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Factors affecting the regulation of body temperature during exercise
.I. therm. Biol. Vol. 8. pp. 165 to 169. 1983
0306-4565/83/010165-05505.00;0 Copyright © 1983 Pergamon Press Ltd
Printed in Great Britain. All rights reserved
REVIEW FACTORS AFFECTING THE REGULATION OF BODY TEMPERATURE D U R I N G EXERCISE ETHAN R. NADEL John B. Pierce Foundation Laboratory and Departments of Epidemiology and Public Health and Physiology, Yale University School of Medicine, New Haven, CT 06519 U.S.A. Abstract--1. During exercise, the heat produced in the contracting muscles causes internal body temperature to rise until the heat-dissipation responses, increasingly driven by the rising temperature, provide for a new balance between heat-production and heat-loss rates. 2. The new elevated steady-state internal body temperature is not invariant, but can be affected by a number of factors, such as wetness of the skin or state of body hydration. 3. Progressive dehydration, such as occurs during prolonged exercise or exercise in the heat, results in relative hyperthermia caused by increased thresholds and decreased sensitivities of the heat-dissipation mechanisms. Independent manipulations of blood volume and osmolality reveal that these variables exert their effects on the thermoregulatory system by somewhat different means.
DURING exercise, heat is produced in the contracting muscles at a rate proportional to the exercise intensity. Fit individuals are able to sustain a rate of heat production in excess of 1200W (15 times the basal rate) for extended periods. Practically all of this heat is convected to the body core in the venous return of blood from the muscles, and most of this heat is rapidly dissipated to the environment by radiation, convection and/or evaporation. Without an efficient temperature regulatory system, involving elements that sense the increased body temperatures, elements that evaluate the body-temperature elevations and elements that provide for increased heat-transfer rates from core-to-skin and from skin-to-environment, heavy exercise or exercise in the heat would be limited to 10--15 min by excessive hyperthermia. It is now well known that M. Nielsen (1938) was the first to thoroughly describe the observation that internal body temperature increases during muscular exercise and eventually arrives at a new steady state that is roughly proportional to the absolute exercise intensity and independent of the ambient temperature (between 5 and 30°C, at least). Nielsen interpreted these data as indicating that the increase in internal temperature was a regulated one, caused by a new, higher body temperature set point during exercise. About a decade later Robinson (1949) published an extremely comprehensive review on the topic of physiological adjustments to heat and exercise. Robinson showed that the sweating rate during exercise could be described by a proportional control model. Sweating rate was found to be a linear function of internal body temperature; the average skin temperature was also found to affect sweating rate, although to a much lesser extent per degree change than internal temperature. Skin temperature changes served to adjust the internal temperature threshold for sweating. Robinson concluded that the "... rise in sweating apparently was a direct effect of internal temperature on the heat regulatory centers (sic.) and was possibly due also to stimulation of the centers
resulting from the increasing neuromuscular activity." In other words, Robinson appears to have claimed that the internal temperature increase was the primary drive for the sweating response and, further, although he had no evidence for such an effect, that sweating activity might be influenced by factors related to the exercise itself. With Robinson's model, since confirmed and expanded upon by others (e.g. Nadel et al., 1971), there is no need to postulate an altered "'set point" during exercise, and indeed, there is now an accumulated body of evidence against this concept (Nielsen & Nielsen, 1965; Cabanac et al., 1971; Stitt, 1979). The elevated internal temperature is a consequence of the temporary imbalance between the rates of heat production and heat dissipation. At the onset of exercise the body's rate of heat production suddenly is much greater than the rate of dissipation and the extra heat is stored, thereby causing internal body temperature to rise. The rise in internal temperature initiates increases in cutaneous blood flow and sweating rate and these activated heat-dissipation responses attenuate the rate of heat storage. At some point, related to the exercise intensity and absolute rate of heat production, the rate of heat dissipation will balance the rate of production and a new, elevated steady-state internal temperature will persist until some new perturbation is introduced. Stitt (1979), in differentiating the mechanisms that provide for the elevated internal temperatures of fever and exercise, represented the events that occur during exercise as described in this manner and shown in Fig. 1. During exercise there is no change in the regulated, or set point temperature; the hyperthermia is maintained by sustaining an error signal so that the rate of heat loss is driven to balance the rate of heat production. At the cessation of exercise the converse applies. The rate of heat loss is suddently much greater than the rate of heat production, thereby causing internal body temperature to fall toward the regulated level. As the temperature returns to this level, the heat dissipation systems are driven 165
166
ETHAN R. NADEL
HEAT ,'~,~ PRODUCT~,tON ,," HEAT LOSS
r
p ..........
