Transient peripheral warming accompanies the hypoxic metabolic response in the golden-mantled ground squirrel
Department of Zoology, University of British Columbia, Vancouver, BC, Canada, V6T 1Z4
* Author for correspondence at present address: Department of Biological Sciences, Brock University, St Catherines, ON, Canada L25 3A1 (e-mail: gtatters{at}brocku.ca)
Accepted 1 October 2002
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Summary |
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Key words: hypoxia-induced hypothermia, body temperature regulation, infrared thermography, regulated heat loss, metabolic depression, golden-mantled ground squirrel
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Introduction |
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The lowered metabolism and body temperature seen in hypoxia (i.e.
hypoxia-induced hypothermia; Wood and
Gonzales, 1996) are believed to reflect a regulated lowering of
body temperature set-point, affecting all thermoeffectors in a coordinated
manner. The alternative hypothesis that Tb merely falls as
a passive consequence of oxygen lack has been suggested as a possibility
(Fewell et al., 1997
;
Gordon, 1997
;
Mortola and Gautier, 1995
),
but there is little supportive evidence for this. The role of heat loss and
peripheral blood flow regulation during hypoxia, however, has not received
much attention in this context. In order for an endotherm to lower body
temperature, body heat must be lost from the core. This requires that
perfusion to the peripheral tissues be maintained or increased, to deliver
core heat to the periphery and thus more rapidly facilitate conductive,
convective and radiative heat transfer. This effector arm for body temperature
regulation will produce temporal changes in surface temperature
(Ts), depending on the deviation of Tb
from the regulated set-point. The Ts of a mammal, however,
depends on the interactions between ambient temperature
(Ta), metabolic heat production, insulation and cutaneous
blood flow (Klir et al., 1990
;
Webb et al., 1992
). Although
fur forms an insulative barrier to heat exchange, changes in blood flow
through the cutaneous arteriovenous anastamoses and the capillary beds
are still instrumental in regulating body temperature and heat loss
(Jänig, 1990
),
particularly within the thermoneutral zone (TNZ). For the most part, the body
surfaces that play the most significant role in regulating heat loss in
mammals (i.e. feet, ears and nose) are covered in relatively short fur
(Klir and Heath, 1994
) and
blood flow to these `thermal windows' is regulated by a hypothalamic
integrator.
Hypoxia can act on the regulation of cutaneous blood flow and
Ts in two ways: locally and centrally. Local effects can
result from the oxygen-limited metabolism of the smooth muscle of arterioles,
through the release of metabolically derived vasodilatory substances. Central
effects are integrated in the hypothalamus, and are mediated through the
sympathetic nervous system acting on the blood vessels themselves, effecting
either vasodilation or vasoconstriction
(Klir and Heath, 1994;
Marshall, 1998
). Cutaneous
blood flow, and thus Ts and heat loss, are mainly under
central sympathetic nervous control
(Jänig, 1990
), while
local factors play a small role under normal conditions. If, however, oxygen
demand is to be lowered to match the restricted oxygen supply in hypoxia, one
would expect the reductions in Tb and metabolic rate to be
accompanied by changes in blood flow that would favour essential tissues (such
as heart and brain) at the expense of less essential tissues (such as skin,
viscera and muscle; Sidi et al.,
1988
). If heat dumping occurs as a part of a regulated reduction
in Tb during hypoxia, however, this would require that
peripheral blood flow to the thermal windows be maintained or increased for
heat loss, rather than restricted to conserve oxygen for essential tissues, at
least during the early stages of hypoxic exposure. Given these potentially
conflicting demands, the aim of the current study was to demonstrate whether
peripheral heat dumping occurred during the early period of hypoxia exposure,
which would give strong support to the prevailing hypothesis that hypoxia
resets body temperature to a new and lower set-point, and would indicate that
controlled heat loss at the periphery must play an important role in this
process. To determine whether this is so, we measured Ts
at ambient temperatures well below (10°C), near the lower critical
temperature (22°C), and near the upper critical temperature (30°C) of
the TNZ of the golden-mantled ground squirrel
(Barros et al., 2001
), also to
test the hypothesis that the temperatures at which animals can make
thermoregulatory related cardiovascular adjustments (i.e. at the lower
critical temperature) would be associated with the largest, most prolonged
changes in Ts in hypoxia.
