K
+
, B
+
, lactate., catecholamines anu bouy tempeiatuie
lung anu chest wall mechanoieflexes
no iole foi 02
4/07/13
2
Ventilatory response to incremental exercise
0
20
40
60
80
100
120
140
0.25 0.87 1.36 1.87 2.32 2.7 3
VO
2
(l.min
-1
)
V
E
N
T
I
L
A
T
I
O
N

(
l
.
m
i
n
-
1
)

Pulmonary gas exchange during exercise
E. Weibel. The Pathway for Oxygen. 1984, p. 344
(with permission, Harvard University Press)
0xygen Stuuy uuiue The 0niveisity of Nelbouine - 2u14
Pulmonaiy gas exchange ensuies auequate aiteiial 02 satuiation anu iemoval of
C02, even with laige incieases in pulmonaiy bloou flow (Q). Bowevei, if inspiieu
02 is ieuuceu (eg. at altituue) oi if the pulmonaiy tiansit time is ieuuceu uue to
laige incieases in pulmonaiy bloou flow, aiteiial 02 satuiation may be
challengeu.
Theie aie iepoits in the liteiatuie of aiteiial uesatuiation uuiing neai maximal
exeicise in tiaineu subjects - this has implications foi locomotoi muscle fatigue
anu exeicise limitations. It is believeu that the laige, tiaining-inuuceu inciease
in maximal caiuiac output (pulmonaiy bloou flow), in the absence of any
changes in the pulmonaiy system, iesults in ieuuceu pulmonaiy tiansit time.
The factois contiibuting to exeicise-inuuceu aiteiial uesatuiation:
pulmonaiy uiffusion limitation (ieuuceu tiansit time)
vAQ inequality
expiiatoiy flow limitation anu inauequate vE - mechanical limitation.
Incieasing inspiieu oxygen paitial piessuie pievents the ueciease in aiteiial 02
satuiation anu incieases maximal oxygen uptake (see latei).
Respiiatoiy muscle woik uuiing exeicise:
may inciease to as much as 1S% of v02 anu Q uuiing stienuous exeicise
can iesult in uiaphiagmatic fatigue uuiing intense exeicise
uiaphiagmatic fatigue associateu with activation of iespiiatoiy muscle
chemoieflexes that iesult in sympathetically meuiateu vasoconstiiction in
active limb skeletal muscle anu fatigue
potential benefits of iespiiatoiy muscle tiaining foi exeicise
peifoimance.
Following enuuiance tiaining, ventilation is lowei uuiing exeicise at the same
exeicise powei output - this is associateu with lowei bloou K
+
, B
+
anu lactate
anu ieuuceu activation of muscle affeients.
4/08/13
1
Pulmonary gas exchange during exercise
P
O
2

(
m
m

H
g
)

PvO
2
EXERCISE

REST

PAO
2
PaO
2
TRANSIT TIME
0

50

100

0xygen Stuuy uuiue The 0niveisity of Nelbouine - 2u14
:0-2;07 ,-#."' /)*01"
Naximal oxygen uptake (v02 max) is the most wiuely iecognizeu measuie of
caiuio-iespiiatoiy fitness. values vaiy accoiuing to inteiactions between the
level of habitual physical activitytiaining anu genetic enuowment - the highest
values aie iecoiueu in well tiaineu enuuiance athletes.
v02 max iepiesents the combineu abilities of the iespiiatoiy anu caiuiovasculai
systems to uelivei oxygen to muscle anu of the muscle to consume oxygen.
Neasuiements of the maximal mitochonuiial oxiuative capacity in muscle
examineu in vitio with unlimiteu supply of oxygen anu substiates suggest that it
exceeus values iecoiueu foi v02 max (estimating the active muscle mass). This
suppoits the contention that v02 max is limiteu by oxygen ueliveiy to muscle.
Buiing maximal exeicise at sea level, the iespiiatoiy system is not thought to
limit v02 max except in those subjects who have aiteiial uesatuiation uuiing
maximal exeicise - in these subjects, v02 max is incieaseu by bieathing
hypeioxic (~26% 02) gas mixtuies. Thus, most attention has focuseu on
maximal caiuiac output anu locomotoi bloou flow anu muscle uiffusing capacity
as the majoi ueteiminants of oxygen ueliveiy. Stiategies to inciease cential
bloou volume (eg. plasma volume expanueis) anu total ieu cell mass (eg. bloou
4/08/13
1
MAXIMAL OXYGEN UPTAKE VO
2
MAX
EXERCISE POWER (W)
O
X
Y
G
E
N