---~-- -. I -
J..................
/t/T¢ore SUSTAINED ERROR SIGNAL
-
~Tse t +
~ I x
RATE OF
o,
1 \ 7
'"0"`°.
Fig. 1. A schematic representation of the thermal and energetic fluxes during the on-transient of exercise. See text for more detailed description. From Stitt (1979) with permission from the Federation of American Societies for Experimental Biology.
less vigorously and the rate of temperature change gradually diminishes, until eventually a steady state is once again established. In recent years there has been much research concern with the factors that affect the steady state of body temperature during exercise. Of particular interest has been the study of temperature regulation in subjects becoming (or rendered) progressively dehydrated. It has been well established that water restriction during prolonged exercise, especially in a warm environment, will result in a continuous increase in deep-body temperature, whereas fluid replacement will allow a steady state to be achieved (Pitts et al., 1944; Buskirk et al., 1958: Moroff & Bass, 1965). This either constitutes an exception to the Nielsen observation of a predictable increase in internal temperature during exercise or implies that a factor associated with the state of body hydration influences the temperature regulatory system. If the latter be correct, either increased blood osmolality or reduced blood volume (or both) could be affecting thermoregulatory activity from within the CNS or by damping effector organ responsiveness to a given signal. Of the more recent studies in this area, most (e.g. Greenleaf & Castle, 1971; Nielsen et al., 1971; Horstman & Horvath, 1972) but not all (Kitzing et al., 1971) have documented the phenomenon of progressive hyperthermia with progressive dehydration and have (logically enough) attributed the excess hyperthermia to failure of adequate peripheral circulatory and/or "sweating responses to the increased thermal load. Nonetheless, among the first investigations attempting to uncover a specific mechanism, rather than attempting to correlate increased blood osmolality or reduced volume with the change in internal body temperature, was that of Harrison et al. (1978). Prior to having their subjects exercise, they manipulated the volume and tonicity of the blood in one of three ways in order to separate potential effects of each. They found that body-core temperatures were relatively higher during exercise when dehydrated and
when dehydration was prevented by administration of 1°,, saline (hyperosmolar normovolemia) than during exercise when water was administered and plasma osmolality was maintained around control levels. They concluded that the higher temperatures were related to the elevated [Na*] and not to the change in volume, since they could demonstrate no consistent relation between temperature and volume. Senay (1968) had previously reported that the rate of weight loss during progressive dehydration was inversely correlated with both the serum [Na +] and osmolarity. Although the exposures involved some exercise, no body-temperature measurements were made and thus we can only conjecture that the reduced sweating caused elevations in internal temperature, given constant conditions. In the Harrison et al. study, no estimates of the heat flux were made. Thus, although it could be concluded that the temperatures were higher and the higher temperatures were associated with increased [Na +], the mechanism of action of the elevated [Na +] on the temperature regulatory system was still unexplored. Very recently we published the results of a study whose purpose was to examine the effect of reduced blood volume on the temperature regulatory system during exercise (Nadel et at., 1980). Contrary to the manipulations in the Harrison et al. study, we modified blood volume prior to exercise but maintained blood osmolality at control levels. This was accomplished by dehydrating subjects over 4 days with diuretics (triamterene and hydrochlorothiazide). Subjects were incapable of achieving a steady state in internal body (oesophageal) temperature (Tes)in either normovolemic or hypovolemic conditions during moderate exercise (55~ 12o~max) in the heat (35°C, water vapour pressure 16torr). When hypovolemic (blood volume reduced by 11~o), subjects had a much greater heat storage rate during the early transient of exercise, and after 30 min the Tes was 38.81 + 0.22°C, significantly higher than when normovolemic, when Tes was 38.44 + 0.07°C. The increased rate of heat storage during the early minutes of exercise could have been the consequence of an increase in the internal temperature threshold for the heat-dissipation responses and/or a reduced sensitivity of the response per unit of increased thermoregulatory drive. In this study we showed that hypovolemia induced a marked elevation in the internal temperature threshold for cutaneous vasodilation, from 36.90 + 0.06°C to 37.32 + 0.08°C (Fig. 2). This means that during the first minutes of exercise, the heat produced in the muscles was sequestered in the body core in hypovolemic subjects rather than transferred to the skin, as it was when they were normovolemic. Once cutaneous vasodilation was initiated, there was a small reduction in the sensitivity of the reflex, from 18.5 + 2.3 to 14.4 + 2.3 ml. min- 1. 100 ml- a. °C- 1. More importantly, hypovolemia reduced the maximal forearm blood flow from 18.6 to less than 13 ml. min- ' . 100 ml- 1, a reduction to around 70~o of the heat-flux capability of the cutaneous circulation in these conditions. Whereas the increase in threshold could be thought of as a thermoregulatory reflex responsive to signals related to the reduced blood volume (reduced cardiac filling pressure, for instance), the decrease in maximal cutaneous flow is likely the
Regulation of body temperature during exercise
167
'?', n=4
55% VO2 m o t T o - 35"C '
20
~L
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~ ~o o
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/
s
36.~
1 37.0
I 37.5
I 380
I 38.5
I 39.0
Oesophogeot Temperature, •C
Fig. 2. Forearm blood flow as a function of oesophageai temperature during exercise in the heat in control and hypovolemic conditions. Data points are averages 4- $E from linear regression analyses of 8 experiments in each condition. Modified from Nadel et aL (1980g
