the cardiopulmonary exercise test ( cpx ) is the gold standard for evaluating the cause of 
 exercise intolerance in patients with pulmonary and cardiac disease1 .
various tests are available , each being more or less 
 suitable as a stressor of a particular component of the patient s pathophysiology . according 
 to the american thoracic society / american college of chest physicians statement on cpx ,
the 
 incremental exercise test ( iet ) is most widely used in clinical practice , but the constant 
 high - intensity exercise test ( cet ) is gaining popularity because of its clinical 
 applicability , particularly for monitoring responses to a spectrum of therapeutic 
 interventions2 . the iet is used to calculate the aerobic threshold ( at)3 , respiratory compensation point , and o2 at peak work rate 
 ( pw ; vo2 peak or vo2 max)4 . on the other hand ,
the cet is useful for the analysis of gas 
 exchange kinetics5 and dynamic 
 hyperinflation6 .
in addition , the change 
 in time to the limit of tolerance in cet ( also known as endurance time [ et ] ) at 7580% load 
 of pw has been shown to provide a more sensitive index of improvement than pw , or vo2 

most recent studies of 
 cet have used an 80% load of pw7 , 8 , 11,12,13 .
vo2 is determined by the variables in the fick 
 equation : vo2 = q  ( cao2  
 cvo2 ) where q is the cardiac output ( co ; the product of heart rate [ hr ] and stroke volume [ sv ] ) , 
 and cao2 and cvo2 are the o2 contents of arterial and mixed 
 venous blood , respectively .
the vo2 value during cet reaches vo2 max , 
 as assessed by iet , in the case of symptom limit and load ( higher critical power ) during 
 cet14 , 15 .
however , we conjectured that even if both tests reach vo2 
 peak at exhaustion , the component ratios are different because of the different 
 exercise load patterns .
we hypothesized that cet would reach a higher o2 
 extraction at exhaustion because of progressive fatigue due to a higher atp turnover 
 rate16 , 17 .
therefore , the purpose of this study was to compare the 
 physiological changes during iet and cet at 80% load of pw in healthy human subjects .
twenty - five young men ( mean  standard deviation [ sd ] ; age = 23.3  1.48  years , height = 
 169.4  5.9  cm , body mass = 61.6  6.4  kg ) participated in this study .
the subjects were informed of the potential 
 risks and discomfort associated with the experiments before giving their written consent to 
 participate in this study , which was approved by the ethical review committee of kio 
 university ( koryo - cho , japan ) and performed in accordance with the ethical principles of the 
 declaration of helsinki .
an iet ( work rate of 
 25  w / min , pedal revolution rate of 60  rpm / min ) was performed using a braked cycle ergometer 
 ( lode ; corival , groningen , the netherlands ) on the first day of testing for the 
 determination of estimated pw and other respiratory and metabolic factors . on a separate 
 day
, subjects returned to the laboratory for a cet at 80% of pw ( pedal revolution rate of 
 60  rpm / min ) . during both tests , we measured physiological responses , namely , ventilatory , metabolic , and 
 cardiovascular responses , and muscle oxygenation .
ventilatory and metabolic variables were 
 recorded breath - by - breath with a gas analyzer ; cardiovascular responses were recorded with 
 finapres ; and muscle oxygenation was recorded by near - infrared spectroscopy ( nirs ) .
ventilatory and metabolic variables were recorded breath - by - breath with a computerized 
 metabolic cart ( metamax3b ; cortex , leipzig , germany ) .
oxygen uptake ( vo2 ) , carbon 
 dioxide output ( vco2 ) , minute ventilation ( ve ) , the ventilator equivalent for 
 carbon dioxide ( ve / vco2 ) , the ratio of dead space to tidal volume ( vd / vt ) , 
 end - tidal carbon dioxide pressure ( petco2 ) , the respiratory exchange 
 ratio ( rer ) , and hr were determined from values averaged every 30 s. noninvasive continuous arterial systolic blood pressure ( sbp ) was measured beat - to - beat 
 using the finapres finger cuff ( portepress ; fms , amsterdam , the netherlands ) on the index 
 finger along with a height correction system attached to the top of the finger .
the finapres 
 finger cuff uses the volume - clamp technique to measure finger arterial pressure18 . together with beatscope software 
 ( beatscope easy ; fms , amsterdam , the netherlands ) , the finapres finger cuff determines left 
 ventricular sv ; sv and hr values are used to calculate co. oxygenation changes in the vastus lateralis muscle were evaluated by nirs ( bom - l1trw ; 
 omegawave , tokyo , japan ) at rest and during exercise .
