S169
Mechanisms of Adaptation to Cold J. LeBlanc Department of Physiology, Faculty of Medicine, Laval University, Quebec City, GIK 7P4, Canada
Adaptation to Cold in Rats J. LeBlanc, Mechanisms of Adaptation to Cold. Tnt mt j. Cold. J. Sports Med, Vol 13, Suppl 1, pp S169—S172,
Most of the studies on the rat were done by placing placing them them at at 55 °C °C for for aa few few weeks. weeks. At At first first marked marked increases increases
in both adrenaline and noradrenaline are observed, adrenal
1992.
cortex is stimulated the animal loses weight and shivers; it is really a very stressing situation. After a few days the animals stop
The animal model used the most frequently for understanding the mechanisms of adaptation to cold in humans has been the rat. It has been established that rats kept in the cold for a few weeks stop shivering while preserving a normal internal temperature because of an enhanced thermogenic capacity of the brown adipose tissue (BAT) mediated by the sympathetic nervous system. Studies on groups of humans exposed to cold have shown that shivering is also attenuated but without compensatory increased in heat production possibly because of non-significant contribution of the BAT. However when humans and laboratory animals are exposed repeatedly to short severe
shivering, they eat more and body weight increases. At the
cold evidence for adaptation has been described. This adaptation is not metabolic; instead it is related to the phenomenon of habituation. When exposed to a novel stress such as cold, the alarm reaction is initiated as evidenced by the activation of the sympathetic nervous system which opposes the stressing situation. However with time, when it is realized that the normal functioning of the body is not endangered the responses are attenuated and enhanced tolerance is observed. This type type of of adaptation adaptation was was observed observedin in Eskimos, fishermen, outdoor workers, etc. Key words
Cold, adaptation, habituation, shivering
Introduction
It is often customary when you do clinical or applied research to look for an animal model. This has been the case for people working on adaptation to cold in humans. The animal which has been used for many years and by a large number of investigators is the rat. In a sense this choice made sense. It is true that the rat produces and loses much more heat per unit of body mass than than humans. humans. However However when when the the inincrease in heat production production due due to to cold cold is is expressed expressed as as aapercentpercentage of the resting metabolic rate, the response is comparable for both species; at 5 °C both rats and humans increase their
oxygen consumption by about 100% and both are comfortable when the room temperature is about 25 °C (8). On that basis both species may be used as models for one another. lnt.J.SportsMed. 13(1992)S169—S172 13(l992)S169—S172 New York GeorgThieme Verlag Stuttgart StuttgartNew
same time adrenaline in the blood which reflects the emotional component of the stress gradually declines. On the other hand plasma noradrenaline remains elevated as long as the animal is kept in the cold (18). The enhanced secretion of this kept this hormone, hormone, which reflects the activity of the sympathetic nervous system,
proved to be important in the processes of cold adaptation since the mere daily injections of noradrenaline for a few weeks to rats kept at room temperature, was sufficient to signif-
icantly improve cold tolerance in these animals which had never been exposed to cold before (15, 16). These findings found their explanation in studies on brown adipose tissue and which kept many scientists busy for many years. Essentially it has been shown that when exposed to cold rats become more tolerant because of a sustained stimulation of this tissue by the sympathetic nervous system. Indeed the BAT becomes highly thermogenic to the extent that the animals can remain in the cold without shivering (4). This is really an efficient adaptive tive process because shivering shivering isis not not aavery veryefficient efficientway wayofofproproducing ducing heat and besides that, it is an unpleasant and and disturbing disturbing experience.
Adaptation to Cold in Humans (Moderate Cold Exposure) Is the rat a good model for humans? In the fifties a few researchers, and I was one of them, started looking for populations who were living in a cold environment. Expeditions were organized for the Arctic, Antarctic, Australia and the Kalahari desert. It was found that Australian aborigenes, Kalahari bushmen or soldiers exposed to an Arctic environment during the winter, shivered less than subjects living 'iving in a temperate climate when exposed to a standard cold test (7, 12, 20, 22). These populations were more comfortable and were 20, 22). able to sleep without shivering the same as the rat. However humans and its model the rat, achieved the same aim aim but but by by
different strategies. In the rat shivering is replaced by non shivering thermogenesis which originates in the brown adipose tissue. Humans adapted to cold shiver less upon expo-
sure to a standard test and their heat production is reduced; they do not compensate by non-shivering thermogenesis. As a result there is a slight fall in deep body temperature which did not prove detrimental in the circumstances under which the experiments were done.