result of a baroreflex, acting to maintain arterial blood pressure in the face of a reduced central circulating blood volume. Both of these modifications in the core-to-skin heat-flux response contribute to the excessive hyperthermia during exercise in the heat. We have also observed modifications in the control of local sweating rate in subjects exercising when hypovolemic (Fortney et al., 1981). These were manifested primarily as a decrease in the sensitivity of the response per unit of internal temperature increase. With this information alone it is difficult to conclude whether there is a reduction in sweat-gland response to a given thermoregulatory drive or a competition for thermoregulatory drive within the central intcgrative centre. A reduction in the sensitivity of the sweating response, however, easily could contribute to the increased heat storage during the early transient of exercise, since this would extend the time necessary to achieve the steady state. These data indicate that hypovolemia per se is sufficient to stimulate the reduction in the cutaneous blood-flow response to body heating; hyperosmolality is not a requisite. The Harrison et al. (1978) report indicates that hyperosmolality per se is associated with excessive hyperthermia in partially-dehydrated subjects. In preliminary reports we have also shown that hyperosmolality affects the body's heat-transfer rates by increasing the internal temperature threshold for cutaneous vasodilation (Nadel, 1980; Fortney et al., 1982), as well as for sweating rate (Fortney et al., 1982). An example of this phenomenon is shown in Fig. 3. There were no modifications in the sensitivity of either the cutaneous blood flow or sweating rate increases per unit of internal temperature increase, implying that the reductions in heat flux at a given internal temperature were mediated by a direct ionic
effect within the thermoregulatory centre rather than at the periphery. The observations that either reduced blood volume or increased blood osmolality can act to conserve central circulating blood volume and body water in given conditions provide yet another example of the redundancy in physiological control
SUBJECT, EO
~ '~ ~ '~E t o o ~ ,, = • o.~ e° '= ~ .~ o.ao ; ~" 0.4o ,-e o o.~o
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Fig. 3. Sweating rate and forearm blood flow as a function of oe~phageal temperature during exercise in the heat (60~ 14:)2 max, 35°C) in control and hypertonic (osmo = 294 mosmol, kg- t) conditions. Data are from a representative subject.
168
ETHAN R. NADEL
systems; during progressive dehydration, as occurs with prolonged exercise in the heat for instance, both a reduction in blood volume and an increase in blood osmolality occur. Either can trigger the appropriate compensatory reflex that attenuates the temperature regulatory response to body heating. In conclusion, the regulation of body temperature during exercise is achieved via a system involving several orders of complexity. At the simplest level, the increase in internal body temperature caused by the convection of heat from the contracting muscles is sensed and compared with idealized information within the thermoregulatory centre. A central thermoregulatory drive to the organs of heat dissipation results when internal temperature exceeds the "'regulated" or "set point" temperature. The new steadystate internal temperature is then largely a function of the sensitivity, or quickness, of the efferent systems: the lower the sensitivity the longer the time to steady state, the greater the absolute heat storage and therefore the higher the internal temperature in any individual. The second level of complexity involves factors that can alter the quickness of the efferent response. We have dealt with some of these in the past and summarized our findings in a brief review a few years ago (Nadel et al., 1977). These factors include such physical characteristics of the environment as ambient humidity and air velocity, that translate their effects onto the body by affecting the skin wetness. They also include the level of physical condition of the subject; the fitter the individual, the steeper the gain of the sweating response and the more rapidly the achievement of a steady state in internal body temperature at a given exercise intensity (i.e. the lower the steadystate temperature). The third level of complexity includes the interactions that the temperature regulatory system has with other regulatory systems. The control of skin vasomotor activity is the shared effector loop of two regulatory systems---systems involved in regulation of
body temperature and in regulation of blood pressure (Fig. 4). The muscular activity of exercise applies a load to both systems, inducing a thermal load proportional to the exercise intensity and a volume load (reduction in central blood volume) that is also related to the exercise intensity. Demands from the blood-pressure control loop compete with those from the loop calling for increased heat transfer and a compromise is struck. When the drive for skin blood flow is great, as with high internal and skin temperatures (heavy exercise in the heat), cardiac filling pressure is progressively reduced and a cutaneous vasconstrictor drive is superimposed upon the dilator drive to skin vessels. This redirects blood flow centrally but imposes a limitation in the rate of heat flow from coreto-skin. Further reductions in central blood volume, such as occur with the progressive dehydration accompanying prolonged exercise (fluid is lost from all body compartments) and pooling of blood in cutaneous veins, tend to result in a partial inhibition of thermoregulatory drive, as evidenced from a higher threshold for cutaneous vasodilation. Increased blood osmolality also has the effect of partially inhibiting the outflow from the thermoregulatory centre to the efferent organs. Inhibition in both cases is overridden when the drive becomes sufficiently strong. In either case the steady-state internal temperature must be higher than in the normovolemic condition if a steady state can be achieved. Further research in this area will reveal whether the signals affecting the thermoregulatory centre are entirely neural or whether there is a hormonal component involved in the integrated response.
