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Influence of body temperature on the development
of fatigue during prolonged exercise in the heat
JOSE
´GONZA
´LEZ-ALONSO, CHRISTINA TELLER, SIGNE L. ANDERSEN,
FRANK B. JENSEN, TINO HYLDIG, AND BODIL NIELSEN
Human Physiology Department, August Krogh Institute,
University of Copenhagen, DK-2100 Copenhagen, Denmark
Gonza´lez-Alonso, Jose´, Christina Teller, Signe L.
Andersen, Frank B. Jensen, Tino Hyldig, and Bodil
Nielsen. Influence of body temperature on the development
of fatigue during prolonged exercise in the heat. J. Appl.
Physiol. 86(3): 1032–1039, 1999.—We investigated whether
fatigue during prolonged exercise in uncompensable hot
environmentsoccurred atthe samecritical levelof hyperther-
mia when the initial value and the rate of increase in body
temperature are altered. To examine the effect of initial body
temperature [esophageal temperature (Tes)⫽35.9 ⫾0.2,
37.4 ⫾0.1, or 38.2 ⫾0.1 (SE) °C induced by 30 min of water
immersion], seven cyclists (maximal O2uptake ⫽5.1 ⫾0.1
l/min) performed three randomly assigned bouts of cycle
ergometer exercise (60% maximal O2uptake) in the heat
(40°C) until volitional exhaustion. To determine the influence
of rate of heat storage (0.10 vs. 0.05°C/min induced by a
water-perfusedjacket), fourcyclists performedtwo additional
exercise bouts, starting with Tes of 37.0°C. Despite different
initialtemperatures, allsubjects fatiguedat anidentical level
of hyperthermia (Tes ⫽40.1–40.2°C, muscle temperature ⫽
40.7–40.9°C,skin temperature ⫽37.0–37.2°C)andcardiovas-
cular strain (heart rate ⫽196–198 beats/min, cardiac output ⫽
19.9–20.8 l/min). Time to exhaustion was inversely related to
the initial body temperature: 63 ⫾3, 46 ⫾3, and 28 ⫾2min
with initial Tes of ⬃36, 37, and 38°C, respectively (all P⬍
0.05). Similarly, with different rates of heat storage, all
subjects reached exhaustion at similar Tes and muscle tem-
perature (40.1–40.3 and 40.7–40.9°C, respectively), but with
significantly different skin temperature (38.4 ⫾0.4 vs. 35.6 ⫾
0.2°C during high vs. low rate of heat storage, respectively,
P⬍0.05). Time to exhaustion was significantly shorter at the
high than at the lower rate of heat storage (31 ⫾4 vs. 56 ⫾11
min, respectively, P⬍0.05). Increases in heart rate and
reductions in stroke volume paralleled the rise in core
temperature(36–40°C), withskin bloodflowplateauing atTes
of ⬃38°C. These results demonstrate that high internal body
temperature per se causes fatigue in trained subjects during
prolonged exercise in uncompensable hot environments. Fur-
thermore, time to exhaustion in hot environments is in-
versely related to the initial temperature and directly related
to the rate of heat storage.
hyperthermia; skin blood flow; heart rate; stroke volume
IT IS WELL DOCUMENTED that endurance can be impaired
in hot compared with temperate climates (10, 12, 28)
and that time to exhaustion is influenced by alterations
of the initial body temperature (1, 22, 32, 39). The
attainment of a critically high level of body tempera-
ture has been proposed as the main factor limiting
endurance performance in hot environments (7, 28).
The observation that trained subjects working at 60%
of peak O2uptake (V
˙O2peak) in the heat [40°C, 10%
relative humidity (RH)] for 9–12 consecutive days
improved exercise performance from 48 to 80 min but
fatigued at a core temperature of 39.7°C appears to
support this notion (28). This large improvement in
exercise time to fatigue, however, was drastically re-
duced to 7 min when subjects exercised in a humid hot
environment, yet fatigue still coincided with a core
temperature of ⬃40°C (30). In the same light, Mac-
Dougal et al. (24) previously showed that subjects
always became exhausted at a rectal temperature of
39.4°C, even though the rate of rise had been varied
markedly with a water-perfused suit. More recently,
Fuller et al. (11) found that rats exercising in a hot
environment fatigued at the same abdominal and brain
temperature (⬃40°C) after preexercise body tempera-
ture was altered.
In opposition to the hypothesis of a critically high
body temperature, there are reports indicating that
some untrained subjects fatigue during light exercise
in uncompensable environments with body tempera-
tures of ⬃38°C (23, 26, 38). In untrained subjects, core
temperature at exhaustion from heat strain has been
clearly shown to occur over a range of 38–40°C (23, 26,
38) and to be independent of exercise intensity (26). It
has also been shown that, regardless of hydration or
acclimation status, subjects with high aerobic fitness
perform longer in uncompensable hot environments
and tolerate higher levels of hyperthermia than do
subjects with lower aerobic fitness levels (7). Therefore,
it appears that high body temperature might be the
mainfactorleading tofatigue in theheat in trainedand
in some, but not all, untrained subjects.
Although previous human studies have emphasized
the importance of core temperature, little is known
about exercising muscle temperature at exhaustion.
High muscle temperature might induce structural and
functional alterations in proteins involved in 1) electro-
lyte distributions across the sarcolemma, 2) calcium
release and reuptake by the sarcoplasmic reticulum, 3)
actin-myosin interactions, and 4) mitochondrial respi-
ration, which might potentially contribute to fatigue
(19). However, no previous study has systematically
manipulated the initial value and the rate of rise of
body temperature to determine whether fatigue in hot
environments is related to critically high core and/or
muscle temperatures.