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Abstract
5170 mt. J. Sports Med. 13(1992)
Does that mean that there is no brown fat in humans and that it cannot be switched on by exposure to cold? There is evidence for active brown fat in newborn humans and in people with pheochrornocytorna. pheochromocytorna. In normal adults the evidence is very thin if not lacking. It is possibly because humans are not exposed to low temperatures for sufficiently long period of time to activate the brown fat. Taken together the re-
suits sults obtained on rats and humans may indicate that we are dealing with different mechanisms for the induction of BAT and for the reduction of shivering found in cold adaptation. Indeed in humans there is no evidence of non-shivering thermogenesis due to BAT activation, yet as was observed in Aborigines they stop shivering in the cold.
b) Role of habituation
It has been suggested that the diminution of shivering and of discomfort are due to habituation, that is to a
centrally controlled negative reflex conditioning (6, 12). It seems as if the organism, when exposed to moderate cold for varying periods of time, learns that the situation is not dangerous and that the discomfort of shivering is really not necessary. In other words our system can differentiate between the emi-
nence of a catastrophe and the occurrence of a mere inconvenience and unconsciously reacts accordingly. This phenomenon has been called habituation. There is yet another possi-
bility of explaining at least in the rat, the disappearance of shivering when the animal is adapted to cold. Brflck Brück has has shown shown
that the elevation of temperature in the vicinity of the spinal cord specially at the level of the interscapular brown fat prevents the activation of spinal cord cold receptors and abolishes shivering (2). In other words as adaptation progresses, the BAT starts producing more heat and this would prevent shivering by blocking the spinal cord cold receptor stimulation. Adaptation to Cold (Severe Cold Exposure)
a) Human studies I would like now to raise the following question: What happens when human subjects or rats are exposed to more severe cold? Is habituation sufficient and is adaptation to cold still possible? Let us compare an experiment done
on humans exposed repeatedly to cold and another one on rats. Young and collaborators studied (on 7 male subjects) the effects of water immersion (18 °C) for 1.5 hour per day, 5 days a week during 5 weeks (24). Before and after the end of the experiment the responses of the subjects to a cold air air exposure exposure
(5 °C) were measured. The measurements included inc]uded oxygen consumption, rectal and skin temperature, and plasma catecholamine determinations. The results show that the increase in oxygen consumption and the intensity of shivering upon cold air exposure are the same before as they are after the repeated cold water immersion in spite of a significantly larger increase in plasma norepinephrine during the last cold water immersion as compared to the first one. This finding suggests that the repeated activation of the sympathetic nervous system failed to induce non-shivering non-shivering thern-iogenesis thermogenesis in in these these subjects. subjects.
These findings do not argue in favor of the brown adipose tissue tissue participation participation in in humans. humans. These These results results also also show show that that the the subjects are as much disturbed by the stress, if not more, after repeated water immersion since the norepinephrine secretion is higher during the last exposure than in the first one. Habitua-
tion is not evident. However this study gives additional information. mation. At At the the end end of of the the experiment experiment when when the the subjects subjects are are exexposed to a standard cold test, both the skin and deep body temperatures are lower than at the beginning of the experiment.
One would expect, with lower skin temperature and comparable heat production, a higher rectal temperature in the adapted subjects. Since the rectal temperature is actually lower, one has to conclude conclude that that the the equation equation for for heat heat balance balance has changed. The authors rightly suggest a change in heat distribution function at at aa higher higher tribution whereby the muscle mass would function temperature. However the advantage of such changes in heat distribution is not obvious since the capacity to generate heat is
not modified at the end of the experiment in spite of higher plasma norepinephrine levels.
Rats studies Comparable studies were done on rats which were exposed to cold air (— 5 °C), two hours per day for one month (1). The increase increase in oxygen consumption caused by this (I). The exposure is similar to that reported in humans when immersed in water at 18 °C; in both situations the increase is about 100% above resting values. At the end of the adaptation period, the brown adipose tissue mass increased by 50%, while a 2.5 fold
increase in the protein and DNA contents were measured. Contrary to what is found in humans, non-shivering thermogenesis develops in rats exposed to short repeated exposure to cold and their resistance to this stress is significantly improved. Adaptation to Cold (Short Severe Exposures)
a) Human studies There is another type of cold exposure which causes very little metabolic responses. It is the one produced by short local exposure to cold conditions. These are observed in regions where temperatures fall below zero in the winter and with varying wind velocity. If a person is well dressed and is somewhat active there will be no extra heat required to resist cold and for that reason adaptive metabolic responses should not be expected. However this person may encounter various degrees of cold discomfort since it is sometimes difficult to adequately protect the face and the extremities. When this occurs discomfort is experienced and the sympathetic nervous system is activated as evidenced by the elevation of plasma cate-
cholamines and the cardiovascular responses such as increased heart rate, blood pressure and peripheral resistance. In many of these situations adaptation to cold has been been obobserved and it has been described as habituation. Many groups have been studied such as students, soldiers, Eskomos, Gaspé fishermen, etc. (13). A standardized test for measuring the response to local cold exposure has been the so-called cold pressor test which consists in immersing the hand into cold water for a few minutes.