Acknowledgement--Supported in part by the U.S. National Institutes of Health Grants HL-20634 and HL-17732. REFERENCES
BUSKIRKE. R., IAMPIETROP. F. & BASSD. E. (1958) Work performance after dehydration: effect of physical condi-
Introvosculor stretch q receptors
osmoreceptors (
~) ar terlol end/or cardiac filling pressures
(~) osrnotollty
® vesomotot
,® ~ntre
thermorlgulotory
,®
centre
(~)
sweet 91and activity
body temperatures body thermoreceptars
~(
Fig. 4. A schematic representation of the systems controlling body temperature and blood pressure, illustrating the common link of cutaneous vasomotor tone. See text for more detail. Modified from Nadel (1980).
Regulation of body temperature during exercise tioning and heat acclimatization. J. appl. PhysioL 12, 189-194. CABANAC M.. CUNNINGHAM D. J. & STOLWlJK J. A. J. ( 1971) Thermoregulatory set point during exercise: a behavioral approach. J. comp. physioL PsychoL 76, 94-102. FORTNEV S. M., NADEL E. R., WENGER C. B. & BOVE J. R. (1981) Effect of blood volume on sweating rate and body fluids in exercising humans. J. appl. PhysioL 51. 1594-1600. FOgTNEY S. M.. WENGER C. B.. BOVE J. R. & NADEL E. R. (19821 Effect of plasma osmolality on peripheral blood flow and body sweating during exercise. Fedn Proc. 41, 1348. GREENLEAF J. E. & CASTLE B. L. (1971) Exercise temperature regulation in man during hypohydration and hyperhydration. J. appl. Physiol. 30, 847-853. HARRISON M. H., EDWARDS R. J. & FENNESSY P. A. (1978) Intravascular volume and ton(city as factors in the regulation of body temperature. J. appl. Physiol. 44, 69-75. HORSTMAN D. H. & HORVATH S. M. (1972) Cardiovascular and temperature regulatory changes during progressive dehydration and euhydration. J. appl. Physiol. 33, 446-450. KITZING J., BEHL1NG K,, BLEICHERT A., NINOW S., SCARPERI M. & SCARPERI S. {1971) Correlations between input and output of the thermoregulatory control systems during rest and exercise Int. J. Biomet. 15. 207-211. MOROEF S. E. & BASS D, E. (1965) Effects of overhydration on man's physiological response to work in the heat. J. appl. Physiol. 20, 267-270. NADEL E. R. (1980) Circulatory and thermal regulations during exercise. Fedn Proc. 39, 1491-1497. NADEL E. R., BULLARD R. W. & STOLWIJK J. A. J. (1971)
T.B. 8 - I 2 - - L
169
Importance of skin temperature in the regulation of sweating. J. appl. Physiol. 31, 80-87. NADEL E. R., WENGER C. B., ROBERTS M. F., STOLWIJK J. A. J. ~ CAFARELLI E.
(1977) Physiological
defenses
against the hyperthermia of exercise. Ann. N. E Acad. Sci. 301, 98-109. NADEL E. R.. FORTNEY S. M. & WENGER C. B. 119801 Effect of hydration state on circulatory and thermal regulations. J. appl. Physiol. 49, 715-721. NIELSEN B. 8:,, NIELSEN M, (1965) Influence of passive and active heating on the temperature regulation of man. Acta physiol, scand. 64, 323-331. NIELSEN B., HANSEN G., JORGENSEN S. O. & NIELSEN E.
