JOURNALOF APPLIED PHYSIOLOGY

Vol. 39, No. 1, July 1975. Printed in U.S.A.

Effect of changes in arterial oxygen content

on circulation and physical performance

B. EKBLOM, R. HUOT, E. M. STEIN, AND A. T. THORSTENSSON

Department of Physiology, Gymnastik- och Idrottsh6gskolan, Stockholm, Sweden

EKBLOM, B., R. HUOT, E. M. STEIN, AND A. T. THORSTENSSON. and during 02 breathing and found that &lax was un-
Efect of changes in arterial oxygen content on circulation and physical affected by 02 breathing.
performance. J. Appl. Physiol. 39( 1) : 71-75. 1975.-To evaluate It was our purpose in this study to more completely
the effect of different levels of arterial oxygen content on hemo- investigate the hemodynamic adjustments to high and low
dynamic parameters during exercise nine subjects performed sub- oxygen states, using the dye-dilution method for determi-
maximal bicycle or treadmill exercise and maximal treadmill exer-
nations of cardiac output and the treadmill as the ergome-
cise under three different experimental conditions: I) breathing
ter for maximal work.
room air (control); 2) b reathing 50 y0 oxygen (hyperoxia) ; 3) after
rebreathing a carbon monoxide gas mixture (hypoxia). Maximal
oxygen consumption (Vo2 nlnx) was significantly higher in hy- SUBJECTS, METHODS, AND PROCEDURES
peroxia (4.99 l/ min) and significantly lower in hypoxia (3.80
l/min) than in the control experiment (4.43 l/min). Physical Subjects. The subjects were nine clinically healthy male
performance changed in parallel with Vo2 max. Maximal cardiac physical education students, regarded as moderately active
Output (Qmax) was similar in hyperoxia as in control but was as described earlier (6), mean age 27.0 yr (23-34 yr); with
significantly lower in hypoxia mainly due to a decreased stroke an average V02 mn&xof 4.43 l/min (3.784.91 l/min), cor-
volume. A correlation was found between Voz nlax and trans- responding to 58.0 ml/min per kg (52.5-64.3 ml/min
ported oxygen, i.e., CaOz X (illlax, thus suggesting that central per kg).
circulation k an important limiting factor for human maximal blethods. Submaximal exercise was performed on either
aerobic power. During submaximal work HR was decreased in a motor-driven treadmill (4 subj) or a mechanically
hyperoxia and increased in hypoxia. Corresponding Q values
braked Monark bicycle ergometer (5 subj). The subject
were unchanged except for a reduction during high submaximal
performed the same type of exercise in the three different
exercise in hyperoxia.
experiments. Maximal exercise was always done on the
treadmill. Heart rate (HR) was obtained from ECG,
submaximal and maximal exercise; carbon monoxide hypoxia;
50 y0 oxygen hyperoxia; oxygen uptake; cardiac output; stroke recorded for 15 s each minute during submaximal exercise
volume; heart rate; a-v 02 difference; pulmonary ventilation and continuously near the end of the maximal run. The
average HR from the 5th and the 6th min during sub-
maximal, and the peak value during maximal exercise
are given in RESULTS. Expired air was collected in at least
MAXIMAL AEROBIC POWER (Vo, max) is influenced by two consecutive bags during the last 2 min of each work
changes in the oxygen content of the arterial blood (Caoz). load. Volu me of exp ired air ( ‘iiE) was measu red in a Tissot
Decreasing the Caoa by acute exposure to high altitude or Spiro meter and gas samples were an alyzed on the Scho-
by breathing gas mixtures with a lowered oxygen concen-y lander apparatus. During the hyperoxia experiment gas
tration (for reviews see 3, 24), reducing the oxygen carry- samples were also taken from the inspired air mixture. In
ing capacity of the blood by inhalation of carbon monoxide the carbon monoxide (hypoxia) experiments the CO was
(8, 28, 35) or anemia (32), and hemodilution (7, 20) have withdrawn from a tank and introduced with a syringe
all experimentally been shown to decrease both the maxi- into a closed-circuit breathing apparatus to which the
mal oxygen uptake per minute and physical performance. subject was connected, and into which oxygen was fed as
On the other hand maximal cardiac output ((&ax) it was utilized. The subject rebreathed the CO mixture
during hypoxemic state is relatively unchanged compared for 15 min preceding the tests. The subjects did not re-
to normoxia (12, 33, 34). breathe the CO during the different work loads due to
Increasing Caoz by breathing gas mixtures with in- the high breathing resistance of this apparatus. Thus,
creased oxygen concentration (16, 26, 27), by raising the from rest to the second submaximal work load the HbCO
ambient air pressures ( 10, 36), or by increasing the Hb level decreased, due to the washout of CO. Before the
concentration of the blood (7) will increase Vo2 max. maximal run the subject rebreathed the CO again, as
Nielsen and Hansen (27) state that this increased VO:! max described earlier (8).
cannot only be explained by an increased Cao2, and that In the hyperoxia experiments the oxygen-rich gas mix-
cardiac function must also have been positively influenced. ture (about 50 70 02 in Nz) was continuously supplied
Hughes et al. (18) measured cardiac output using the CO2 from a tank to a specially constructed Douglas bag from
rebreathing method during maximal exercise at normoxia which the subject was breathing. This arrangement made
71
 72 EKBLOM, HUOT, STEIN, AND THORSTENSSON