An example of this type of adaptation was ob-
served in Gaspé fishermen (10, 14). When their hands are placed in cold water, they experienced very little discomfort and a small rise in blood pressure. However these same subjects when tested for metabolic adaptation by exposure to a 10 °C temperature for one hour shivered even more than control subjects and their average skin temperature was higher. These findings are likely explained by the fact that Gaspé fishermen in the traditional way way of of fishing fishing repeatedly repeatedly immersed immersed
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a) Role of brown adipose tissue
J. LeBlanc
mt. J. Sports Med.13 13(1992) (1992) S171 S171 Int.J.SportsMed
Mechanisms ofAdaptation to Cold
Animal studies Similar studies were done on laboratory animals and the results obtained clearly differentiate between habituation and metabolic adaptation to cold (11, 17). Mice or
rats were exposed for 10 minutes to temperatures as low as — day 20 °C at hourly intervals for a total of 9 exposures per day —20 during during two two consecutive consecutive days. days. On On the the third third day day their their tolerance tolerance to cold was tested by measuring the fall in rectal temperature or the the survival survival at at low low temperatures. temperatures. Tolerance Tolerance to to cold cold was was signifisignificantly improved in animals repeatedly exposed for short periods to very low temperatures. temperatures. The The response response to to norepinephrine norepinephrine which is greatly increased in rats adapted by continuous exposure (3—4 weeks) to moderate cold (5 °C), because of enhanced thermogenic capacity of the BAT, was found to be the same in
control and habituated rats. What causes the improved cold tolerance of habituated animals? In 1957 Glaser and co-workers followed the heart rate increase when the tails of rats are placed in cold water (4 °C) daily for 10 days (5). They reported a gradual decline in the cardiac response. However they found that rats with frontal cortical lesions failed to adapt to the same exposures. The authors concluded to a central control for this
type of adaptation. We also found significant changes in the responses of the autonomic autonomic nervous nervous system. system. During During the thecold cold resistance test a 4-fold increase in epinephrine excretion was found in control animals, but the values for the habituated rats were within normal range (11). Similar findings were reported in humans when exposed many times to a centrifugation test. However with repeated parachute jumping epinephrine excretion remained high and von Euler concluded from these findings that habituation does not take place if an element of real real danger danger persists persists (23). (23). Since Since the the emotional emotional component component of of aa stress is reflected by an increased secretion of epinephrine, it is suggested that with habituation this component is gradually reduced. It is not known how this response could improve cold tolerance. It is interesting to note that habituation to stresses which do not depend on the heat producing capacity of the animals, has also been described. Rats placed at high altitude (30,000 feet) for 10 minutes, 9 times per day for 2 days were also shown to be much more resistant to hypoxia than control animals (9). These various studies suggest that upon exposure to a novel stress with which we are not familiar and not knowing whether it will be harmful or not, defence mechanisms such as as the the increased increased activity activity of of the the sympathetic sympathetic nervous nervous syssyssuch tem are activated. The amplitude of this response may be exaggerated at first and for that reason it may even be detrimental. But when it is realized after many exposures that the stress will
not cause damage to the organism, the responses are attenuated and improved tolerance i.e. adaptation is observed.
Adaptation to Cold and the Heat Stress Proteins
There is another area of research, recently developed which may have some implication in the process of
cold adaptation. Mammalian cells have been shown to become very tolerant to thermal damage when they are previously conditioned to high temperatures (41 °C) for short periods. There is now much evidence suggesting that certain proteins, particularly the 70 kDA, are involved in this process of improved resistance. These proteins have been termed the heat shock proteins (HSP). However since the HSP response has also been observed with many agents such as ethanol, inhibitors of mitochondrial function or viral infections it is suggested that these proteins be referred to as the stress protein. The synthesis of HSP is a non-specific stress response since it has been observed observed not not only only with with heat heat but but also also with with many many stress stress includinclud-
ing hypoxia. Furthermore the increased resistance to hypothermia in Drosophila which had been previously exposed to heat (3) suggests an interstress resistance which is possibly related related to to HSP HSP synthesis. synthesis. The The lethal lethal effect effect of of stress stress has has been been atattributed to the synthesis of HSP. Hoever there is some evidence showing that this protein is involved in the regulation of its own synthesis (19). As a result exposure to heat stress for ex-
ample increases 70K stress protein but the synthesis of this protein would be significantly reduced during a subsequent exposure to heat (21). Similar studies with cold stress have not
been reported but it would be interesting to see if previous lowering of tissue temperature temperature would would subsequently subsequently improve improve their tolerance to cold. References
2
Exercise during intermittent intermittent cold cold exposure exposure Arnold J., Richard D.: D.: Exercise prevents acclimation to cold rats. J Physiol 390:45—54, 1987. Brück K.: K.: Non-shivering Non-shivering thermogenesis thermogenesis aridarid brown brown adipose adipose tissue,tissue,
in Lindberg 0. (ed): Brown Adipose Tissue. London, Elsevier, I197O,pp26—42. 97O,pp26—42.
Burton V., Mitchell H. K., Young P., Petersen N. S.: Heat shock protection against cold stress of Drosophila melanogaster. Mo! 1988. CellBiol8:3550—3552, CellBiol8: 3550—3552, 1988. Foster D. 0.: Quantitative role of brown adipose tissue in thermo-
genesis, in Trayhurn Trayhurn P., P., Nicholls NichollsD. D.G. G.(eds): (eds) Brown Brown Adipose Adipose Tissue. London, Edward EdwardArnold, Arnold,1986, 1986,pp pp31 31—52. —52. Glaser F. M., Whittow G. C.: Retention in a warm environment of adaptation to localized localized cooling. cooling. JPhysiol JPhysiol 136: 136:98—111, 98—111, 1957. 6 Glaser Glaser E. M., Griffin J. P.: Effect of the cerebral cortex on habituaJPhysiol(London) tion. JPhysiol (London) 160:429—433, 160:429—433, 1962. Hammel H. T., Hildes J. A., Jackson D. C., Anderson H. T.: Ther-
mal and metabolic responses of the Kalahari bushmen to mod8
erate cold exposure at night. Tech. Rept. no. 62—44 Artic Med Lab, Ladd AFbase, 1962. LaddAFbase, and thermogenesis thermogenesis LeBlanc J.: Factors affecting cold acclimation and
inman.MedSciSportsExer20: Sl93—S196, 1988. inman.MedSciSportsExer20:S193—S196, LeBlanc J.: Stress and interstress adaptation. Federation Proc 28: 10
996—1101,1969. LeBlanc J.: Local adaptation to cold of Gaspé fishermen. J Appi Physioll7:950—953, 1962.