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Materials and methods |
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Metabolic rate determination
Metabolic rates were determined using flow-through respirometry. Squirrels
were placed in 0.5 1 Plexiglass chambers with incurrent gas flow set to 1500
ml min-1. Gases (21% O2 or 7% O2) were mixed
using a gas mixing flow meter (Cameron GF-3/MP). A subsample (150 ml
min-1) of the excurrent gas from the respirometer was scrubbed of
water vapour and CO2 and analysed for O2 content
(Beckman OM-11 Oxygen analyser), while another subsample of gas was scrubbed
of water vapour and analysed for CO2 content (Beckman LB-2
CO2 analyser).
O2 and
CO2 were
subsequently calculated using equations from Withers
(1977
), and the respiratory
exchange ratio (RER) was determined as
CO2/
O2.
Infrared imaging and surface temperature estimation
One technique for assessing peripheral heat loss and
Ts, particularly in endotherms, is infrared thermography.
This optical technique involves detecting electromagnetic radiation (at
wavelengths in the range 8-12 µm), and converting the intensity of this
radiation to a greyscale or colour image in the visible range of light. All
objects above 0K emit infrared radiation (IR), and the intensity of this
radiation is related to the Ts and the emissivity of the
body (Speakman and Ward,
1998). This technique has found many diagnostic uses in clinical
and veterinary applications where a rapid assessment of limb and peripheral
blood flow is desired (Inagaki et al.,
1992
; Jones, 1998
;
Turner, 2001
).
In the present study, surface temperatures were estimated using an InframetricsTM thermal imaging camera (Model 522 Imaging Radiometer). In order to obtain accurate surface temperatures and still maintain a sealed respirometer, we experimented with a number of thin, plastic materials that would serve as `windows' through which the animal's IR could pass to the camera. Polyethylene (a Ziploc© freezer bag stretched onto a hard plastic frame) provided an adequate seal for the respirometer while permitting most IR to pass. We were able to validate the accuracy of the IR estimates through the polyethylene by using materials of known temperature and emissivity. The video output from the thermal imaging camera was recorded on videotape and transferred to a computer using a frame-grabber card (Grab-It ProTM). Grey-scale pictures (256 colours) from the camera were captured at 1 min intervals to provide a redundant number of images for off-line analysis. Subsequently, the grey-scale images were analysed using SigmaScanTM software. Outlines of the eyes, ears, nose, feet and back (flank region) were drawn using the software trace function, and then the average intensity (based on a 0-255 scale) of the enclosed area was calculated and converted to the corresponding surface temperature. Surface temperatures were determined from images every 5 min (see Fig. 1 for a sample image and setup). When the squirrels changed position, so that parts of their bodies became invisible to the camera, the best estimate of surface temperature was determined from other captured images within 2 min of the desired time point.
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Experimental protocol
Squirrels were placed into the respirometer, which was then placed within a
temperature controlled environmental chamber. The animal was allowed to
acclimate to the experimental setup for at least 1 h. Ambient temperature was
kept at one of three different temperatures, 10°C (N=7), 22°C
(N=7) and 30°C (N=7). Metabolic rate and whole body
thermograms from the thermal imaging camera were initially recorded every
minute for 140 min. After 20 min of recording normoxic baseline values, the
oxygen in the respirometer was changed to 7% O2 for the subsequent
60 min, after which the respirometer was returned to 21% O2 and 60
min of recovery from hypoxia was recorded.