it possible to avoid large pressure changes and to adapt TABLE 1. Blood measurements at rest and
the gas supply to the demand. during submaximal and maximal exercise
--- -~
Cardiac output (Q) was measured with the dye-dilution mWp
technique, using indocyanine green (CardioJGreen) as an Pao2, Paco,, S”Oz, Caoz, Hct, Hb, HLa,
PH
indicator. For methodological details see Astrand et al.
mmHg nmHg % ml/l % s/l mM

(2) and Ekblom (6). Intra-arterial blood pressures were Rest

recorded during the 3rd min of exercise via an Elema Control 44 149
EMT 490 pressure transducer. Samples for determination hO.4 zk3.e
CO hy- 44 145
of hemoglobin concentration (Hb concn), hematocrit poxia zto.7 zt3.1
(Hct), carboxyhemoglobin (HbCO), lactates (HLa), oxy- (15.8 zt
gen saturation (Sao,), pH, oxygen tension (Pa&, and 0.5 %>
Hyperoxia 43 146
carbon dioxide tension (Pa& were taken from an ar- ~0.6 zt3.z
terial catheter during the last minutes of exercise. Hb Submax
I
concn was measured on a Beckman B spectrophotometer, Control 00 47 197 44 151 7.3! 1.3
calibrated against values obtained according to the van ztl.9 zt1.9 jz4.3 Ito. zt2. c &O.Ol *0.3
Slykc method. HLa was analyzed according to the Barker- CO hy- 96 47 177 46 156 7.3E 1.1
poxia ho.8 xt1.4 zt5.01 ~0.8 zt3.7 z.to.01 zto.2
Summerson method (4). Oxygen content was determined (14.1 zt
with the van Slyke method. PaOz and pH were measured 0.5 %>
Hyperoxia !60 45 !03 44 153 7.37 0.7
with electrode systems (Radiometer). Pace,, was deter-
fr3.9* rt2.1 xk3.61zizo.7 zk2.z zto.01 zto.l
mined with the Astrup technique. HbCO levels were Submax
determined on a CO-oximeter (Instrumentation Labora- II
Control 47 160 4.0
tory Inc. model 182). Means and standard deviations ho.8 zt3.c zto.9
were computed according to usual statistical methods. The CO hy- 46 158 4.9
differences between the three experiments were calculated poxia zt1.2 zk2.4 zto.9
(12.8 A
from intraindividual differences and the significance 0.5 %>
evaluated with the Student t-test. Level of significance Hyperoxia 45 156 2.0
was P < 0.05. kO.6 zt2.1 f0.3t