LeBlanc J.: Adaptation to cold in three hours. Am JPhysiol 212:
12 13
287— 294, 1966. 287—294,1966. LeBlanc J.: Man in the cold. Charles H. Thomas, 1975, pp 116— 126. LeBlanc J., Dulac C., Côté J., Girard B.: Autonomic nervous sysLeBlanc
tem and adaptation adaptation to to cold coldiii in man. man.JJAppiPhysiol Appi Physiol 39: 39: 181—186, 1975.
Downloaded by: University of Pennsylvania Libraries. Copyrighted material.
their hands in water varying between 0 and 10 °C, in order to removed removed the the fish fish from from the the nets nets when when these these are are pulled pulled into into the the boat. However they seldom experience shivering since they are are well well dressed dressed and and sufficiently sufficiently active. active. As As aa result result they they have have become become habituated habituated to to cold cold but but gave gave no no evidence evidence of of metabolic metabolic adaptation. adaptation. The The same same is is true true for for Eskimos Eskimos who who have have developed developed a socio-cultural adaptation and as a result of proper clothing and and shelters they did not develop metabolic adaptation adaptation but but bebecame habituated to cold. Habituation to cold reduces the mental disturbing effect of this stress and by reducing sympathetic activity it improves peripheral circulation and diminishes the strain on the cardiovascular system. As a result the habituated person is able to function more efficiently in the cold while being able to better resist cold injury through an improved cutaneous blood flow.
J. LeBlanc LeBlanc
S172 Int.J.SportsMed. Int.JSportsMed. 13(1992)
6 17
LeBlanc J., J., Robinson D., Sharman D. F., Rousignant P.: CateCate-
cholamines and short-term adaptation to cold in mice. Am JPhys-
8 18
19
20 20
2!
io1213: 1419—1423,1967. Leduc J.: Catecholamine production and release in exposure and
acclimation to cold. Ada PhysiolScand 53:(suppl) (suppl)183, 183,1961. 1961. cold.ActaPhysiolScand53: Mizzen L. A., Welch Welch W. W. J.: J.: Characterization Characterization of of the the thermotolerant thermotolerant L.A., cell.JCellBiollO6: 1105—1116,1988. Rennie Rennie D. W., Covino B. G., Honell B. J., Song S. H., Hong S. K.: Physical insulation of Korean diving women. J App! Physiol 17: 96 1—966,1962. 961—966,1962. Moseley P. P. L.: L.: Synthesis Synthesis of of 70K 70Kstress stress Ryan A. J., Gisolfi C. V., Moseley protein in human leucocytes: leucocytes: effect effect of of exercise exercise in inthe theheat. heat.JJApp! Appi Physiol70:466—471, 1991.
22
Scholander Scholander P. F., Hammel H. T., Hart J. S., Lemesurier D. H.,
Steen J.: Cold adaptation Physiol adaptation in in Australian Australian aborigines. aborigines.JAppI JAppiPhysiol 23 23
24 24
13:211—218, 1958. 1958.
Von Euler U. S.: Adrenal modullary secretion in NeuroenVon docrinology. Vol. II. Martini L., Ganong W. F. Academic Press, New York, York, 1967. New 1967. Young A. J., Muza S. R., Sawka M. N., Gonzalez R. R., Pandolf K.
B.: Human thermoregulatory responses to cold air are altered by repeated cold water immersion. J App! Appi Physiol 60: 1542—1548, 1986.
Jacques LeBlanc LeBlanc Department of Physiology Faculty of Medicine Laval University City, G Gl1K K 7P4 Quebec City, Canada Canada
The Different Types of General Cold Adaptation in Man J. Bittel Centre de Recherches du Service de Sante des Armees, Unite de Thermophysiologie et de Bioénergétique et Environnement, La Tronche Cedex, France