(1971) Thermoregulation in exercising man during dehydration and hyperhydration with water and saline. Int. J. Biomet. 15, 195-200. NIELSEN M. (1938) Die Regulation der Korpertemperatur be( Muskelarbeit. Skand. Arch. Physiol. 79, 193-230. PITTS G. C.. JOHNSON R. E. & CONSOLAZIO F. C. (1944) Work in the heat as affected by intake of water, salt and glucose. Am. J. Physiol. 142, 253-259. ROmNSON S. (1949) Physiological adjustments to heat. In Physiology of Heat Regulation and the Science c?f CIothin 0 (Edited by NEWBURGH U H.k pp. 193-231. Saunders, Philadelphia. SENAY L. C. JR (1968) Relationship of evaporative rates to serum l-Na], [K] and osmolarity in acute heat stress. J. appl. Physiol. 25, 149-152. STITT J. T. (1979) Fever versus hyperthermia. Fedn Proc. 38, 39-43.
Key Word lndex--Thermoregulation: dration; hyperthermia.
exercise: dehy-
0306-4565/83/010165-05505.00;0 Copyright © 1983 Pergamon Press Ltd
Printed in Great Britain. All rights reserved
REVIEW FACTORS AFFECTING THE REGULATION OF BODY TEMPERATURE D U R I N G EXERCISE ETHAN R. NADEL John B. Pierce Foundation Laboratory and Departments of Epidemiology and Public Health and Physiology, Yale University School of Medicine, New Haven, CT 06519 U.S.A. Abstract--1. During exercise, the heat produced in the contracting muscles causes internal body temperature to rise until the heat-dissipation responses, increasingly driven by the rising temperature, provide for a new balance between heat-production and heat-loss rates. 2. The new elevated steady-state internal body temperature is not invariant, but can be affected by a number of factors, such as wetness of the skin or state of body hydration. 3. Progressive dehydration, such as occurs during prolonged exercise or exercise in the heat, results in relative hyperthermia caused by increased thresholds and decreased sensitivities of the heat-dissipation mechanisms. Independent manipulations of blood volume and osmolality reveal that these variables exert their effects on the thermoregulatory system by somewhat different means.
DURING exercise, heat is produced in the contracting muscles at a rate proportional to the exercise intensity. Fit individuals are able to sustain a rate of heat production in excess of 1200W (15 times the basal rate) for extended periods. Practically all of this heat is convected to the body core in the venous return of blood from the muscles, and most of this heat is rapidly dissipated to the environment by radiation, convection and/or evaporation. Without an efficient temperature regulatory system, involving elements that sense the increased body temperatures, elements that evaluate the body-temperature elevations and elements that provide for increased heat-transfer rates from core-to-skin and from skin-to-environment, heavy exercise or exercise in the heat would be limited to 10--15 min by excessive hyperthermia. It is now well known that M. Nielsen (1938) was the first to thoroughly describe the observation that internal body temperature increases during muscular exercise and eventually arrives at a new steady state that is roughly proportional to the absolute exercise intensity and independent of the ambient temperature (between 5 and 30°C, at least). Nielsen interpreted these data as indicating that the increase in internal temperature was a regulated one, caused by a new, higher body temperature set point during exercise. About a decade later Robinson (1949) published an extremely comprehensive review on the topic of physiological adjustments to heat and exercise. Robinson showed that the sweating rate during exercise could be described by a proportional control model. Sweating rate was found to be a linear function of internal body temperature; the average skin temperature was also found to affect sweating rate, although to a much lesser extent per degree change than internal temperature. Skin temperature changes served to adjust the internal temperature threshold for sweating. Robinson concluded that the "... rise in sweating apparently was a direct effect of internal temperature on the heat regulatory centers (sic.) and was possibly due also to stimulation of the centers
resulting from the increasing neuromuscular activity." In other words, Robinson appears to have claimed that the internal temperature increase was the primary drive for the sweating response and, further, although he had no evidence for such an effect, that sweating activity might be influenced by factors related to the exercise itself. With Robinson's model, since confirmed and expanded upon by others (e.g. Nadel et al., 1971), there is no need to postulate an altered "'set point" during exercise, and indeed, there is now an accumulated body of evidence against this concept (Nielsen & Nielsen, 1965; Cabanac et al., 1971; Stitt, 1979). The elevated internal temperature is a consequence of the temporary imbalance between the rates of heat production and heat dissipation. At the onset of exercise the body's rate of heat production suddenly is much greater than the rate of dissipation and the extra heat is stored, thereby causing internal body temperature to rise. The rise in internal temperature initiates increases in cutaneous blood flow and sweating rate and these activated heat-dissipation responses attenuate the rate of heat storage. At some point, related to the exercise intensity and absolute rate of heat production, the rate of heat dissipation will balance the rate of production and a new, elevated steady-state internal temperature will persist until some new perturbation is introduced. Stitt (1979), in differentiating the mechanisms that provide for the elevated internal temperatures of fever and exercise, represented the events that occur during exercise as described in this manner and shown in Fig. 1. During exercise there is no change in the regulated, or set point temperature; the hyperthermia is maintained by sustaining an error signal so that the rate of heat loss is driven to balance the rate of heat production. At the cessation of exercise the converse applies. The rate of heat loss is suddently much greater than the rate of heat production, thereby causing internal body temperature to fall toward the regulated level. As the temperature returns to this level, the heat dissipation systems are driven 165
166
ETHAN R. NADEL
HEAT ,'~,~ PRODUCT~,tON ,," HEAT LOSS
r
p ..........