It is also well established that heat stress reduces
stroke volume (SV) and increases heart rate during
The costs of publication of this article were defrayed in part by the
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8750-7587/99 $5.00 Copyright r1999 the American Physiological Society1032 http://www.jap.org
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moderately intense exercise to the extent to which
cardiac output might be compromised (35). In a classic
study, Rowell et al. (35) showed a significantly lower
cardiac output (⬃1.0 l/min), central blood volume, and
SV during exercise in a 43°C than in a 26°C environ-
ment at 63–73% V
˙O2peak. This reduced cardiac output
was due to the larger reductions in SV compared with
the parallel increases in heart rate. In a follow-up
study, Rowell et al. (36) found that alterations in
central blood volume, central venous pressure, SV, and
heart rate with heat stress could be restored by perfus-
ing a suit in contact with skin with cold water. In these
previous studies, however, skin blood flow was not
measured. Thus the contribution of higher skin perfu-
sion to SV reductions in conditions of widely different
body temperature remains unknown.
Therefore, the main aim of this study was to investi-
gate whether fatigue in trained athletes occurred at the
same critical level of core and muscle temperature,
despite differences in starting internal temperature
and its rate of rise. Asecondary aim was to determine
the effect of increased body temperature on heart rate,
SV, and skin blood flow under conditions of rather
different initial body temperatures. We hypothesized
that a similar critical level of internal body tempera-
ture would cause fatigue in trained athletes in uncom-
pensable hot environments. Furthermore, we hypoth-
esized that reductions in SV with heat stress are also
influenced by factors other than elevations in skin
blood flow. This hypothesis is based on previous obser-
vations showing that SV declines significantly with
core hyperthermia alone and combined hyperthermia
and hypovolemia when skin blood flow plateaus or
declines during prolonged exercise in the heat (13, 15,
16, 25).
METHODS
General Design
To accomplish these purposes, two different studies were
performed. To identify the effect of different initial body
temperature, one study was performed in the heat after core
temperature had been manipulated to three different levels
(⬃36,37, and38°C) byhaving subjects restin awater tankfor
30 min. Another study examined the influence of the rate of
increase in body temperature (0.05 vs. 0.10°C/min) on heat
exhaustion during prolonged exercise by having subjects
wear a water-perfused jacket.
Subjects
Age, body weight, height, maximal heart rate, and maxi-
mal O2uptake (V
˙O2max) of the seven healthy endurance-
trained men participating in these studies were 28 ⫾3yr,
77.9 ⫾6.4 kg, 187 ⫾6 cm, 200 ⫾9 beats/min, and 5.13 ⫾0.30
l/min, respectively. The subjects were fully informed of any
risks and discomforts associated with the experiments before
givingtheir informedconsent toparticipate. Thestudies were
approved by the Ethics Committee of Copenhagen and Fred-
eriksberg communities. Before performing the experimental
trials,subjects werefamiliarized withthe experimentalsetup
by cycling in a thermoneutral environment (20°C) for ⱖ90
min. Most of the subjects had participated in experiments
involving endurance performance in hot environments before
undergoing these experiments.
Experimental Design
In the study of the initial body temperature, subjects
performed three bouts of cycle ergometer exercise (model 829
E, Monark; 228 ⫾6W,88⫾1 rpm, 60% V
˙O2max)inan
uncompensable hot environment (40°C, 19% RH; Ereq/Emax
⬃1.2, where Ereq is evaporation required for heat balance and
Emax ismaximal evaporationcapacity) untilvolitionalexhaus-
tion. The following criteria were used to define volitional
fatigue in the present studies: 1) near or maximal values of
perceived exertion, 2) near or maximal heart rate, and 3)
inability to maintain a cadence of ⬃50 rpm. Trials were
randomly assigned and counterbalanced across subjects. Be-
fore exercise, resting body temperatures were manipulated
byimmersing subjectsin waterat 17,36, and40°Cfor 30min.
The conditions were as follows: 1) precooling (C) to an
esophageal temperature (Tes) of 35.9 ⫾0.2°C, a muscle
temperature (Tm) of 34.3 ⫾0.3°C, and an average skin
temperature (Tsk) of 29.5 ⫾0.3°C, 2) control (Con) with Tes of
37.4 ⫾0.1°C, Tmof 37.3 ⫾0.1°C, and Tsk of 34.2 ⫾0.1°C, and
3) preheating (H) to Tes of 38.2 ⫾0.1°C, Tmof 38.4 ⫾0.1°C,
and Tsk of 35.9 ⫾0.1°C (Figs. 1 and 2).
On the day before the experimental testing, the subjects
adopted the same diet, exercise bout (i.e., ⬍1hoflow-
intensity cycling), and fluid intake to standardize the hydra-
tion status. The subjects reported to the laboratory ⬃1h
before the experiment, after ingestion of a light breakfast and
200–300 ml of fluid. On arrival, nude body weight was
recorded. Thereafter, the esophageal probe was inserted
through the nasal passage, and the instruments used to
measureforearm bloodflow,skinblood flow,andskin tempera-
ture were attached to the skin. Thereafter, baseline values of
skin blood flow were obtained while subjects sat for 5–10 min
in a standardized position in the heat. The subjects then
restedfor 30min whileimmersed ina watertank. Thereafter,
subjects toweled dry and walked to the climatic chamber. The
transition period from the time the subjects emerged from the
water tank to the start of exercise was 8–12 min, with the
shortest time occurring during the preheating trial. Tmwas
measured immediately before and after exercise.
During exercise, heart rate, Tes, Tsk, and skin blood flow
were recorded continuously. O2uptake (V
˙O2), cardiac output
(CO2rebreathing), and forearm blood flow were measured
during a 10-min period starting at 3 min of exercise and
before exhaustion (when Tes was ⬃39.5°C). Forearm blood
flow was also measured during the 20- to 25-min period of C
and Con. Blood samples by finger prick were also obtained
before and immediately after exercise for later analysis of
blood glucose and lactate. Nude body weight was recorded
immediately after sweat was wiped off.A rating of perceived
exertion (RPE) was obtained at 10 min and at exhaustion (2).