Abstract
J. Bittel, The Different Types of General Cold Adaptation in Man. Tnt J Sports Med, Vol 13, Suppi 1, ppSl72—S176, 1992.
Different types of general cold adaptation have been described over the last 50 years. Metabolic adaptation (Alacaluf Indians, Arctic Indians Eskimos), insula-
tive adaptation (coastal Aborigines of tropical northern Australia), hypothermic adaptation (bushmen of the Kalahari desert, Peruvian Indians) and insulative hypothermic adaptation (Central Australian Aborigines, nomadic Lapps, Korean and Japanese diving women). These different types of cold adaptation are related to the intensity of the cold stress and to individual factors such as diet, the
Introduction "Man in the cold is not necessarily a cold man"
(Leblanc, 23). In fact, relatively few humans exhibit cold Tnt. J. SportsMed. 13(1992)S172.—S176
GeorgThieme Verlag Stuttgart New York
level of physical fitness and body fat content. Thus, in natural environments, man develops a strategy of adaptation to
cold, which takes into account environmental and individual factors. This strategy is susceptible to be modified when these conditions change. Caloric intake deficit could have been responsible for the hypothermic adaptation observed after J.-L. Etienne's journey to the North Pole. Physiological responses were adapted to maintain an acceptable level of energetic reserves with a moderate hypothermia, which was not life threatening for the climatic conditions encountered by the polar explorer. Key words
Cold, adaptation to cold, thermoregulation
adaptation because there are many cultural and/or behavioral strategies such as migration, protective clothing, fire, modern life in well heated houses which reduce or suppress the environmental cold stress to which humans are exposed. In fact, without these different strategies, man should stay in tropical or subtropical countries.
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'
LeBlanc J., Hildes J. A., Héroux 0.: Tolerance of Gaspé fishermen to cold water. JAppiPhysiol 15: 1031—1034, 1960. LeBlanc J., Lafrance L., Villemaire A., Roberge C., Valliéres Vallières J., Rousseau S.: Catecholamines and cold adaptation. Fed Proc Bioenergelics, pp71—79,1971. —79,1971. energetics,pp7l LeBlanc J., Pouliot M.: Importance of noradrenaline in cold adaptation.AmJPhysiol2O7: 853—856,1964.
Mechanisms of Adaptation to Cold J. LeBlanc Department of Physiology, Faculty of Medicine, Laval University, Quebec City, GIK 7P4, Canada
Adaptation to Cold in Rats J. LeBlanc, Mechanisms of Adaptation to Cold. Tnt mt j. Cold. J. Sports Med, Vol 13, Suppl 1, pp S169—S172,
Most of the studies on the rat were done by placing placing them them at at 55 °C °C for for aa few few weeks. weeks. At At first first marked marked increases increases
in both adrenaline and noradrenaline are observed, adrenal
1992.
cortex is stimulated the animal loses weight and shivers; it is really a very stressing situation. After a few days the animals stop
The animal model used the most frequently for understanding the mechanisms of adaptation to cold in humans has been the rat. It has been established that rats kept in the cold for a few weeks stop shivering while preserving a normal internal temperature because of an enhanced thermogenic capacity of the brown adipose tissue (BAT) mediated by the sympathetic nervous system. Studies on groups of humans exposed to cold have shown that shivering is also attenuated but without compensatory increased in heat production possibly because of non-significant contribution of the BAT. However when humans and laboratory animals are exposed repeatedly to short severe
shivering, they eat more and body weight increases. At the
cold evidence for adaptation has been described. This adaptation is not metabolic; instead it is related to the phenomenon of habituation. When exposed to a novel stress such as cold, the alarm reaction is initiated as evidenced by the activation of the sympathetic nervous system which opposes the stressing situation. However with time, when it is realized that the normal functioning of the body is not endangered the responses are attenuated and enhanced tolerance is observed. This type type of of adaptation adaptation was was observed observedin in Eskimos, fishermen, outdoor workers, etc. Key words
Cold, adaptation, habituation, shivering
Introduction
It is often customary when you do clinical or applied research to look for an animal model. This has been the case for people working on adaptation to cold in humans. The animal which has been used for many years and by a large number of investigators is the rat. In a sense this choice made sense. It is true that the rat produces and loses much more heat per unit of body mass than than humans. humans. However However when when the the inincrease in heat production production due due to to cold cold is is expressed expressed as as aapercentpercentage of the resting metabolic rate, the response is comparable for both species; at 5 °C both rats and humans increase their
oxygen consumption by about 100% and both are comfortable when the room temperature is about 25 °C (8). On that basis both species may be used as models for one another. lnt.J.SportsMed. 13(1992)S169—S172 13(l992)S169—S172 New York GeorgThieme Verlag Stuttgart StuttgartNew
same time adrenaline in the blood which reflects the emotional component of the stress gradually declines. On the other hand plasma noradrenaline remains elevated as long as the animal is kept in the cold (18). The enhanced secretion of this kept this hormone, hormone, which reflects the activity of the sympathetic nervous system,
proved to be important in the processes of cold adaptation since the mere daily injections of noradrenaline for a few weeks to rats kept at room temperature, was sufficient to signif-
icantly improve cold tolerance in these animals which had never been exposed to cold before (15, 16). These findings found their explanation in studies on brown adipose tissue and which kept many scientists busy for many years. Essentially it has been shown that when exposed to cold rats become more tolerant because of a sustained stimulation of this tissue by the sympathetic nervous system. Indeed the BAT becomes highly thermogenic to the extent that the animals can remain in the cold without shivering (4). This is really an efficient adaptive tive process because shivering shivering isis not not aavery veryefficient efficientway wayofofproproducing ducing heat and besides that, it is an unpleasant and and disturbing disturbing experience.