Data analysis
After determining Ts, we calculated the difference
between Ts and Ta
(Tsa) at each part of the body to
approximate the effect of ambient temperature on regional cutaneous blood
flow. We also determined the change in Ts above normoxic,
control values at each surface (
Ts=hypoxic
Tsnormoxic Ts) and at each
temperature, as an estimate of the temporal changes in blood flow occurring
during hypoxia. For purposes of analysis, Ts,
Tsa,
Ts,
O2,
CO2 and RER were
averaged over 5 min intervals and expressed as means ± S.E.M. All
statistics relating to the infrared thermography were actually performed on
the raw Ts data. Variables were analysed using a
repeated-measures analysis of variance (ANOVA), with temperature as the factor
and time as the repeated measure. Post hoc multiple comparisons were
made using a Bonferroni test compared against a normoxic, control value at the
appropriate temperature. All statistical tests were considered significant at
P<0.05.
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Results |
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Effects of Hypoxia and Recovery
Upon exposure to 7% O2,
O2 and
CO2 decreased
significantly below normoxic levels at 10°C and 22°C, but did not
decline significantly at 30°C (Table
1; Fig. 2). Stable
values were usually achieved by 40 min of hypoxic exposure at all
temperatures. Neither
O2 nor
CO2 were
significantly affected by Ta during hypoxia. The RER
increased significantly during the first 10 min of hypoxia at all
temperatures, and returned to normoxic levels within 40 min.
Upon returning the respirometer gas to normoxia,
O2 and
CO2 increased
significantly within the first 10-15 min at both 10°C and 22°C
(Table 1;
Fig. 2). These large increases
in
O2 and
CO2 accompanied
bouts of intense shivering. At 30°C,
O2 and
CO2 decreased
significantly on return to normoxia, remaining lower than control values for
up to 20 min. RER was not significantly affected by normoxic recovery at
10°C and 22°C, although it was transiently lower during recovery at
30°C.
Surface temperatures
Effects of ambient temperature in normoxia
The surface temperatures of all parts of the body were significantly
affected by Ta (Table
2), being lowest at 10°C and highest at 30°C. However,
Tsa was highest at 10°C and lowest at
30°C (Fig. 3A), such that a
significant linear correlation existed between
Tsa and Ta at each
surface of the body except for the nose, where the
Tsa at 30°C was lower than expected and
thus the relationship between
Tsa and
Ta at the nose was not linear. In general the
Tsa was similar for all surfaces except the
eyes where this difference was much higher.
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Effects of hypoxia and recovery
Ts, Ta and
Ts all changed significantly during hypoxia. At
10°C, the Ts of the nose and feet increased
significantly during the first 15 min of hypoxia, whereas the
Ts of the eyes and the flank did not. Both of the latter
surfaces, as well as the ears, then displayed significant decreases in
Ts,
Tsa and
Ts during the last half of the exposure to hypoxia
(Table 2; Fig. 4).
|
At 22°C, the Ts of the nose, ears and feet increased significantly and this increase was sustained for nearly 30 min in hypoxia, whereas the eyes and the flank showed no changes at any time in hypoxia (Figs 4, 5). In some cases, squirrels adopted a heat loss posture, lying with their feet elevated above their bodies (Fig. 5). At 30°C, there were small, but significant increases in Ts in the nose and feet during the first 15 min of hypoxia, but no changes in other body surfaces throughout hypoxia.
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On recovery from hypoxia, there was little temporal change in the Ts at most body surfaces and at most Ta values, except for the Ts of the flank and the eyes. At a Ta of 10°C, the Ts of the flank was significantly lower than that seen during the normoxic control period after 10 min of normoxic recovery. This effect, however, was short-lived. At 22°C, the Ts values of all surfaces during recovery were not significantly different from normoxic control values. At 30°C, there was a prolonged and significant decrease in the Ts of the eyes, which lasted well into the recovery period.
Since Tsa and
Ts (Fig.
6) are calculated from Ts itself, the
significant differences in Ts are reflected in these other
variables.