Subjects received similar encouragement during each of the
trials.
The same control of previous exercise, nutrition, and
hydration status was applied in the study of the rate of heat
storage. On the subjects’ arrival at the laboratory, their nude
body weight was recorded. Skin and esophageal thermo-
couples were then attached to the skin or inserted through
the nasal passage, respectively. Thereafter, subjects rested
for 30 min in the supine position to ensure a similar initial
body temperature before exercise.
In this follow-up study, subjects performed two randomly
assignedbouts ofcycle ergometerexercise(258 ⫾20W,87⫾2
rpm, 66 ⫾3% V
˙O2max) in the heat (41°C, 17% RH) until
volitional fatigue. During exercise the rate of heat storage
1033HYPERTHERMIA AND FATIGUE
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was manipulated by changing the water temperature perfus-
ing the jacket in contact with the skin of the trunk and
forearms (42 vs. 19°C, i.e., high vs. low rate of heat storage).
However, in this study the initial Tes and Tmwere similar in
both trials: 36.9–37.1 ⫾0.1 and 36.3–36.5 ⫾0.2°C, respec-
tively. During exercise, heart rate was recorded continuously.
An RPE was obtained at 10 min and at exhaustion.
V
˙O2and Cardiac Output
PulmonaryV
˙O2wasmeasured on-linewith ametabolic cart
(model CPX/D, Medgraphics, St. Paul, MN). Cardiac output
was measured in triplicate using the CPX/D computerized
version of the CO2-rebreathing technique of Collier (8) and
corrected for differences between end-tidal and arterial PCO2
(21). Under similar exercise conditions, we previously ob-
served a tight temporal correlation between end-tidal and
arterial PCO2as well as between the estimated mixed venous
PCO2and femoral venous PCO2(r⫽0.85–0.91, P⫽0.0001)
(13). Heart rate was recorded with a PE 3000 Sport Tester
(Polar Electro).
Forearm Blood Flow and Skin Blood Flow
Forearm blood flow was measured using venous occlusion
plethysmography with a mercury-in-Silastic strain gauge
(40), while the wrist of the left forearm rested in a sling. The
hand was elevated ⬃15 cm above the heart level, and the
forearm was tilted 40° from the horizontal axis. Forearm
blood flow values represent the average of 8–10 single
measurements. Skin blood flow was measured using a laser-
Doppler flowmeter (model PF2B, Perimed, Stockolm, Swe-
Fig. 1. Esophageal temperature (A), mean skin temperature (B),
heart rate (C), and skin blood flow (D) during exercise in heat (40°C,
17% relative humidity) during precooling, control, and preheating
trials. Skin blood flow is referenced to resting baseline values
obtained on arrival at the laboratory (0.2–1.2 V; n⫽4). Values are
means ⫾SE for 7 subjects. *Significantly different from control,
P⬍0.05.
Fig. 2. Heart rate (A), cardiac output (B), stroke volume (C), skin
blood flow (D), and forearm blood flow (E) plotted against core
temperature during precooling, control, and preheating trials. Values
are means ⫾SE for 6 subjects.
1034 HYPERTHERMIA AND FATIGUE
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den). The laser-Doppler probe was placed on the left forearm
on the dorsal side, separated ⬃2 cm from the plethysmo-
graphic strain gauge. Skin blood flow and forearm blood flow
were recorded at 100 Hz with use of a MacLab/8s (AD
Instruments) data-acquisition system.
Core, Skin, and Muscle Temperature
Tes was measured with a thermocouple (model MOV-A,
Ellab) inserted through the nasal passage a distance equal to
one-fourth of the subject’s standing height. Tsk was calculated
from the skin temperatures (model A-H3, Ellab) measured at
six sites (i.e., upper arm, forearm, chest, back, thigh, and calf)
byusing theweighting methodof Hardyand DuBois(18). The
esophageal and skin thermocouples were connected to a
recorder (CTF 90008 precision thermometer, Ellab) inter-
faced to an IBM-AT computer. Tmwas measured in the vastus
lateraliswith aneedle probe(model MKA-A,Ellab) inserted3
cm into the muscle.
Percent Dehydration
Percent dehydration was estimated from the differences in
body weight after exercise compared with the preexercise
body weight, with correction for body weight loss due to the
exchange of O2and CO2(33). Nude body weight was deter-
mined on a platform scale (model 1-10, Ohaus) with an
accuracy of ⫾20 g.
Statistical Analysis
A two-way (trial-by-time) repeated-measure ANOVA was
performed to test significance between and within treat-
ments. After a significant Ftest, pairwise differences were
identified using Tukey’s honestly significant difference post
hocprocedure. Whenappropriate, significantdifferenceswere
also identified using Student’s paired t-tests. The significance
level was set at P⬍0.05. Values are means ⫾SE unless
otherwise indicated.
RESULTS
Influence of Different Initial Body Temperatures
Body temperatures and performance time. Despite
different initial temperatures, all subjects fatigued at
an identical level of hyperthermia: Tes of 40.1 ⫾0.1,
40.2 ⫾0.1, and 40.1 ⫾0.1°C, Tmof 40.7 ⫾0.1, 40.8 ⫾
0.1, and 40.9 ⫾0.1°C, and Tsk of 37.2 ⫾0.2, 37.2 ⫾0.1,
and 37.0 ⫾0.1°C during C, Con, and H, respectively
(Fig. 1, Table 1). In three trials the between-subjects
difference in Tes at exhaustion was 0.1–0.5°C (Table 1).
The rate of heat storage during exercise was the same
in the three conditions. Therefore, time to exhaustion
was inversely related to starting body temperatures:
63 ⫾3, 46 ⫾3, and 28 ⫾2 min in C, Con, and H,
respectively (all P⬍0.05).