Adaptation to Cold in Humans (Moderate Cold Exposure) Is the rat a good model for humans? In the fifties a few researchers, and I was one of them, started looking for populations who were living in a cold environment. Expeditions were organized for the Arctic, Antarctic, Australia and the Kalahari desert. It was found that Australian aborigenes, Kalahari bushmen or soldiers exposed to an Arctic environment during the winter, shivered less than subjects living 'iving in a temperate climate when exposed to a standard cold test (7, 12, 20, 22). These populations were more comfortable and were 20, 22). able to sleep without shivering the same as the rat. However humans and its model the rat, achieved the same aim aim but but by by
different strategies. In the rat shivering is replaced by non shivering thermogenesis which originates in the brown adipose tissue. Humans adapted to cold shiver less upon expo-
sure to a standard test and their heat production is reduced; they do not compensate by non-shivering thermogenesis. As a result there is a slight fall in deep body temperature which did not prove detrimental in the circumstances under which the experiments were done.
Downloaded by: University of Pennsylvania Libraries. Copyrighted material.
Abstract
5170 mt. J. Sports Med. 13(1992)
Does that mean that there is no brown fat in humans and that it cannot be switched on by exposure to cold? There is evidence for active brown fat in newborn humans and in people with pheochrornocytorna. pheochromocytorna. In normal adults the evidence is very thin if not lacking. It is possibly because humans are not exposed to low temperatures for sufficiently long period of time to activate the brown fat. Taken together the re-
suits sults obtained on rats and humans may indicate that we are dealing with different mechanisms for the induction of BAT and for the reduction of shivering found in cold adaptation. Indeed in humans there is no evidence of non-shivering thermogenesis due to BAT activation, yet as was observed in Aborigines they stop shivering in the cold.
b) Role of habituation
It has been suggested that the diminution of shivering and of discomfort are due to habituation, that is to a
centrally controlled negative reflex conditioning (6, 12). It seems as if the organism, when exposed to moderate cold for varying periods of time, learns that the situation is not dangerous and that the discomfort of shivering is really not necessary. In other words our system can differentiate between the emi-
nence of a catastrophe and the occurrence of a mere inconvenience and unconsciously reacts accordingly. This phenomenon has been called habituation. There is yet another possi-
bility of explaining at least in the rat, the disappearance of shivering when the animal is adapted to cold. Brflck Brück has has shown shown
that the elevation of temperature in the vicinity of the spinal cord specially at the level of the interscapular brown fat prevents the activation of spinal cord cold receptors and abolishes shivering (2). In other words as adaptation progresses, the BAT starts producing more heat and this would prevent shivering by blocking the spinal cord cold receptor stimulation. Adaptation to Cold (Severe Cold Exposure)
a) Human studies I would like now to raise the following question: What happens when human subjects or rats are exposed to more severe cold? Is habituation sufficient and is adaptation to cold still possible? Let us compare an experiment done
on humans exposed repeatedly to cold and another one on rats. Young and collaborators studied (on 7 male subjects) the effects of water immersion (18 °C) for 1.5 hour per day, 5 days a week during 5 weeks (24). Before and after the end of the experiment the responses of the subjects to a cold air air exposure exposure
(5 °C) were measured. The measurements included inc]uded oxygen consumption, rectal and skin temperature, and plasma catecholamine determinations. The results show that the increase in oxygen consumption and the intensity of shivering upon cold air exposure are the same before as they are after the repeated cold water immersion in spite of a significantly larger increase in plasma norepinephrine during the last cold water immersion as compared to the first one. This finding suggests that the repeated activation of the sympathetic nervous system failed to induce non-shivering non-shivering thern-iogenesis thermogenesis in in these these subjects. subjects.
These findings do not argue in favor of the brown adipose tissue tissue participation participation in in humans. humans. These These results results also also show show that that the the subjects are as much disturbed by the stress, if not more, after repeated water immersion since the norepinephrine secretion is higher during the last exposure than in the first one. Habitua-
tion is not evident. However this study gives additional information. mation. At At the the end end of of the the experiment experiment when when the the subjects subjects are are exexposed to a standard cold test, both the skin and deep body temperatures are lower than at the beginning of the experiment.
One would expect, with lower skin temperature and comparable heat production, a higher rectal temperature in the adapted subjects. Since the rectal temperature is actually lower, one has to conclude conclude that that the the equation equation for for heat heat balance balance has changed. The authors rightly suggest a change in heat distribution function at at aa higher higher tribution whereby the muscle mass would function temperature. However the advantage of such changes in heat distribution is not obvious since the capacity to generate heat is
not modified at the end of the experiment in spite of higher plasma norepinephrine levels.