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Discussion |
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Critique of methods
IR thermography has not seen much experimental application in the study of
temporal changes in blood flow. Although it is a useful, non-invasive way to
assess surface temperature, it suffers from several disadvantages: (1) the
surface of interest must always be available for viewing, (2) the emissivity
of the object must be known accurately, and (3) in animals with an insulating
layer, the technique only assesses surface temperature and not the actual skin
temperature. We feel that we were able to overcome these drawbacks in the
present study and that the data we obtained provide a good indication of skin
temperature and, hence, useful insight into peripheral blood flow to the
various surfaces. We were able to obtain sufficient images of each body
surface of interest in each animal throughout each experiment. The emissivity
of fur is quite high (Speakman and Ward,
1998) and should not have changed throughout an experiment, making
the calculated values of Ts at each of these surfaces
relatively accurate. Finally, although Ts could only be
assessed at the outer layer of the fur, the nose, ears and feet have a short,
coarse fur covering, and thus our calculated values of Ts
for these surfaces should also be an accurate estimate of skin temperature. By
contrast, our calculated values of Ts for the flank, which
has longer fur and a larger degree of insulation, will be a less accurate
indication of flank skin temperature.
Given that our measures of changes in Ts accurately
reflect changes in skin temperature, the question then arises as to what
extent these changes can be assumed to reflect reflexly mediated changes in
blood flow. The major concern when using changes in surface temperature to
assess thermoregulatory control is the potential for local tissue hypoxia in
the cutaneous vascular bed to alter blood flow via non-reflex
mechanisms, and also to effect heat loss. We do not believe that this was
occurring in our squirrels for several reasons. (1) There were different
changes in Ts in response to hypoxia at different ambient
temperatures. This suggests that the changes were not just a passive effect of
local hypoxia acting on peripheral blood flow but were reflexly mediated and
proportional to the magnitude of the need to lose heat. (2) Non-specific
increases in local blood flow should occur at most, if not all, body surfaces,
and this was not the case. The feet, ears and nose increased in temperature
while the temperature of the surface of the flank and eyes either decreased or
remained constant. (3) Given that the haemoglobin oxygen affinity in this
species is very high, 7% O2 should only produce a small degree of
desaturation of arterial blood (Maginniss
and Milsom, 1994), which should not lead to local hypoxia severe
enough to prompt significant humorally mediated increases in cutaneous blood
flow.
Thus, in the present study we measured Ts, from which we inferred changes in Tskin, from which we inferred changes in peripheral blood flow. We then use the latter to assess the extent to which changes in peripheral blood flow and heat transfer to the environment during hypoxia can provide an insight into whether the reductions in Tb are the result of a regulated or a passive process.
Hypoxic metabolic response
One of the most notable results of our study was the observation that the
lower the Ta and the higher the starting metabolic rate,
the greater the hypoxia-induced fall in metabolism. At the highest ambient
temperature (lowest starting metabolic rate), metabolic rate did not change
significantly in hypoxia, while at the lowest ambient temperature (highest
starting metabolic rate) metabolic rate fell dramatically to the lowest levels
recorded during hypoxia (Fig.
2). This strongly suggests that the decrease in metabolism seen in
hypoxia was due to the suppression of thermogenic heat production to basal
levels combined with a subsequent fall in metabolism due to the decrease in
Tb. Previous studies have shown that
Tb in hypoxia decreases in proportion to
Ta; colder ambient temperatures lead to lower
Tb values (Barros et
al., 2001; Wood and Stabenau,
1998
). This explanation suggests that
O2 did not fall
significantly in squirrels at 30°C because they were near the upper end of
(but within) the TNZ, where thermogenesis would already be basal, and the fall
in Tb would be small. Squirrels at 22°C were near the
lower end of (but below) the TNZ and displayed a small but significant
reduction in thermogenesis, a larger fall in Ta, and a
larger fall in metabolism. Squirrels at 10°C were well below the TNZ and
thus showed the largest fall in metabolism, due to the removal of a
significant thermogenesis, a larger fall in Tb and the
subsequent Q10 effects on metabolic rates (cf.