Hydration status. Hydration was similar before exer-
cise, as indicated by similar body weights: 76.6 ⫾6.6,
77.1 ⫾5.8, and 76.4 ⫾6.1 (SD) kg before C, Con, and H,
respectively [not significant (NS)]. Furthermore, simi-
lar body weight losses occurred from the start of water
immersion to the end of exercise: 2.0 ⫾0.3, 1.9 ⫾0.3,
and 2.1 ⫾0.2 kg during C, Con, and H, respectively
(P⫽NS).Therefore,the levelof dehydration atexhaus-
tion was also similar in each trial: 2.6 ⫾0.4, 2.4 ⫾0.3,
and 2.8 ⫾0.3% body wt loss during C, Con, and H,
respectively (P⫽NS).
Cardiovascular responses. After 10 min of exercise,
V
˙O2was similar during all conditions (range 3.05 ⫾
0.05 to 3.11 ⫾0.13 l/min), despite the 2.4°C difference
in Tes between C and H. Thereafter, V
˙O2tended to
increase over time. In contrast, cardiac output, SV, and
heart rate were graded in proportion to the magnitude
of hyperthermia. Cardiac output was 22.5 ⫾1.1, 21.8 ⫾
0.8, and 20.3 ⫾0.5 l/min, SV was 152 ⫾7, 126 ⫾6, and
109⫾4ml/beat (allP⬍0.05), andheartrate was140 ⫾
5, 166 ⫾5, and 182 ⫾4 beats/min (all P⬍0.05) with Tes
of 36.5, 38.3, and 38.9°C for C, Con, and H, respectively
(Fig. 2). Cardiac output was significantly (P⬍0.05)
lower during H than during C (2.2 ⫾0.9 l/min), yet the
differences between these two trials and Con (0.7 ⫾0.5
and 1.2 ⫾0.8 l/min) did not reach statistical signifi-
cance. Concurrently, arterial mixed-venous O2differ-
ence was 13.9 ⫾0.05, 14.0 ⫾0.04, and 15.2 ⫾0.07
ml/100 ml during C, Con, and H, respectively. However,
these large differences in cardiovascular response at 10
min of exercise were markedly reduced at exhaustion
(Fig. 2). At exhaustion in C, Con, and H, cardiac output
was 20.8 ⫾0.7, 20.2 ⫾0.6, and 19.9 ⫾0.4 l/min; SV was
106 ⫾5, 104 ⫾4, and 103 ⫾4 ml/beat; heart rate was
198 ⫾4, 197 ⫾4, and 196 ⫾4 beats/min; and arterial
mixed-venous O2difference was 15.1 ⫾0.3, 15.3 ⫾0.6,
and 15.8 ⫾0.6 ml/100 ml, respectively (all P⫽NS).
Heart rate at point of fatigue was 98–99% of maximal
heart rate.
Table 1. Individual variability and reproducibility of Tes,T
m, and Tsk at exhaustion
in the study of different initial body temperatures
Subject
Tes TmTsk
Precooling Control Preheating Precooling Control Preheating Precooling Control Preheating
LH 40.3 40.2 39.9 40.4 40.6 40.4 37.3 37.0 36.9
HH 40.0 40.2 40.2 40.2 40.9 41.2 37.3 37.5 37.0
TJ 39.7 40.2 40.3 40.9 41.2 41.2 37.5 37.0 37.1
PM 39.9 40.1 39.9 40.6 40.7 40.5 37.0 37.5 36.9
CJ 40.3 40.3 40.2 41.2 40.7 40.8 37.2 36.6 36.7
JT 40.0 40.4 40.3 40.8 41.0 41.0 36.4 37.4 37.2
HF 40.3 40.2 40.2 40.7 40.8 41.0 37.6 37.3 37.0
Mean⫾SE 40.1⫾0.1 40.2⫾0.1 40.1⫾0.1 40.7⫾0.1 40.8⫾0.1 40.9⫾0.1 37.2⫾0.2 37.2⫾0.1 37.0⫾0.1
Tes, esophageal temperature; Tm, vastus lateralis muscle temperature; Tsk , mean skin temperature.
1035HYPERTHERMIA AND FATIGUE
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Forearm and skin blood flow. During the first 3–8
min of exercise, forearm blood flow was significantly
lower during C than during Con and H: 2.0 ⫾0.2 vs.
8.6 ⫾1.0 and 11.5 ⫾1.4 ml·100 ml⫺1·min⫺1, respec-
tively (P⬍0.05; Fig. 2). At exhaustion, forearm blood
flow was lower during H than during Con and C: 9.6 ⫾
1.0 vs. 12.1–12.2 ⫾1.2 ml·100 ml⫺1·min⫺1, respec-
tively (P⬍0.05).
Baseline resting skin blood flow values (before water
immersion) were 0.2–1.2 V. During exercise, skin blood
flow in Con increased somewhat during the first 10 min
and reached a plateau thereafter (Fig. 1). During H,
skin blood flow was at plateau levels from the initial
minuteofexercise. Incontrast, skin bloodflow duringC
increased gradually after the first 4 min of exercise and
reached a plateau level after 20 min of exercise (Fig. 1).
In all trials, skin blood flow reached a plateau level
after Tes had increased above ⬃38°C (Fig. 2).
Blood lactate and blood glucose. At exhaustion, nei-
ther blood lactate nor blood glucose was different
between trials. Blood lactate ranged from 1.6 ⫾0.1 to
2.2 ⫾0.2 mM, whereas blood glucose was maintained
at euglycemic levels in all conditions: 6.3 ⫾0.1 to 6.7 ⫾
0.4 mM.
RPE. At 10 min, RPE was significantly lower during
C than during H: 10.6 ⫾0.9 vs. 13.7 ⫾0.7 units,
respectively (P⬍0.05). RPE increased significantly
over time in all trials. However, RPE at exhaustion was
equally high in all trials: 18.5 ⫾0.2 to 18.6 ⫾0.3 units
(P⫽NS).