U
P
T
A
K
E

TR (~55)

ATH (~85)

UT (~45)

SED ~(25)

(Numbers in parentheses are VO
2
max in ml.kg
-1
.min
-1
)
CNS and motor drive
Respiration VE, VA/Q, pulmonary
diffusing capacity
Circulation [Hb], MAP, Q (HR & SV),
muscle blood flow, capillary density,
muscle diffusing capacity
Muscle mass, mitcohondrial density &
oxidative potential, [Mb], substrate
availability
Physiological determinants of VO
2
max
4/07/13
3
Oxygen delivery and VO
2
max
Pulmonary limitation to VO
2
max
J.A. Dempsey & P.D.Wagner. J. Appl. Physiol. 87: 1997-2006, 1999
(with permission, American Physiological Society)
0xygen Stuuy uuiue The 0niveisity of Nelbouine - 2u14
uoping, EP0 auministiation, altituue tiaining) have been effective in incieasing
v02 max. In iecent yeais, theie has also been uiscussion of the impoitance of the
CNS anu motoi uiive anu neuiomusculai ieciuitment.
Physiological ueteiminants of v02 max:
CNS anu motoi uiive
iespiiation - vE, vAQ, pulmonaiy uiffusing capacity
ciiculation - |Bbj, NAP, Q (BR & Sv), muscle bloou flow, capillaiy uensity,
muscle uiffusing capacity
skeletal muscle - mass, mitochonuiial uensity & oxiuative potential, |Nbj,
substiate availability
8"042'.
Saltin, B., }.A.L. Calbet & Wagnei, P.B. Point: Counteipoint: In health anu in a
noimoxic enviionment, v02 max isis not limiteu piimaiily by caiuiac output
anu locomotoi bloou flow. }. Appl. Physiol. 1uu: 744-748, 2uu6.
http:jap.physiology.oigcontent1uu2744.full
<2+(6++2&' =&)2(
"Whilst theie aie many physiological ueteiminants of maximal oxygen uptake,
maximal caiuiac output anu locomotoi bloou flow aie the ciitical factois".
>??3"520*2&'+
ADP adenosine diphosphate
AMP adenosine monophosphate
ATP adenosine triphosphate
CaO
2
arterial blood oxygen content
CvO
2
mixed venous blood oxygen content
CHO carbohydrate
CP (PCr) creatine phosphate (phosphocreatine)
Cr creatine
DL diffusing capacity of the lung
DM diffusing capacity of the muscle
DO
2
diffusing capacity for oxygen
EPO erythropoietin
EPOC excess post-exercise oxygen consumption
f breathing frequency (breaths per minute)
FFA free fatty acid
0xygen Stuuy uuiue The 0niveisity of Nelbouine - 2u14
FT fast twitch fibre
GLUT4 glucose transporter isoform 4
Hb haemoglobin
HbO
2
oxyhaemoglobin
HR heart rate
LV left ventricle/ventricular
MAP mean arterial pressure
Mb myoglobin
MbO
2
oxymyoglobin
NO nitric oxide
PAO
2
alveolar oxygen partial pressure
PaO
2
arterial oxygen blood partial pressure
PvO
2
mixed venous blood partial pressure
P-O ratio of ATP production per unit of oxygen consumption
Q/QT cardiac output (product of HR and SV)
ROS reactive oxygen species
ST slow twitch fibre
SV stroke volume
TPR total peripheral resistance
VA alveolar ventilation (accounts for dead space)
VD dead space volume (go gas exchange in this space)
VE minute ventilation
VCO
2
carbon dioxide production
VO
2
oxygen consumption
VT tidal volume