Barros et al., 2001
).
The kinetics of the post-hypoxic recovery of metabolic rate also support this view. At the lowest ambient temperature, the post-hypoxic metabolic rate showed a large overshoot before returning to pre-hypoxic levels. This probably reflects both the greater metabolic suppression in hypoxia and a more pronounced decline in Tb. Upon return to normoxia, the Tb set point immediately shifts back to normothermic levels and, given increased input from peripheral thermosensors associated with the lower ambient temperature, and increased input from deep body (hypothalamic and spinal) thermosensors due to the greater fall in Tb, provokes a large increase in thermogenesis (shivering, and possibly non-shivering), bringing Tb back to 38°C. In the squirrels held at 22°C, the post-hypoxic overshoot in metabolic rate was smaller although still significant, probably reflecting lower feedback from peripheral and deep body thermosensors, and less drive to increase thermogenesis.
At 30°C ambient temperature, not only was there no overshoot in
metabolic rate post-hypoxia, but
O2 and
CO2 were reduced
for 10-20 min. Frappell et al.
(1991
) also found that a
post-hypoxic metabolic suppression could be transiently present in kittens.
This result is somewhat perplexing but may reflect the shift of the TNZ to
lower temperatures during hypoxia that has been described by others
(Barros et al., 2001
;
Dupré et al., 1988
). If
the TNZ was lowered during hypoxia, 30°C may have been above the upper
critical temperature of the new TNZ. As a result, the steady state metabolic
rate at 30°C during hypoxia may have included costs associated with
maintaining a Tb below Ta. Upon
switching the inspired gas back to normoxia, these costs would disappear and
metabolic rate would be lowered transiently until the TNZ and
Tb returned to pre-hypoxic levels.
Hypoxia induced changes in Tb via regulated heat loss
During the early stages of hypoxia, the surface temperature of particular
body surfaces with minimal insulation warmed in a fashion that was ambient
temperature specific (Fig. 3B).
At 10°C and 22°C ambient temperature, the Ts of
the nose, ears and feet increased for the first 20-30 min in hypoxia, while at
30°C, the increases in Ts were small and confined to
the nose and feet (Table 2;
Figs 4,
6). These increases in surface
temperature occurred simultaneously with reductions in metabolic heat
production and at a time when Tb was known to be falling
(cf. Barros et al.,
2001). This suggests that core heat was being shifted to the
periphery, and is consistent with the hypothesis that this facilitates a
regulated drop in body temperature.
The kinetics and magnitude of the changes in Ts of the feet, ears and nose are also consistent with this hypothesis. Changes in Ts were of shorter duration at 10°C than at 22°C and smaller in magnitude at 30°C than at either of the other temperatures. Thermoregulatory control of Tb within the TNZ is predominantly mediated through changes in peripheral vasomotor tone. At or above the upper critical temperature, the periphery is already maximally vasodilated, and there is little room for more vasomotor thermoregulatory adjustments. At temperatures well below the lower critical temperature, peripheral changes in Ts occur rapidly as the greater temperature gradient from the animal to the environment allows for more rapid body cooling.
Although not specifically measured in this study, total heat loss in
hypoxia is predicted to increase in parallel with changes in surface
temperature. Previous studies have shown this in other species. Gordon
(1997) measured heat loss in
hypoxic rats with direct calorimetry, and demonstrated that heat loss
increased and remained elevated above heat production for nearly an hour in
hypoxia. Similar results were observed in a small primate breathing 10%
O2 (Tattersall et al.,
2002
), although the duration of elevated heat loss was shorter,
reflecting the more modest decrease in Tb in the primate
(only 2°C versus a 4-5°C drop in the rat). While it would be
possible for Tb to decline without an increase in heat
loss, provided metabolic rate (i.e. heat production) decreased, the decrease
in Tb would be a passive process and the speed with which
it fell would be much slower than that which would be observed if heat loss
were also increased.