Influence of Different Rates of Heat Storage
Bodytemperatures andperformancetime. Withdiffer-
entrateof heatstorage, allsubjectsreached exhaustion
at similar Tes and Tm(40.3 ⫾0.3 vs. 40.1 ⫾0.3°C for Tes
and 40.9 ⫾0.3 vs. 40.7 ⫾0.3°C for Tmduring high vs.
lower rate of heat storage, respectively), but with
significantly (P⬍0.05) different Tsk (38.4 ⫾0.4 vs.
35.6 ⫾0.2°C for Tsk during high vs. lower rate of heat
storage, respectively; Fig. 3, Table 2). Reflecting the
experimental manipulation, this ⬃3°C difference in Tsk
was attributable only to the effect of the water-perfused
jacket on skin from the trunk and forearms. In both
trials the difference in Tes at exhaustion in each of the
subjects ranged from 0.0 to 0.3°C (Table 2). Time to
exhaustion was significantly shorter during the high
than during the lower rate of heat storage: 31 ⫾4 vs.
56 ⫾11 min, respectively (P⬍0.05). The large SE
during the lower rate of heat storage trial was due to
differences in relative intensity between subjects. The
two subjects who exercised at 71% V
˙O2max improved
time to exhaustion by 8 and 9 min, whereas the two
subjects who worked at 61% V
˙O2max improved much
more (34 and 48 min). Heart rate response paralleled
the rise in core temperature, being significantly higher
during the high heat storage trial, except at exhaus-
tion, when between-trial differences were not signifi-
cant: 187 ⫾7to189⫾7 beats/min or 95–96% of
maximal heart rate (Fig. 3C).
Hydration status. Hydration was similar before exer-
cise, as indicated by similar body weights: 78.3 ⫾4.8
and 78.4 ⫾4.6 (SD) kg during the high and lower rate
trials, respectively (P⫽NS). Body weight losses during
exercise were higher during the lower rate than during
the high rate of heat storage: 1.7 ⫾0.3 vs. 1.1 ⫾0.1 kg
(P⬍0.05). Therefore, the levels of dehydration were
higher during the lower rate than during the high rate
of heat storage: 2.1 ⫾0.4 vs. 1.5 ⫾0.1% body wt loss,
respectively (P⬍0.05).
RPE. At 10 min of exercise, RPE was lower during
thelower rate thanduring thehigh rateof heat storage:
10.8 ⫾0.6 vs. 13.0 ⫾0.7 units (P⬍0.05). At exhaus-
tion, RPE was equally high in both trials: 19.5 ⫾0.5
and 19.8 ⫾0.3 units (P⫽NS).
DISCUSSION
Themainaim ofthis study wasto determinewhether
trained subjects fatigued in an uncompensable hot
environment at the same core and muscle tempera-
tures, regardless of the initial value and the rate of rise
of body temperature. We found that exhaustion during
moderate exercise occurred at the same high level of
Fig. 3. Esophageal temperature (A), mean skin temperature (B), and
heart rate (C) during exercise in heat (40°C, 17% relative humidity)
while subjects wore a water-perfused jacket to alter rate of heat
storage. Values are means ⫾SE for 4 subjects. *Significantly
different from lower rate of heat storage trial, P⬍0.05.
1036 HYPERTHERMIA AND FATIGUE
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internal body temperature and RPE when the initial
value or the rate of increase in body temperature was
altered. We also observed that increases in heart rate
andreductions inSV paralleledtheriseincore tempera-
ture from 36 to 40°C, with skin blood flow plateauing
when core temperature reached ⬃38°C. This suggests
that increases in heart rate might contribute to reduc-
tions in SV with heat stress.
High Temperature and Fatigue
The main finding of these studies was that fatigue
during exercise in the heat was related to high internal
body temperature. This is based on the observation
that, in both studies, trained subjects fatigued at
similar Tes and Tm(40.1–40.3 and 40.7–40.9°C, respec-
tively), even though Tsk was 2–3°C lower during the
lower rate of heat storage trial. The between-trial
variability in core temperature and Tmat exhaustion
was very small in both studies: 0.3 ⫾0.1°C (Tables 1
and 2). Time to exhaustion ranged from 28 to 63 min,
being shortest with highest initial body temperature
and higher rate of heat storage. Fatigue in the present
heat stress condition is clearly related to high body
temperature, because these trained cyclists could cycle
to exhaustion at the same intensity in the heat for ⬎2h
when core temperature rose at a slower rate to 39.7 ⫾
0.2°C (13).
The present findings confirm previous observations
from this laboratory indicating that trained subjects
fatigued with core temperatures of ⬃40°C when work-
ing at 50–60% V
˙O2peak in the heat (40°C, 10% RH) for
9–12 consecutive days (28, 30). Exercise time to fatigue
increasedfrom48 ⫾2to80⫾3 min fromthe first tothe
lastacclimation day,owing inpartto alower initialcore
temperature with heat acclimation (28). This large
improvement in exercise time to fatigue was drastically
reduced to 5–10 min when the subjects exercised in a
humid environment but still coincided with a core
temperature of 39.9 ⫾0.1°C (30). Interestingly, fatigue
in all these previous studies was not associated with
any reductions in cardiac output, exercising leg blood
flow, leg substrate availability and utilization, or accu-
mulation of lactate, K⫹, or other proposed ‘‘fatigue’’
substances (28–30). Furthermore, muscle glycogen lev-
els at the point of fatigue have been shown to be quite
high in these conditions (⬎300 mmol/kg dry wt) (10, 13,
29). Presently, we also observed low concentrations of
blood lactate and euglycemic levels of blood glucose as
wellassimilar heartrateand cardiacoutput at exhaus-
tion. Taken together, it appears that hyperthermia,
rather than altered circulation and metabolism, is the
mainfactorcausing fatigueinthe presentconditions. It
is recognized, however, that these and other factors
such as dehydration, training status, heat acclimation,
and environmental conditions, as well as duration and
intensity of exercise, might interact and alter the
tolerance to hyperthermia (8, 13, 23, 26, 29, 38).