Rats studies Comparable studies were done on rats which were exposed to cold air (— 5 °C), two hours per day for one month (1). The increase increase in oxygen consumption caused by this (I). The exposure is similar to that reported in humans when immersed in water at 18 °C; in both situations the increase is about 100% above resting values. At the end of the adaptation period, the brown adipose tissue mass increased by 50%, while a 2.5 fold
increase in the protein and DNA contents were measured. Contrary to what is found in humans, non-shivering thermogenesis develops in rats exposed to short repeated exposure to cold and their resistance to this stress is significantly improved. Adaptation to Cold (Short Severe Exposures)
a) Human studies There is another type of cold exposure which causes very little metabolic responses. It is the one produced by short local exposure to cold conditions. These are observed in regions where temperatures fall below zero in the winter and with varying wind velocity. If a person is well dressed and is somewhat active there will be no extra heat required to resist cold and for that reason adaptive metabolic responses should not be expected. However this person may encounter various degrees of cold discomfort since it is sometimes difficult to adequately protect the face and the extremities. When this occurs discomfort is experienced and the sympathetic nervous system is activated as evidenced by the elevation of plasma cate-
cholamines and the cardiovascular responses such as increased heart rate, blood pressure and peripheral resistance. In many of these situations adaptation to cold has been been obobserved and it has been described as habituation. Many groups have been studied such as students, soldiers, Eskomos, Gaspé fishermen, etc. (13). A standardized test for measuring the response to local cold exposure has been the so-called cold pressor test which consists in immersing the hand into cold water for a few minutes.
An example of this type of adaptation was ob-
served in Gaspé fishermen (10, 14). When their hands are placed in cold water, they experienced very little discomfort and a small rise in blood pressure. However these same subjects when tested for metabolic adaptation by exposure to a 10 °C temperature for one hour shivered even more than control subjects and their average skin temperature was higher. These findings are likely explained by the fact that Gaspé fishermen in the traditional way way of of fishing fishing repeatedly repeatedly immersed immersed
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a) Role of brown adipose tissue
J. LeBlanc
mt. J. Sports Med.13 13(1992) (1992) S171 S171 Int.J.SportsMed
Mechanisms ofAdaptation to Cold
Animal studies Similar studies were done on laboratory animals and the results obtained clearly differentiate between habituation and metabolic adaptation to cold (11, 17). Mice or
rats were exposed for 10 minutes to temperatures as low as — day 20 °C at hourly intervals for a total of 9 exposures per day —20 during during two two consecutive consecutive days. days. On On the the third third day day their their tolerance tolerance to cold was tested by measuring the fall in rectal temperature or the the survival survival at at low low temperatures. temperatures. Tolerance Tolerance to to cold cold was was signifisignificantly improved in animals repeatedly exposed for short periods to very low temperatures. temperatures. The The response response to to norepinephrine norepinephrine which is greatly increased in rats adapted by continuous exposure (3—4 weeks) to moderate cold (5 °C), because of enhanced thermogenic capacity of the BAT, was found to be the same in
control and habituated rats. What causes the improved cold tolerance of habituated animals? In 1957 Glaser and co-workers followed the heart rate increase when the tails of rats are placed in cold water (4 °C) daily for 10 days (5). They reported a gradual decline in the cardiac response. However they found that rats with frontal cortical lesions failed to adapt to the same exposures. The authors concluded to a central control for this
type of adaptation. We also found significant changes in the responses of the autonomic autonomic nervous nervous system. system. During During the thecold cold resistance test a 4-fold increase in epinephrine excretion was found in control animals, but the values for the habituated rats were within normal range (11). Similar findings were reported in humans when exposed many times to a centrifugation test. However with repeated parachute jumping epinephrine excretion remained high and von Euler concluded from these findings that habituation does not take place if an element of real real danger danger persists persists (23). (23). Since Since the the emotional emotional component component of of aa stress is reflected by an increased secretion of epinephrine, it is suggested that with habituation this component is gradually reduced. It is not known how this response could improve cold tolerance. It is interesting to note that habituation to stresses which do not depend on the heat producing capacity of the animals, has also been described. Rats placed at high altitude (30,000 feet) for 10 minutes, 9 times per day for 2 days were also shown to be much more resistant to hypoxia than control animals (9). These various studies suggest that upon exposure to a novel stress with which we are not familiar and not knowing whether it will be harmful or not, defence mechanisms such as as the the increased increased activity activity of of the the sympathetic sympathetic nervous nervous syssyssuch tem are activated. The amplitude of this response may be exaggerated at first and for that reason it may even be detrimental. But when it is realized after many exposures that the stress will
not cause damage to the organism, the responses are attenuated and improved tolerance i.e. adaptation is observed.