the nirs probe was placed on the 
 muscle approximately 1420  cm above the knee joint .
this instrument uses 3 light - emitting 
 diodes ( wavelengths : 780 , 810 , and 830  nm ) and calculates the relative tissue levels of 
 oxygenated hemoglobin ( o2hb ) , deoxygenated hemoglobin ( hhb ) , and total hemoglobin 
 ( thb ) according to the beer - lambert law .
the absorption coefficients of hemoglobin ( hb ) are 
 based on previously reported data19 , and 
 individual values are proportional to the hb levels .
levels of o2hb , hhb , and thb 
 are expressed in mol / l , but hb concentrations are expressed in arbitrary units ( au ) because 
 they do not represent actual physical volumes .
we calculated muscle o2 saturation 
 ( smo2 ) from the o2hb and thb values with the following formula : 
 smo2 ( % ) = ( o2hb / thb )  100 .
data analysis was performed using spss version 19.0 statistical software ( spss 
 inc . ,
the peak value for each of the measurements was defined as the mean 
 of values acquired during the last 30  s of the test .
comparisons between the iet and cet results were analyzed using the paired t - test . a 
 value of p < 0.05 was considered to be statistically significant .
table 1table 1 . the results of exercise capacityvariablesincremental exercise test ( iet)vo2max ( l / min)2.550.47peak watt : pw ( w)202.922.6hr max ( bpm)185.38.58vo2at ( l / min)1.320.22at ( w)98.718.8constant high - intensity exercise test 
 ( cet)work rate ; 80% of pw ( w)162.318.1exercise tolerance time ( sec)634.373.7variables are presented as meansd .
vo2 : oxygen uptake , hr : heart rate , 
 at : anaerobic threshold shows the exercise capacity , and table 
 2table 2 .
comparison of exercise testing variables at end of exercise between iet and 
 cetvariablesietcetvo2 ( l / min)2.550.472.630.41vco2 ( l / min)2.920.432.710.37*ve ( l / min)68.912.367.512.1ve / vco224.83.1826.72.92*vd / vt0.110.030.130.04*petco245.26.2642.54.30*rer1.170.101.210.12hr ( bpm)185.38.58186.55.01sbp ( mmhg)199.0916.67186.0124.27*sv ( ml)96.9317.8582.220.07co ( l / min)16.13.2313.233.02*tpr0.680.280.570.25o2hb ( a.u.)7.631.687.241.88hhb ( a.u.)9.072.869.532.74**thb ( a.u.)16.82.9016.773.21smo2 ( % ) 46.40.0943.60.09**p value of the paired t - test : * p<0.05 , * * p<0.01 .
iet : incremental exercise 
 test , cet : constant high - intensity exercise test , vo2 : oxygen uptake , 
 vco2 : carbon dioxide output , ve : minute ventilation , ve / vco2 : 
 ventilator equivalent for carbon dioxide , vd / vt : ratio of dead 
 space to tidal volume , petco2 : end - tidal carbon dioxide 
 pressure , rer : respiratory exchange ratio , hr : heart rate , sbp : arterial blood 
 pressure , sv : stroke volume , co : cardiac output , o2hb : oxygenated 
 hemoglobin , hhb : deoxygenated hemoglobin , thb : total hemoglobin , smo2 : 
 muscle oxygen saturation shows the results of the comparison of end - exercise responses of the iet and 
 cet .
all subjects completed the iet , reaching exhaustion levels ; hrmax was 94.2  
 4.23% of the age - predicted value , and rer was 1.17  0.0120 .
the vo2 max of iet was 2.55  0.47 l / min , and there was 
 no significant difference in vo2 between the iet and cet .
sbp and co were 
 significantly higher in the iet than in the cet ( p < 0.05 ) .
hhb was significantly higher 
 and smo2 was significantly lower in the cet than in the iet ( p < 0.01 ) .
vo2 : oxygen uptake , hr : heart rate , 
 at : anaerobic threshold p value of the paired t - test : * p<0.05 , * * p<0.01 .