There is also evidence from studies on other mammals to suggest that levels
of hypoxia similar to those used in the present study lead to neurally
mediated changes in cutaneous vascular resistance that can account for the
changes in peripheral blood flow and heat loss. Systemic hypoxia evoked a
reflex dilation of the saphenous (leg) vein in the dogs, a mechanism thought
to result from the withdrawal of sympathetic tone
(Britton, 1984). Similar
results were found in the ear of the rabbit
(Iriki and Kozawa, 1976
). While
neither study inferred a thermoregulatory role for this decreased cutaneous
sympathetic tone in hypoxia, these decreases in cutaneous sympathetic tone and
vascular resistance were accompanied by increases in sympathetic tonus and
resistance to other regions of the body (splenic, muscle), suggesting that the
opening up of cutaneous vascular beds is preferentially regulated in
hypoxia.
There is further indirect evidence to suggest that Ts
was being regulated for thermoregulatory purposes during hypoxia, including:
(1) some squirrels were observed to adopt apparent heat-loss postures, lying
with their feet above their bodies during hypoxia
(Fig. 5); and (2) the lack of
peripheral warming during the post-hypoxic period, despite the increased
metabolic rate (and hence, heat production) at 10 and 22°C. At this stage,
the squirrels were shivering intensely, and
O2 was 2-3 times
higher than pre-hypoxic levels, yet there was no apparent change in
Ts in any part of the body, suggesting that the heat was
being maintained within the core. In fact, Ts passively
warmed or did not change at all as the animals' body temperature and
metabolism returned to normal. This suggests that during normoxic recovery,
Ts was being controlled to conserve the heat being
produced by shivering muscles and brown adipose tissue to warm the squirrel
back to its normoxic Tb.
Conclusions and perspectives
There now exists a considerable amount of data to indirectly support the
hypothesis that moderate to severe levels of hypoxia lead to a controlled
decline in Tb. This hypothesis has been difficult to test
directly. The current study, however, adds to the indirect evidence by
demonstrating that changes in Ts, as a possible reflection
of changes in peripheral blood flow and heat loss, proceed in a coordinated
fashion that is consistent with a carefully regulated, hypoxia-induced decline
in Tb. While it remains to be shown quantitatively that
these changes in Ts do contribute to total heat loss, and
that this is indeed a reflexly mediated process, the changes in
Ts do appear to be differentially controlled in a manner
that is dependent upon ambient temperature, and consistent with the general
hypothesis.
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Acknowledgments |
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References |
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Barros, R. C., Zimmer, M. E., Branco, L. G. and Milsom, W.
K. (2001). Hypoxic metabolic response of the golden-mantled
ground squirrel. J. Appl. Physiol.
91, 603
-612.
Britton, S. L. (1984). Cutaneous venodilation in response to systemic hypoxemia in dogs. J. Surg. Res. 36, 9 -16.[Medline]
Dupré, R. K., Romero, A. M. and Wood, S. C. (1988). Thermoregulation and metabolism in hypoxic animals. In Oxygen Transfer from Atmosphere to Tissues (ed. N. C. Gonzalez and M. R. Fedde), pp. 347-351. New York: Plenum Press.
Fewell, J. E., Megirian, D. and Stobie-Hayes, K. M. (1997). Influence of carotid denervation on the body-core temperature and metabolic responses to changes in ambient temperature during normoxemia and acute hypoxemia in guinea pigs during postnatal maturation. Can. J. Physiol. Pharmacol. 75, 104 -111.[CrossRef][Medline]
Frappell, P., Lanthier, C., Baudinette, R. V. and Mortola, J.
P. (1992). Metabolism and ventilation in acute hypoxia: a
comparative analysis in small mammalian species. Am. J.