R-ocedures. Preliminary work tests werc> carried out in Maxima1 Zontrol 94 35 93 .96 47 160 7.23 13.0
all three types of experiments to familiarize the subjects fi2.8 zt1.9 fr1.2 It4.6 rto.7 rt3.7 zto.02 320.9
CO hy- 03 34 95* 86 48 167 7.21 15.0
with the test procedures and to determine &, Il,:tX for each poxia It1.1t rtl.2 *0.5t 34.9t rtO.8 h3.3 Iko.03 &0.8t
type of experiment (6). Measurements WYY: made during :13.3 =t
supine rest, during two upright subrnasi t nal work loads 0.6 %>
Hyperoxia !60 37 97 !ll 47 164 7.22 10.9
(the same load in all 3 types of experiments), correspond- &5.5t zt1.6 Ito. 9x4.01 zJzo.5 zt2.2 zto.01 +z2.0t
ing to about 30 % and 70 % of the individual’s normoxic -
ii0 2 nlax during maximal treadmill exercise. The speed -&lues are mcans & SE. * Saoz of unblocked Hb. t Significance in
difference I control study, P < 0.05.
and inclinatioil of the treadmill during the maximal
exercise were chosen so that the subject in the control
experiment would be exhausted in about 6 min. F’or six Oz-rich gas mixt,ure for about 45 min to achieve a gas
subjects the salne speed and inclination during the maxi- equilibrium between the inspired air and the tissues, as
mal exercise was used in the control, hypoxia, and hyper- evaluated from Nz and 02 measurements on expired air.
oxia experiments, while for three subjects the speed and The subjects were not allowed to breathe room air during
inclination in the hypoxia and hyperoxia experiments were the experiment, and special precautions were taken to
adjusted so that the work time should be about the same avoid leakage in the system, since a small leak would give
(6 min) in the three different experimental situations. a significant error in measured Vo,. Apart from the re-
During the maximal treadmill run the time to exhaustion breathing of 50 % 02 and CO during the supine rest that
was noted. The subjects did not know the work time and preceded all experiments after the catheters were inserted,
were not allowed to see any clock during the maximal run. the experimental protocol was exactly the same in all three
Before the resting measurements in the hypoxia experi- types of experiments. There was at least a 2-wk interval
ments the subjects rebreathed the CO gas mixture for 15 between experirnents.
min. The amount of CO was adjusted to give carboxy-
hemoglobin level of about 15 % of total hemoglobin. TO RESULTS
keep this HbCO level throughout the experiment an addi-
tional dose of CO had to be administered between the Mean values of all data are presented in Tables 1 and 2.
second submaxirnal and the maximal treadmill run. The The type of exercise did not affect the circulatory and
HbCO levels given in the RESULTS are the average of respiratory response at a given vo2. Therefore, the results
HbCO determinations on blood samples taken immedi- from the submaximal bicycle and treadmill tests are treated
ately before and after the determinations of 90, and Q. together.
The method and procedure to administrate the CO have The administration of CO resulted in an HbCO level of
been described earlier (8). 12.8-15.8%. In the hyperoxia experiments Paoz was about
In the hyperoxia experiment (50 % 02 in Nz) preliminary 260 mmHg compared to 103 mmHg during hypoxia and
experiments showed that the subjects had to rebreathe the 94 mmHg during control experiments. Oxygen content of
ARTERIAL OXYGEN CONTENT, CIRCULATION, AND PHYSICAL PERFORMANCE 73

TABLE 2. ~i?-Cuhby data at r&St and study ( 110 mmHg). (&,, , max SV, and max HR were
during submaximal and maximal exercise unchanged compared to the control study. Pulmonary
ventilation was reduced by 11.1 % (P < 0.05) in spite of
6 an increase in Vos m8X.
902, 0, I-9 sv, I? ejs MBP,
Z/min Z/min beats/ ml mmHg
min IQE
cd DISCUSSION