---~-- -. I -
J..................
/t/T¢ore SUSTAINED ERROR SIGNAL
-
~Tse t +
~ I x
RATE OF
o,
1 \ 7
'"0"`°.
Fig. 1. A schematic representation of the thermal and energetic fluxes during the on-transient of exercise. See text for more detailed description. From Stitt (1979) with permission from the Federation of American Societies for Experimental Biology.
less vigorously and the rate of temperature change gradually diminishes, until eventually a steady state is once again established. In recent years there has been much research concern with the factors that affect the steady state of body temperature during exercise. Of particular interest has been the study of temperature regulation in subjects becoming (or rendered) progressively dehydrated. It has been well established that water restriction during prolonged exercise, especially in a warm environment, will result in a continuous increase in deep-body temperature, whereas fluid replacement will allow a steady state to be achieved (Pitts et al., 1944; Buskirk et al., 1958: Moroff & Bass, 1965). This either constitutes an exception to the Nielsen observation of a predictable increase in internal temperature during exercise or implies that a factor associated with the state of body hydration influences the temperature regulatory system. If the latter be correct, either increased blood osmolality or reduced blood volume (or both) could be affecting thermoregulatory activity from within the CNS or by damping effector organ responsiveness to a given signal. Of the more recent studies in this area, most (e.g. Greenleaf & Castle, 1971; Nielsen et al., 1971; Horstman & Horvath, 1972) but not all (Kitzing et al., 1971) have documented the phenomenon of progressive hyperthermia with progressive dehydration and have (logically enough) attributed the excess hyperthermia to failure of adequate peripheral circulatory and/or "sweating responses to the increased thermal load. Nonetheless, among the first investigations attempting to uncover a specific mechanism, rather than attempting to correlate increased blood osmolality or reduced volume with the change in internal body temperature, was that of Harrison et al. (1978). Prior to having their subjects exercise, they manipulated the volume and tonicity of the blood in one of three ways in order to separate potential effects of each. They found that body-core temperatures were relatively higher during exercise when dehydrated and
when dehydration was prevented by administration of 1°,, saline (hyperosmolar normovolemia) than during exercise when water was administered and plasma osmolality was maintained around control levels. They concluded that the higher temperatures were related to the elevated [Na*] and not to the change in volume, since they could demonstrate no consistent relation between temperature and volume. Senay (1968) had previously reported that the rate of weight loss during progressive dehydration was inversely correlated with both the serum [Na +] and osmolarity. Although the exposures involved some exercise, no body-temperature measurements were made and thus we can only conjecture that the reduced sweating caused elevations in internal temperature, given constant conditions. In the Harrison et al. study, no estimates of the heat flux were made. Thus, although it could be concluded that the temperatures were higher and the higher temperatures were associated with increased [Na +], the mechanism of action of the elevated [Na +] on the temperature regulatory system was still unexplored. Very recently we published the results of a study whose purpose was to examine the effect of reduced blood volume on the temperature regulatory system during exercise (Nadel et at., 1980). Contrary to the manipulations in the Harrison et al. study, we modified blood volume prior to exercise but maintained blood osmolality at control levels. This was accomplished by dehydrating subjects over 4 days with diuretics (triamterene and hydrochlorothiazide). Subjects were incapable of achieving a steady state in internal body (oesophageal) temperature (Tes)in either normovolemic or hypovolemic conditions during moderate exercise (55~ 12o~max) in the heat (35°C, water vapour pressure 16torr). When hypovolemic (blood volume reduced by 11~o), subjects had a much greater heat storage rate during the early transient of exercise, and after 30 min the Tes was 38.81 + 0.22°C, significantly higher than when normovolemic, when Tes was 38.44 + 0.07°C. The increased rate of heat storage during the early minutes of exercise could have been the consequence of an increase in the internal temperature threshold for the heat-dissipation responses and/or a reduced sensitivity of the response per unit of increased thermoregulatory drive. In this study we showed that hypovolemia induced a marked elevation in the internal temperature threshold for cutaneous vasodilation, from 36.90 + 0.06°C to 37.32 + 0.08°C (Fig. 2). This means that during the first minutes of exercise, the heat produced in the muscles was sequestered in the body core in hypovolemic subjects rather than transferred to the skin, as it was when they were normovolemic. Once cutaneous vasodilation was initiated, there was a small reduction in the sensitivity of the reflex, from 18.5 + 2.3 to 14.4 + 2.3 ml. min- 1. 