Evidence in humans and animals also supports the
notion that fatigue in hot environments appears to
coincide with a critically high internal body tempera-
ture (6, 11, 12, 14, 17, 24). There are reports indicating
that some untrained subjects fatigued during exercise
inuncompensable hotenvironments withbody tempera-
tures of ⬃38°C (23, 26, 38). In untrained and moder-
ately fit subjects, core temperature at exhaustion from
heat strain during low-intensity exercise has been
shown to occur over a range of 38–40°C (23, 26, 38).
Differences in subjects’training status appear to be the
mainreasonfor thediscrepancyin thetolerance to heat
strain between the present and previous studies (23,
26, 38). In this light, it has been elegantly shown that
subjects with higher aerobic fitness perform longer and
tolerate higher levels of hyperthermia (39.2 vs. 38.8°C)
in uncompensable hot environments than their less fit
counterparts (7). Our present results extend previous
findings by examining high metabolic rates in highly
conditioned athletes. Furthermore, we presently deter-
mined the influence of active muscle temperature on
fatigue in hot environments.
The mechanism by which hyperthermia causes fa-
tigue is not well understood. We have presently ob-
served a similar muscle and core temperature at the
point of fatigue, despite a different upper body skin
temperature in the rate study. Under these conditions,
it is expected that hypothalamic and other internal
organ temperatures would also reach a similarly high
level at the point of fatigue (11). In this context, we
could speculate that fatigue mainly responded to sig-
nals originating in the active muscle, internal organs,
and/or central nervous system, secondary to the rise in
temperature. The detrimental effects of hyperthermia
on muscle function and metabolism are well docu-
mented (4, 9, 10). Furthermore, hyperthermia is known
to stimulate the release of endotoxins and heat shock
proteins from the internal organs, which might contrib-
ute to fatigue (see Ref. 17 for review). Alternatively,
hyperthermia might reduce the central drive for exer-
cise by influencing the motor control center in the brain
Table 2. Individual variability and reproducibility of Tes,T
m, and Tsk at exhaustion in the study
of different rate of increase in body temperature
Subject
Tes TmTsk
High rate Lower rate High rate Lower rate High rate Lower rate
JR 39.6 39.4 40.6 40.1 37.7 35.6
CJ 41.1 40.8 41.6 41.4 39.6 35.8
HF 40.3 40.1 40.7 40.8 38.3 35.9
PM 40.1 40.1 40.5 40.7 38.1 35.2
Mean⫾SE 40.3⫾0.3 40.1⫾0.3 40.9⫾0.3 40.7⫾0.3 38.4⫾0.4 35.6⫾0.2
1037HYPERTHERMIA AND FATIGUE
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(5, 28). Whether these factors interact or act indepen-
dently awaits further investigations. Irrespective of its
origin, however, it is clear that this mechanism acts to
protect humans and animals from reaching tissue
temperatures that jeopardize cell function.
Cardiovascular Responses to Exercise
Anotherinterestingobservation ofthestudy ofdiffer-
ent initial temperatures was that cardiac output was
2.2 ⫾0.9 l/min lower during preheating than during
the precooling trial at 10 min of exercise, yet whole
body V
˙O2was unaltered. Previous studies comparing
exercise in hot (36–44°C) vs. neutral environments and
exercise with hot vs. cold water perfusing a suit in
contact with the skin have shown cardiac output to be
increased (27, 29, 35), unchanged (27, 35), or reduced
(35). The present finding that the combined elevations
in Tsk,T
es (2.4–3.1°C), and skin blood flow (⬃8 ml·100
ml⫺1·min⫺1or 4-fold elevation) reduced cardiac output
during moderately intense exercise confirms previous
results of Rowell et al. (35) in untrained subjects. They
observed a significantly lower cardiac output (1.0–1.2
l/min), central blood volume (0.1–0.2 liter), and SV
(⬃20 ml) when subjects exercised in a 43°C than in a
26°C environment at 63–73% V
˙O2peak (34).
In the present study and the study of Rowell et al.
(35), the decrease in cardiac output with hyperthemia
is attributed to the larger decline in SV (Fig. 2). The
mechanism mediating this reduced SV with hyperther-
mia has not been directly elucidated. The prevailing
hypothesis is that reductions in SV with heat stress are
due to increased skin blood flow and volume (20, 34).
Rowell (34) speculated that increased skin blood flow
reduces SV by reducing ventricular filling as a result of
displacement of blood from the central circulation to
peripheral skin veins as core temperature increases.
Evidence showing that the lower SV, central venous
pressure, and central blood volume with whole body
heating are reversed by whole body cooling (36) ap-
pears to support this notion. However, this manipula-
tionaltersnot onlyskin blood flowand Tsk, butalso core
temperature, which have been shown to alter heart
rate and SV independently (16). An increase in Tes of
1°C has been shown to increase heart rate by 9 ⫾1
beats/min and reduce SV by 11 ⫾3 ml when skin blood
flow was the same (16). It seems, therefore, that the
mechanism mediating SV reductions with heat stress
is complex and might be influenced by several factors.