iet : incremental exercise 
 test , cet : constant high - intensity exercise test , vo2 : oxygen uptake , 
 vco2 : carbon dioxide output , ve : minute ventilation , ve / vco2 : 
 ventilator equivalent for carbon dioxide , vd / vt : ratio of dead 
 space to tidal volume , petco2 : end - tidal carbon dioxide 
 pressure , rer : respiratory exchange ratio , hr : heart rate , sbp : arterial blood 
 pressure , sv : stroke volume , co : cardiac output , o2hb : oxygenated 
 hemoglobin , hhb : deoxygenated hemoglobin , thb : total hemoglobin , smo2 : 
 muscle oxygen saturation
therefore , we believe that the iet was 
 performed until exhaustion and that vo2 reached vo2 max .
in addition , 
 there were no significant differences in vo2 between the iet and cet .
these results suggest that 
 the iet might have a higher cardiac load than the cet .
this hypothesis is supported by the 
 fact that vo2 max during the iet is mainly limited by the cardiovascular system 
 in normal healthy subjects21 and that 
 muscle blood flow is correlated linearly and positively with work rate22 , 23 .
further , the 
 iet would demand a greater o2 delivery than the cet . by the end of the exercises , hhb in
hhb is considered 
 to be similar to o2 extraction24 , 25 , and the increasing rate of hhb in venous 
 occlusion can be used as a muscle o2 consumption index26 . in addition , smo2 was significantly lower in 
 the cet than in the iet .
smo2 signals provide a reliable estimate of the dynamic 
 balance between o2 supply and o2 consumption in the area of 
 investigation27 .
these findings suggest 
 that the cet has a higher muscle o2 extraction rate than the iet at the end of 
 exercise .
interestingly , the findings may be explained by hhb kinetics at the end of the 
 tests . at the end of the iet , the hhb response displays a slowdown or plateau point28,29,30 , whereas at the end of the cet , the hhb 
 response displays a progressive rise following the hhb 
we found that 
 the hhb showed these trends in the present study ( fig . 

an example of deoxygenated hemoglobin ( hhb ) kinetics during exercise tests in a 
 representative subject . ) .
the hhb slow component has been reported to be strongly correlated with lactate 
 concentrations during running33 .
lactic 
 acidosis favors a greater release of o2 from hb due to the rightward displacement 
 of the oxyhemoglobin dissociation curve ( bohr effect ) , consequently facilitating 
 o2 extraction from the blood .
the physiological mechanisms of these hhb 
 responses in relation to the iet and cet are still not fully understood and can not be 
 explained using the results of the present study , but it is likely that metabolic changes in 
 the muscles play a role .  
an example of deoxygenated hemoglobin ( hhb ) kinetics during exercise tests in a 
 representative subject . in conclusion
, the present study demonstrated that there are differences in physiological 
 responses between the iet and cet at the end of exercise .
although both exercise tests 
 induced similar responses with respect to vo2 , the factors determining 
 vo2 changes were different : cardiac load was lower and muscle o2 
 extraction was higher in cet than iet .
these results suggest that if both tests produce a 
 similar vo2 value , vo2 in the iet would have a higher ratio of cardiac 
 output than the cet , and vo2 in the cet would have a higher ratio of 
 o2 extraction than the iet at the end of exercise
. these findings may be useful 
 for further assessment of individual exercise - limiting factors .
   [ purpose ] vo2 is expressed as the product of cardiac output and o2 
 extraction by the fick equation . during the incremental exercise test and constant 
 high - intensity exercise test , vo2 results in the attainment of maximal 
 o2 uptake at exhaustion . 
 however , the differences in the physiological 
 components , cardiac output and muscle o2 extraction , have not been fully 
 elucidated . 
 we tested the hypothesis that constant exercise would result in higher 
 o2 extraction than incremental exercise at exhaustion . 
 [ subjects ] twenty - five 
 subjects performed incremental exercise and constant exercise at 80% of their peak work 
 rate . [ methods ] ventilatory , cardiovascular , and muscle oxygenation responses 
 were 
 measured using a gas analyzer , finapres , and near - infrared spectroscopy , respectively . 
 
 [ results ] vo2 was not significantly different between the incremental exercise 
 and constant exercise . however , cardiac output and muscle o2 saturation were 
 significantly lower for the constant exercise than the incremental exercise at the end of 
 exercise . 
 [ conclusion ] these findings indicate that if both tests produce a similar 
 vo2 value , the vo2 in incremental exercise would have a higher 
 ratio of cardiac output than constant exercise , and vo2 in constant exercise 
 would have a higher ratio of o2 extraction than incremental exercise at the end 
 of exercise . 
INTRODUCTION
SUBJECTS AND METHODS
RESULTS
DISCUSSION