100 ml- a. °C- 1. More importantly, hypovolemia reduced the maximal forearm blood flow from 18.6 to less than 13 ml. min- ' . 100 ml- 1, a reduction to around 70~o of the heat-flux capability of the cutaneous circulation in these conditions. Whereas the increase in threshold could be thought of as a thermoregulatory reflex responsive to signals related to the reduced blood volume (reduced cardiac filling pressure, for instance), the decrease in maximal cutaneous flow is likely the
Regulation of body temperature during exercise
167
'?', n=4
55% VO2 m o t T o - 35"C '
20
~L
E
0 9
,ht•, T I I -
T
E
Js
E
CONTRO/
o
/ / ~ ' ~ ' - " - m - ~
[,
/
~ ~o o
[ ~.
/
s
36.~
1 37.0
I 37.5
I 380
I 38.5
I 39.0
Oesophogeot Temperature, •C
Fig. 2. Forearm blood flow as a function of oesophageai temperature during exercise in the heat in control and hypovolemic conditions. Data points are averages 4- $E from linear regression analyses of 8 experiments in each condition. Modified from Nadel et aL (1980g
result of a baroreflex, acting to maintain arterial blood pressure in the face of a reduced central circulating blood volume. Both of these modifications in the core-to-skin heat-flux response contribute to the excessive hyperthermia during exercise in the heat. We have also observed modifications in the control of local sweating rate in subjects exercising when hypovolemic (Fortney et al., 1981). These were manifested primarily as a decrease in the sensitivity of the response per unit of internal temperature increase. With this information alone it is difficult to conclude whether there is a reduction in sweat-gland response to a given thermoregulatory drive or a competition for thermoregulatory drive within the central intcgrative centre. A reduction in the sensitivity of the sweating response, however, easily could contribute to the increased heat storage during the early transient of exercise, since this would extend the time necessary to achieve the steady state. These data indicate that hypovolemia per se is sufficient to stimulate the reduction in the cutaneous blood-flow response to body heating; hyperosmolality is not a requisite. The Harrison et al. (1978) report indicates that hyperosmolality per se is associated with excessive hyperthermia in partially-dehydrated subjects. In preliminary reports we have also shown that hyperosmolality affects the body's heat-transfer rates by increasing the internal temperature threshold for cutaneous vasodilation (Nadel, 1980; Fortney et al., 1982), as well as for sweating rate (Fortney et al., 1982). An example of this phenomenon is shown in Fig. 3. There were no modifications in the sensitivity of either the cutaneous blood flow or sweating rate increases per unit of internal temperature increase, implying that the reductions in heat flux at a given internal temperature were mediated by a direct ionic
effect within the thermoregulatory centre rather than at the periphery. The observations that either reduced blood volume or increased blood osmolality can act to conserve central circulating blood volume and body water in given conditions provide yet another example of the redundancy in physiological control
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168
ETHAN R. NADEL
systems; during progressive dehydration, as occurs with prolonged exercise in the heat for instance, both a reduction in blood volume and an increase in blood osmolality occur. Either can trigger the appropriate compensatory reflex that attenuates the temperature regulatory response to body heating. In conclusion, the regulation of body temperature during exercise is achieved via a system involving several orders of complexity. At the simplest level, the increase in internal body temperature caused by the convection of heat from the contracting muscles is sensed and compared with idealized information within the thermoregulatory centre. A central thermoregulatory drive to the organs of heat dissipation results when internal temperature exceeds the "'regulated" or "set point" temperature. The new steadystate internal temperature is then largely a function of the sensitivity, or quickness, of the efferent systems: the lower the sensitivity the longer the time to steady state, the greater the absolute heat storage and therefore the higher the internal temperature in any individual. The second level of complexity involves factors that can