In the present study with markedly different heat
strain conditions at 10 min of exercise (Fig. 1), it seems
likely that central blood volume and right atrial pres-
sure were also significantly reduced in H compared
with C. An interesting observation was that skin blood
flow reached a plateau at Tes of ⬃38°C in all trials, in
agreement with early and recent reports (3, 13, 15, 25,
30). This indicates that the observed further reductions
in SV with core temperature above ⬃38°C (i.e., ⬃20 ml)
were clearly not associated with increased skin blood
flow (Fig. 2, C–E). This agrees with the observations
that most of the reductions in central blood volume and
right atrial pressure with heat stress occur early in
exercise (31, 35) and that right atrial pressure declines
onlyslightlyafter skinbloodflow hasreacheda plateau
level (31). As shown in Fig. 2A, increases in heart rate
from 130 beats/min to almost maximal levels (196–198
beats/min) were strongly correlated with increases in
core temperature (r2⫽0.98, P⫽0.001). Heart rate at a
given temperature was remarkably similar among tri-
als. Because heart rate is influenced by multiple fac-
tors, it is not clear from our experiment to what extent
this increase in heart rate responds to decreased SV
and reduced stretching of the heart (Frank-Starling
mechanism) and/or direct effect of warm blood on the
sinus node and neurohumoral stimuli (37). It seems
reasonable, however, to speculate that the increase in
heart rate at Tes ⬎38°C was largely related to increases
inbodytemperature. Thistheory suggests thatreduced
cardiac filling time (i.e., higher heart rate) might also
contribute to reductions in SV with hyperthermia,
particularly in conditions of reduced central venous
pressure and central blood volume. Another possibility
isthathigh cardiactemperature reducesSVby altering
cardiac contractility.
In conclusion, these results demonstrate that high
body temperature per se causes fatigue in trained
subjects during prolonged exercise in uncompensable
hot environments. Furthermore, time to exhaustion in
hot environments in trained subjects is inversely re-
lated to the initial level of body temperature and
directly related to the rate of heat storage. In addition,
marked elevations in body temperature (2–3°C) and
skin blood flow (4-fold) resulted in significant reduc-
tions in cardiac output due to the larger decline in SV,
yet whole body V
˙O2was unaltered. The observation
that increases in heart rate and reductions in SV
paralleled the rise in core temperature from 36 to 40°C,
while skin blood flow plateaus at Tes of ⬃38°C, supports
thecontentionthat increasesin heartratecontribute to
reductions in SV with heat stress.
The authors thank the subjects for their enthusiasm.
These studies were supported by grants from Team Danmark and
the European Commission. J. Gonza´lez-Alonso was supported by
Marie Curie Research Training Grant FMBICT950007.
Addressfor reprintrequests: J. Gonza´lez-Alonso,The Copenhagen
Muscle Research Center, Rigshospitalet, Section 7652, 20 Tagenvej,
DK-2200 Copenhagen N, Denmark.
Received 17 September 1998; accepted in final form 28 October 1998.
REFERENCES
1. Booth, J., F. Marino, and J. J. Ward. Improved running
performance in hot humid conditions following whole body
precooling. Med. Sci. Sports Exerc. 29: 943–949, 1997.
2. Borg, G. Simple rating methods for estimation of perceived
exertion. In: Physical Work and Effort, edited by G. Borg. New
York: Pergamon, 1975, p. 39–46.
3. Brengelmann, G. L., J. M. Johnson, L. Hermansen, and
L. B. Rowell. Altered control of skin blood flow during exercise
at high internal temperature. J. Appl. Physiol. 43: 790–794,
1977.
4. Brooks, G. A., K. J. Hittleman, J. A. Faulkner, and R. A.
Beyer. Temperature, skeletal muscle mitochondrial functions,
and oxygen debt. Am. J. Physiol. 220: 1053–1059, 1971.
5. Bru¨ ck, K., and H. Olschewski. Body temperature related
factors diminishing the drive to exercise. Can. J. Physiol. Phar-
macol. 65: 1274–1280, 1987.
1038 HYPERTHERMIA AND FATIGUE
Downloaded from www.physiology.org/journal/jappl (181.214.028.046) on June 16, 2019.
6. Caputa, M., G. Feistkorn, and C. Jessen. Effects of brain and
trunk temperatures on exercise performance in goats. Pflu¨gers
Arch. 406: 184–189, 1986.
7. Cheung, S. S., and T. M. McLellan. Heat acclimation, aerobic
fitness,and hydrationeffectson tolerance duringuncompensable
heat stress. J. Appl. Physiol. 84: 1731–1739, 1998.
8. Collier, C. R. Determination of mixed venous CO2tensions by
rebreathing. J. Appl. Physiol. 9: 25–29, 1956.
9. Febbraio, M. A., M. F. Carey, R. J. Snow, C. G. Stathis, and
M. Hargreaves. Influence of elevated muscle temperature on
metabolism during intense, dynamic exercise. Am. J. Physiol.
271 (Regulatory Integrative Comp. Physiol. 40): R1251–R1255,
1996.
10. Febbraio, M. A., R. J. Snow, C. G. Stathis, M. Hargreaves,
and M. F. Carey. Effect of heat stress on muscle energy
metabolism during exercise. J. Appl. Physiol. 77: 2827–2831,
1994.
11. Fuller, A., R. N. Carter, and D. Mitchell. Brain and abdominal
temperatures at fatigue in rats exercising in the heat. J. Appl.
Physiol. 84: 877–883, 1998.
12. Galloway, S. D. R., and R. J. Maughan. Effects of ambient
temperature on the capacity to perform prolonged exercise in
man. Med. Sci. Sports Exerc. 29: 1240–1249, 1997.
13. Gonza´ lez-Alonso, J., J.A. L. Calbet, and B. Nielsen. Muscle
blood flow is reduced with dehydration during prolonged exercise
in humans. J. Physiol. (Lond.) 513: 895–905, 1998.
14. Gonza´ lez-Alonso, J., J. A. L. Calbet, and B. Nielsen. Meta-
bolic alterations with dehydration-induced reductions in muscle
blood flow in humans (Abstract). Eur. Coll. Sport Sci. Meeting,
Copenhagen, Denmark, 1997, p. 492–493.
15. Gonza´ lez-Alonso, J., R. Mora-Rodrı´guez, P. R. Below, and
E. F. Coyle. Dehydration reduces cardiac output and increases
systemic and cutaneous vascular resistance during exercise. J.