Rest Control 0.31 5.8 53 109 54.1 94 The aim of the present study was to measure the circula-
zto.01 zto.2 lt2.3 zt5.5 zt2.4 zt2.9 tory response to submaximal and maximal exercise in the
CO hypoxia 0.34 6.2 58 107 49.5 92 same subject after modification of the oxygen content of the
(15.8 zt 0.5%) zto.02 zto.4 ziz2.7 zt5.8 zt2.4 *3.7
arterial blood. This was accomplished by exposure to a)
Hyperoxia 0.37 10.1 5.5 53 105 60.9 87 CO, giving a blood HbCO level of about 15 % (hypoxia
zto.02 zto.9 zto.5 zt4.6 zt6.9 zt3.3 zt3.3 experiment), and b) 50 % 0 2 in the inspired air, giving a
Submax I
Control 1.33 31.3 12.4 94 131 110.2 101 Paoz of about 260 mmHg (hyperoxia experiment).
zho.07 zt7.5 zko.4 rt3.9 zlz4.4 rt5.5 zt5.7 Maximal physical performance was improved when the
CO hypoxia 1.35 31.2 13.0 101 129 104.8 103
(14.1 * 0.5%) ~0.06 Al.7 jzo.7 *4.0* zt6.2 zt2.4 zfz5.9
subjects were breathing 02-enriched air and decreased after
Hyperoxia 1.55 30.6 11.7 89 133 133.6 102 CO exposure. This change in physical performance is
z&0.08’ zt3.7 2tO.8 *5.1* zt6.9 &5.2* zt4.1 probably in large part secondary to the alteration in Vo2 max.
Submax II
Control 2.87 73.9 20.7 144 144 138.7 107 The 12.5 % increase in v02 max in the hyperoxic experi-
*o. 15 zt6.1 rtO.8 rt5.9 zt5.9 zt3.9 zt7.9 ments is of the same order of magnitude as reported by
CO hypoxia 2.76 77.6 20.8 154 137 132.9 107 Hughes et al. (18), Nielsen and Hansen (27), and Margaria
(12.8 2t 0.5%) zto. 15 zt8.9 z.tl.1 zt5.2* zt6.4* zt3.5 zJz5.9
Hyperoxia 2.95 62.2 19.1 130 144 154.2 113 et al. (25, 26) using 02 breathing and Fagraeus et al. (9, 10)
~0.16 *3.0* zto.9* zt5.5* A4.7 zt3.7* ~5.8 and Wyndham et al. (36) using raised ambient air pressure
Maximal
Control 4.43 157.3 28.2 184 154 158.4 110
to increase Po2, respectively.
zto. 14 zt7.3 rt1.3 zt3.5 zt8.0 zt3.9 zt5.4 The changes in v02 max in the three different experimen-
CO hypoxia 3.80 158.5 26.4 182 145 144.0 113 tal situations are caused mainly by the different volume of
(13.3 + 0.6%) *o. 17* h8.1 *1.2* zt3.1 &6.0* *3.1* zJz7.3
Hyperoxia 4.99 139.9 28.5 186 153 176.1 120
oxygen per minute transported to the tissues, i.e., Q X Cao,,
AO. 19* +5.4* zt1.3 zt4.8 b7.2 +4.3* rt3.7’ during maximal exercise (see Fig. 1). The importance of
t0he ‘Coffered” oxygen for J?o, lllslX was first pointed out by
Values are means =t SE. Work time (min) for 6 subj with the same work load:
control, 5.9 rt 0.4; HbCO, 3.8 rt 0.3*; high 02, 9.9 A 0.3.* * Significance in
Astrand et al. (2) and Stenberg et al. (33), later confirmed
difference to control study, P < 0.05. in other studies (e.g., 18, 3 1). This study confirms the high
correlation between ccoffered oxygen” and v02 max, in
the arterial blood differed significantly from control values spite of the wide variation of “offered oxygen” found in
during hypoxia and hyperoxia experiments (Table 1). Hb these experimental conditions.
concn and Hct were similar on comparable work loads In the hyperoxia experiment the 12.5 % increase (avg 9
under the three different experimental conditions. subj) in Tj02 max was accomplished by an increase in Ca9,
During hypoxia experiments the HR was higher during (7.4 %) but also by an increase in the peripheral utilization
the two submaximal exercises and the SV was lower during of the “offered” oxygen (see below). The iZ,,, during
the higher submaximal work load. VOW, pulmonary ventila- hyperoxia was unchanged, which thus confirms the results
tion, Q, and arterial blood pressure were similar to the from the study by Hughes et al. (18). On the other hand
control experiments at rest and during submaximal exercise. when Caos was decreased by CO the Q,,, was reduced by
During hyperoxia experiments the HR was lower at both 6.1 % (P < 0.05). The reduction of Q,,, was most pro-
submaximal work loads compared to control studies. Pul- nounced in the five subjects with an HbCO level higher
monary ventilation and Q was reduced during the high
submaximal work load. SV and arterial blood pressure b 1 I I I 1 1 -
MAXIMAL OXYGEN UPTAKE
were unchanged from control. I/min 0 ,I
00
Six subjects were tested at the same speed and inclina- //
00
tion of the treadmill during maximal exercises under the /?
0
0

three conditions. The work time averaged 5.9 min in the

5
control, 3.8 min in the hypoxia, and 9.9 min in the hyper-
oxia experiment.
During maximal exercise in the hypoxia experiment
VO 2 lllaX was reduced by 14.2 % (P < 0.05), SV by 5.4 %
(P < 0.05), and &ax by 6.1 % (P < 0.05), while max HR, 4-
arterial blood pressure, and pulmonary ventilation re-
mained unchanged. The average HbCO level for the whole 0 0
0
0