alter the quickness of the efferent response. We have dealt with some of these in the past and summarized our findings in a brief review a few years ago (Nadel et al., 1977). These factors include such physical characteristics of the environment as ambient humidity and air velocity, that translate their effects onto the body by affecting the skin wetness. They also include the level of physical condition of the subject; the fitter the individual, the steeper the gain of the sweating response and the more rapidly the achievement of a steady state in internal body temperature at a given exercise intensity (i.e. the lower the steadystate temperature). The third level of complexity includes the interactions that the temperature regulatory system has with other regulatory systems. The control of skin vasomotor activity is the shared effector loop of two regulatory systems---systems involved in regulation of
body temperature and in regulation of blood pressure (Fig. 4). The muscular activity of exercise applies a load to both systems, inducing a thermal load proportional to the exercise intensity and a volume load (reduction in central blood volume) that is also related to the exercise intensity. Demands from the blood-pressure control loop compete with those from the loop calling for increased heat transfer and a compromise is struck. When the drive for skin blood flow is great, as with high internal and skin temperatures (heavy exercise in the heat), cardiac filling pressure is progressively reduced and a cutaneous vasconstrictor drive is superimposed upon the dilator drive to skin vessels. This redirects blood flow centrally but imposes a limitation in the rate of heat flow from coreto-skin. Further reductions in central blood volume, such as occur with the progressive dehydration accompanying prolonged exercise (fluid is lost from all body compartments) and pooling of blood in cutaneous veins, tend to result in a partial inhibition of thermoregulatory drive, as evidenced from a higher threshold for cutaneous vasodilation. Increased blood osmolality also has the effect of partially inhibiting the outflow from the thermoregulatory centre to the efferent organs. Inhibition in both cases is overridden when the drive becomes sufficiently strong. In either case the steady-state internal temperature must be higher than in the normovolemic condition if a steady state can be achieved. Further research in this area will reveal whether the signals affecting the thermoregulatory centre are entirely neural or whether there is a hormonal component involved in the integrated response.
Acknowledgement--Supported in part by the U.S. National Institutes of Health Grants HL-20634 and HL-17732. REFERENCES
BUSKIRKE. R., IAMPIETROP. F. & BASSD. E. (1958) Work performance after dehydration: effect of physical condi-
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Regulation of body temperature during exercise tioning and heat acclimatization. J. appl. PhysioL 12, 189-194. CABANAC M.. CUNNINGHAM D. J. & STOLWlJK J. A. J. ( 1971) Thermoregulatory set point during exercise: a behavioral approach. J. comp. physioL PsychoL 76, 94-102. FORTNEV S. M., NADEL E. R., WENGER C. B. & BOVE J. R. (1981) Effect of blood volume on sweating rate and body fluids in exercising humans. J. appl. PhysioL 51. 1594-1600. FOgTNEY S. M.. WENGER C. B.. BOVE J. R. & NADEL E. R. (19821 Effect of plasma osmolality on peripheral blood flow and body sweating during exercise. Fedn Proc. 41, 1348. GREENLEAF J. E. & CASTLE B. L. (1971) Exercise temperature regulation in man during hypohydration and hyperhydration. J. appl. Physiol. 30, 847-853. HARRISON M. H., EDWARDS R. J. & FENNESSY P. A. (1978) Intravascular volume and ton(city as factors in the regulation of body temperature. J. appl. Physiol. 44, 69-75. HORSTMAN D. H. & HORVATH S. M. (1972) Cardiovascular and temperature regulatory changes during progressive dehydration and euhydration. J. appl. Physiol. 33, 446-450. KITZING J., BEHL1NG K,, BLEICHERT A., NINOW S., SCARPERI M. & SCARPERI S. {1971) Correlations between input and output of the thermoregulatory control systems during rest and exercise Int. J. Biomet. 15. 207-211. MOROEF S. E. & BASS D, E. (1965) Effects of overhydration on man's physiological response to work in the heat. J. appl. Physiol. 20, 267-270. NADEL E. R. (1980) Circulatory and thermal regulations during exercise. Fedn Proc. 39, 1491-1497. NADEL E. R., BULLARD R. W. & STOLWIJK J. A. J. (1971)
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Importance of skin temperature in the regulation of sweating. J. appl. Physiol. 31, 80-87. NADEL E. R., WENGER C. B., ROBERTS M. F., STOLWIJK J. A. J. ~ CAFARELLI E.
(1977) Physiological
defenses
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Key Word lndex--Thermoregulation: dration; hyperthermia.
exercise: dehy-