Appl. Physiol. 79: 1487–1496, 1995.
16. Gonza´ lez-Alonso, J., R. Mora-Rodrı´guez, P. R. Below, and
E. F. Coyle. Dehydration markedly impairs cardiovascular
function in hyperthermic endurance athletes during exercise. J.
Appl. Physiol. 82: 1229–1236, 1997.
17. Hales, J. R. S., R. W. Hubbard, and S. L. Gaffin. Limitation of
heattolerance. In: HandbookofPhysiology.EnvironmentalPhysi-
ology. Bethesda, MD: Am. Physiol. Soc., 1996, sect. 4, vol. II,
chapt. 15, p. 285–355.
18. Hardy, J. D., and E. F. DuBois. The technique of measuring
radiation and convection. J. Nutr. 5: 461–475, 1938.
19. Hargreaves, M., and M. Febbraio. Limits to exercise perfor-
mance in the heat. Int. J. Sports Med. 19: S115–S116, 1998.
20. Johnson, J. M., and L. B. Rowell. Forearm skin and muscle
vascular responses to prolonged leg exercise in man. J. Appl.
Physiol. 39: 920–924, 1975.
21. Jones, N. L., D. G. Robertson, and J. W. Kane. Difference
between end-tidal and arterial PCO2in exercise. J. Appl. Physiol.
47: 954–960, 1979.
22. Kruk, B., H. Pekkarinen, M. Harri, and O. Hanninen.
Thermoregulatoryresponses toexerciseat lowambienttempera-
ture performed after precooling or preheating. Eur. J. Appl.
Physiol. 59: 416–420, 1990.
23. Latzka, W. A., M. N. Sawka, S. J. Montain, G. S. Skrinar,
R. A. Fielding, R. P. Matott, and K. B. Pandorf. Hyperhydra-
tion: tolerance and cardiovascular effects during uncompensable
exercise-heat stress. J. Appl. Physiol. 84: 1858–1864, 1998.
24. MacDougal, J. D., W. G. Reddan, C. R. Layton, and J. A.
Dempsey. Effects of metabolic hyperthermia on performance
during heavy prolonged exercise. J. Appl. Physiol. 36: 538–544,
1974.
25. Montain, S. L., and E. F. Coyle. Fluidingestion duringexercise
increases skin blood flow independent of blood volume. J. Appl.
Physiol. 73: 903–910, 1992.
26. Montain, S. L., M. N. Sawka, B. S. Cadarette, M. D. Quigley,
and J. M. McKay. Physiological tolerance to uncompensable
heat stress: effects of exercise intensity, protective clothing, and
climate. J. Appl. Physiol. 77: 216–222, 1994.
27. Nadel, E. R., E. Cafarelli, M. F. Roberts, and C. B. Wenger.
Circulatory regulation during exercise in different ambient tem-
peratures. J. Appl. Physiol. 46: 430–437, 1979.
28. Nielsen, B., J. R. S. Hales, S. Strange, N. J. Christensen, J.
Warberg, and B. Saltin. Human circulatory and thermoregula-
tory adaptations with heat acclimation and exercise in a hot, dry
environment. J. Physiol. (Lond.) 460: 467–485, 1993.
29. Nielsen, B., G. Savard, E. A. Ritcher, M. Hargreaves, and B.
Saltin. Muscle blood flow and metabolism during exercise and
heat stress. J. Appl. Physiol. 69: 1040–1046, 1990.
30. Nielsen, B., S. Strange, N. Christensen, J. Warberg, and B.
Saltin. Acute and adaptative responses to exercise in a warm,
humid environment. Pflu¨ gers Arch. 434: 49–56, 1997.
31. Nose, H., A. Takamata, G. W. Mack, Y. Oda, T. Kawabata, S.
Hashimoto, M. Hirose, E. Chihara, and T. Marimoto. Right
atrial pressure and forearm blood flow during prolonged exercise
in a hot environment. Pflu¨ gers Arch. 426: 177–182, 1994.
32. Olschewski,H., and K.Bru¨ck. Thermoregulatory,cardiovascu-
lar and muscular factors related to exercise after precooling. J.
Appl. Physiol. 64: 803–811, 1988.
33. Pugh, L. G. C., J. I. Corbett, and R. J. Johnson. Rectal
temperatures, weight losses, and sweating rate in marathon
running. J. Appl. Physiol. 23: 347–352, 1957.
34. Rowell, L. B. Human Circulation: Regulation During Physical
Stress. New York: Oxford University Press, 1986, p. 174–406.
35. Rowell, L. B., H. J. Bruce, R. D. Conn, and F. Kusumi.
Reductions in cardiac output, central blood volume, and stroke
volume with thermal stress in normal men during exercise. J.
Clin. Invest. 45: 1801–1816, 1966.
36. Rowell, L. B., J. A. Murray, G. L. Brengelmann, and K. K.
Kraning. Human cardiovascular adjustments to rapid changes
in skin temperature during exercise. Circ. Res. 24: 711–724,
1969.
37. Rubin, S. A. Core temperature regulation on heart rate during
exercise in humans. J. Appl. Physiol. 62: 1997–2002, 1987.
38. Sawka, M. N., A. J. Young, W.A. Latzka, P. D. Neufer, M. D.
Quicley, and K. B. Pandolf. Human tolerance to heat strain
during exercise: influence of hydration. J. Appl. Physiol. 73:
368–375, 1992.
39. Schmidt, V., and K. Bru¨ ck. Effect of a precooling maneuver on
bodytemperature andexerciseperformance. J.Appl.Physiol. 50:
772–778, 1981.
40. Whitney, R. J. The measurement of volume changes in human
limbs. J. Physiol. (Lond.) 121: 1–27, 1953.
1039HYPERTHERMIA AND FATIGUE
Downloaded from www.physiology.org/journal/jappl (181.214.028.046) on June 16, 2019.