0
TRANSPORTED OXYGEN
group was 13.3 %. In the five subjects with an HbCO level 0
0
0’ max 6 x CaO 2 I/min
higher than 13 % the HR during maximal exercise was 1 L 1 1 1 1 ,
5 6 7
significantly reduced.
FIG. 1. Relation between oxygen uptake and transported oxygen,
In the hyperoxia experiment Vo2 mitX was increased by
i.e., Q X Cao,, during maximal running. Individual values (broken
12.6% (P < 0.05), and mean arterial blood pressure was lines) and means (solid line), at hypoxia, control, and hyperoxia ex-
also significantly higher ( 120 mmHg) than in the control periments, respectively (n = 8).
74 EKBLOM, HUOT, STEIN, AND THORSTENSSON

than 13 %. The average decrease in Q,,,,, in these subjects lower in the hyperoxia experiment compared to the control
was 7.7 % (P < 0.05). Tl lis is in contrast to the findings in situation, possibly indicating a more effective peripheral
the CO-hypoxia study by Vogel and Gleser (34) and the 02 utilization and/or distribution of Q in the hyperoxia
hypobaric hypoxia studies by Stenberg et al. (33), who situation.
both reported unchanged Qtllsx in hypoxia compared to During submaximal exercise at a given intensity the
normoxia. This discrepancy could be accounted for by heart rate was higher after CO exposure, which agrees
methodological differences such as bicycle instead of tread- with other studies on the effect of acute hypoxia (e.g., 8,
mill exercise (33) or the use of the same subjects for 12, 18, 28, 33, 35). In the hypoxia experiment Q was un-
two maxinlal runs on the same day (34). Differences changed and thus SV lower during submaximal exercise
between CO hypoxia and hypobaric hypoxia could also be cornpared to the control experiment, which has also been
explained by the direct effect of CO in shifting the oxy- reported earlier by Klausen et al. (22) and Asrnussen and
hemoglobin dissociation curve to the left (30) and in- Chiodi (1). However, these findings are in contrast to the
hibiting oxidative enzymes (23). increased Q and unchanged SV reported by Vogel et al.
The lower stroke volume and thus reduced cardiac (35), who studied their subjects both with and without CO
output during the hypoxia experiments might be explained on the sarne day. By use of this protocol maximal exercise
by rnyocardial ischemia, which could be manifest as ST may have preceded so me submaximal exercise, thus influ-
depression on the ECG and/or lower pressure-rate product. encing the SV-HR relationship as pointed out by Hartley
However, analyses of the ECG’s revealed no evidence of et al. (11). This variation in experimental procedures
ischenlia during the hypoxia experiments and most other might explain the difference between the findings of Vogel
reports on the influence of hypoxia 011 circulation do not et al. and the results presented in the present study.
mention any ECG changes during inaxirnal exercise (5). The lactate concentration during submaximal exercise
The product of HR X MBP correlates well to myocardial was lower in the hyperoxia experiments compared to the
oxygen uptake (2 1). MBP was unchanged in the hypoxia control. This finding, which is in agreement with the report
experiment compared to control, but inax HR was signifi- by Fagraeus et al. (lo), may indicate a higher aerobic
cantly lower in the five subjects with HbCO levels higher energy yield, particularly during the beginning of exercise,
than 13 70. Furthermore, an earlier study from this labora- resulting in a lower 02 deficit.
tory (8) showed a significant difference in max HK between On subrnaxinlal work loads in the hypoxia experiment,
normoxia and CO-induced hypoxia (HbCO levels about when CaOz was reduced but Paoa remained normal, the
20 %), both during treadmill and bicycle maximal exer- pulmonary ventilation was unchanged compared to control.
cises, thus suggesting that higher CO levels exert a negative However, in acute low atmospheric hypoxia (33), when the
chronotropic effect on the heart which might be specific for C%~ and Pa9, are reduced, the VE is increased in com-
this form of hypoxia. In experiments with an acute expo- parison to values obtained under normal conditions. This
sure to a low atmospheric 0, pressure Q,,,,, and rnax HR finding agrees with earlier reports on the chemoreceptor
have been reported to be unchanged (12, 33). response to hypoxia ( 15).
In the hyperoxia experiment Q,,,,, and inax HR were Table 3 is a surnrnary of some cardiorespiratory func-
unchanged compared to control, but the MBP was signifi- tions, and their response to variations in arterial oxygen
cantly higher, giving a higher product of HR X MBP, content induced by different experimental procedures.
indicating a higher nlyocardial oxygen uptake. As discussed above the VoZ l1l&X shows a high correlation
The findings in this study as well as others (9, 10, 16,
18, 25-27, 36) suggest that the working muscle can utilize
“extra” oxygen during inaxirnal exercise. This is in con- TABLE 3. Some cardiores$Gatory functions studied during
trast to other studies (19, 29) that suggest that the main moderate
. I (SO-755% .of J?o2I ,,.J,l’“‘ submaximal (SM), and
/ 1 I\ .
limitation in the oxygen transport system is the capacity of maxzmal (Al) exerczse under dzJerent exper . imental conditions
-___
the oxidative enzvme chain in the skeletal muscles. Most - I ii02 QEBTPS HR 0
likely the Voz IllitX,‘*increased by hyperoxia, is utilized by the 1?ao2 Zao2 ---- ______
6
working muscles since there was an improvement in physical I;: SM nf snt SM SM
PI
performance. In the hyperoxia experiment the Vo2 nlaX was --
increased about 0.5 l/ min above control value. But where CO hypoxia 0 0 - 0 +
(this study &
in the working muscles was this extra 02 consumed? During
8)
normal conditions with “normal” values of Paoa and Caoz Low Pas hypoxia - 0 + +
slow-twitch muscle fibers, which are richer in rnyoglobin (33)
Acute anemia 0 0 0 +
and perhaps also grouped more closely around the capil- (7 & t>
laries than fast-twitch muscle fibers, probably consume High Po2 hy- 0 0 - -
most of the available oxygen during maximal exercise. But peroxia (this
study)
when Pa,, and Caoz are increased, it is possible that the Acute poly- 0 0 -
slow-twitch muscle fibers increase their oxidative energy cytemia (7 &
yield to a rate above that during normal conditions, or t>