Adaptation to Cold and the Heat Stress Proteins
There is another area of research, recently developed which may have some implication in the process of
cold adaptation. Mammalian cells have been shown to become very tolerant to thermal damage when they are previously conditioned to high temperatures (41 °C) for short periods. There is now much evidence suggesting that certain proteins, particularly the 70 kDA, are involved in this process of improved resistance. These proteins have been termed the heat shock proteins (HSP). However since the HSP response has also been observed with many agents such as ethanol, inhibitors of mitochondrial function or viral infections it is suggested that these proteins be referred to as the stress protein. The synthesis of HSP is a non-specific stress response since it has been observed observed not not only only with with heat heat but but also also with with many many stress stress includinclud-
ing hypoxia. Furthermore the increased resistance to hypothermia in Drosophila which had been previously exposed to heat (3) suggests an interstress resistance which is possibly related related to to HSP HSP synthesis. synthesis. The The lethal lethal effect effect of of stress stress has has been been atattributed to the synthesis of HSP. Hoever there is some evidence showing that this protein is involved in the regulation of its own synthesis (19). As a result exposure to heat stress for ex-
ample increases 70K stress protein but the synthesis of this protein would be significantly reduced during a subsequent exposure to heat (21). Similar studies with cold stress have not
been reported but it would be interesting to see if previous lowering of tissue temperature temperature would would subsequently subsequently improve improve their tolerance to cold. References
2
Exercise during intermittent intermittent cold cold exposure exposure Arnold J., Richard D.: D.: Exercise prevents acclimation to cold rats. J Physiol 390:45—54, 1987. Brück K.: K.: Non-shivering Non-shivering thermogenesis thermogenesis aridarid brown brown adipose adipose tissue,tissue,
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Burton V., Mitchell H. K., Young P., Petersen N. S.: Heat shock protection against cold stress of Drosophila melanogaster. Mo! 1988. CellBiol8:3550—3552, CellBiol8: 3550—3552, 1988. Foster D. 0.: Quantitative role of brown adipose tissue in thermo-
genesis, in Trayhurn Trayhurn P., P., Nicholls NichollsD. D.G. G.(eds): (eds) Brown Brown Adipose Adipose Tissue. London, Edward EdwardArnold, Arnold,1986, 1986,pp pp31 31—52. —52. Glaser F. M., Whittow G. C.: Retention in a warm environment of adaptation to localized localized cooling. cooling. JPhysiol JPhysiol 136: 136:98—111, 98—111, 1957. 6 Glaser Glaser E. M., Griffin J. P.: Effect of the cerebral cortex on habituaJPhysiol(London) tion. JPhysiol (London) 160:429—433, 160:429—433, 1962. Hammel H. T., Hildes J. A., Jackson D. C., Anderson H. T.: Ther-
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their hands in water varying between 0 and 10 °C, in order to removed removed the the fish fish from from the the nets nets when when these these are are pulled pulled into into the the boat. However they seldom experience shivering since they are are well well dressed dressed and and sufficiently sufficiently active. active. As As aa result result they they have have become become habituated habituated to to cold cold but but gave gave no no evidence evidence of of metabolic metabolic adaptation. adaptation. The The same same is is true true for for Eskimos Eskimos who who have have developed developed a socio-cultural adaptation and as a result of proper clothing and and shelters they did not develop metabolic adaptation adaptation but but bebecame habituated to cold. Habituation to cold reduces the mental disturbing effect of this stress and by reducing sympathetic activity it improves peripheral circulation and diminishes the strain on the cardiovascular system. As a result the habituated person is able to function more efficiently in the cold while being able to better resist cold injury through an improved cutaneous blood flow.
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Jacques LeBlanc LeBlanc Department of Physiology Faculty of Medicine Laval University City, G Gl1K K 7P4 Quebec City, Canada Canada
The Different Types of General Cold Adaptation in Man J. Bittel Centre de Recherches du Service de Sante des Armees, Unite de Thermophysiologie et de Bioénergétique et Environnement, La Tronche Cedex, France
Abstract
J. Bittel, The Different Types of General Cold Adaptation in Man. Tnt J Sports Med, Vol 13, Suppi 1, ppSl72—S176, 1992.
Different types of general cold adaptation have been described over the last 50 years. Metabolic adaptation (Alacaluf Indians, Arctic Indians Eskimos), insula-
tive adaptation (coastal Aborigines of tropical northern Australia), hypothermic adaptation (bushmen of the Kalahari desert, Peruvian Indians) and insulative hypothermic adaptation (Central Australian Aborigines, nomadic Lapps, Korean and Japanese diving women). These different types of cold adaptation are related to the intensity of the cold stress and to individual factors such as diet, the
Introduction "Man in the cold is not necessarily a cold man"
(Leblanc, 23). In fact, relatively few humans exhibit cold Tnt. J. SportsMed. 13(1992)S172.—S176
GeorgThieme Verlag Stuttgart New York
level of physical fitness and body fat content. Thus, in natural environments, man develops a strategy of adaptation to
cold, which takes into account environmental and individual factors. This strategy is susceptible to be modified when these conditions change. Caloric intake deficit could have been responsible for the hypothermic adaptation observed after J.-L. Etienne's journey to the North Pole. Physiological responses were adapted to maintain an acceptable level of energetic reserves with a moderate hypothermia, which was not life threatening for the climatic conditions encountered by the polar explorer. Key words
Cold, adaptation to cold, thermoregulation
adaptation because there are many cultural and/or behavioral strategies such as migration, protective clothing, fire, modern life in well heated houses which reduce or suppress the environmental cold stress to which humans are exposed. In fact, without these different strategies, man should stay in tropical or subtropical countries.
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'
LeBlanc J., Hildes J. A., Héroux 0.: Tolerance of Gaspé fishermen to cold water. JAppiPhysiol 15: 1031—1034, 1960. LeBlanc J., Lafrance L., Villemaire A., Roberge C., Valliéres Vallières J., Rousseau S.: Catecholamines and cold adaptation. Fed Proc Bioenergelics, pp71—79,1971. —79,1971. energetics,pp7l LeBlanc J., Pouliot M.: Importance of noradrenaline in cold adaptation.AmJPhysiol2O7: 853—856,1964.