perhaps there is more O2 available for the fast-twitch muscle + = S.gnificantincrease.

1 , - significant decrease; 0 unchanged values in the differ-
fibers. The question cannot be answered on the basis of the ent experimental situations compared to control. * SV unchanged during high
submaximal and decreased during low submaximal work. t Ekblom, B., G. Wil-
present results. It is of note also that the calculated rnixed son, and P.-O. Astrand. Central circulation during exercise after blood loss and
venous oxygen content at maximal running was somewhat after reinfusion. Submitted for publication.
ARTERIAL OXYGEN CONTENT, CIRCULATION, AND PHYSICAL PERFORMANCE 75

to the Caoz, regardless of the way the oxygen content is The authors thank Dr. Alf Holmgren, Head of the Laboratory of
modified. The ventilatory response in the different situa- Clinical Physiology, Thoracic Clinic, Stockholm, for his help in ana-
lyzing the blood samples for HbCO.
tions is also explainable by the effect of changes in PaO, on This study was supported by research grants from the Research
chemoreceptor activity. Council of the Swedish Sports Federation.
Changes in circulatory parameters including cardiac R. Huot was on leave from 1’Institute de Cardiologie de Montreal
and supported by a Fellowship from the Samuel McLaughlin Founda-
output do not exactly parallel alterations in Paoz and Caoz. tion.
It seems therefore that the regulatory mechanisms for ciru- E. M. Stein was on leave from and supported by Dept. of Medicine,
latory changes are more complex and not elucidated in Mount Sinai School of Medicine of the City University of New York.

this study. Received for publication 12 April 1974.

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