Physiol. 262, R1040
-R1046.
Frappell, P., Saiki, C. and Mortola, J. P. (1991). Metabolism during normoxia, hypoxia and recovery in the newborn kitten. Respir. Physiol. 86, 115 -124.[Medline]
Gordon, C. J. (1997). The role of behavioural thermoregulation as a thermoeffector during prolonged hypoxia in the rat. J. Thermal Biol. 22, 315 -324.
Inagaki, M., Ohno, K., Hisatome, I., Tanaka, Y. and Takeshita, K. (1992). Relative hypoxia of the extremities in Fabry disease. Brain Dev. 14, 328 -333.[Medline]
Iriki, M. and Kozawa, E. (1976). Patterns of differentiation in various sympathetic efferents induced by hypoxic and by central thermal stimulation in decerebrated rabbits. Pflugers Arch. 362, 101 -108.[Medline]
Jänig, W. (1990). Functions of the sympathetic innervation of the skin. In Central Regulation of Autonomic Functions (ed. A. D. Loewy and K. M. Spyer), pp. 390 . New York: Oxford University Press.
Jones, B. F. (1998). A reappraisal of the use of infrared thermal image analysis in medicine. IEEE Trans. Med. Imaging 17, 1019 -1027.[CrossRef][Medline]
Klir, J. J. and Heath, J. E. (1994). Thermoregulatory responses to thermal stimulation of the preoptic anterior hypothalamus in the red fox (Vulpes vulpes). Comp. Biochem. Physiol. A 109, 557 -566.
Klir, J. J., Heath, J. E. and Bennani, N. (1990). An infrared thermographic study of surface temperature in relation to external thermal stress in the Mongolian gerbil, Meriones unguiculatus. Comp. Biochem. Physiol. A 96, 141 -146.[Medline]
Maginniss, L. A. and Milsom, W. K. (1994). Effects of hibernation on blood oxygen transport in the golden-mantled ground squirrel. Resp. Physiol. 95, 195 -208.[CrossRef][Medline]
Marshall, J. M. (1998). Chemoreceptors and cardiovascular control in acute and chronic systemic hypoxia. Braz. J. Med. Biol. Res. 31, 863 -888.[Medline]
Mortola, J. P. (1993). Hypoxic hypometabolism
in mammals. News Physiol. Sci.
8, 79-82.
Mortola, J. P. and Feher, C. (1998). Hypoxia inhibits cold-induced huddling in rat pups. Respir. Physiol. 113, 213 -222.[CrossRef][Medline]
Mortola, J. P. and Gautier, H. (1995). Interaction between metabolism and ventilation: effects of respiratory gases and temperature. In Regulation of Breathing, Vol. 79, Lung Biology in Health and Disease (ed. C. Lenfant J. A. Dempsey and A. I. Pack), pp. 1011-1064. New York: Marcel Dekker, Inc.
Sidi, D., Teitel, D. F., Kuipers, J. R., Heymann, M. A. and Rudolph, A. M. (1988). Effect of beta-adrenergic receptor blockade on responses to acute hypoxemia in lambs. Pediatr. Res. 23, 229 -234.[Abstract]
Speakman, J. R. and Ward, S. (1998). Infrared thermography: principles and applications. Zoology 101, 224 -232.
Tattersall, G. J., Blank, J. L. and Wood, S. C.
(2002). Ventilatory and metabolic responses to hypoxia in the
smallest simian primate, the pygmy marmoset. J. Appl.
Physiol. 92, 202
-210.
Turner, T. A. (2001). Diagnostic thermography. Vet. Clin. North Am. Equine Pract. 17, 95-113.[Medline]
Webb, P. I., Speakman, J. R. and Racey, P. A. (1992). The implications of small reductions in body temperature for radiative and convective heat loss in resting endothermic brown long-eared bats (Plecotus auritus). J. Thermal Biol. 18, 131 -135.
Withers, P. C. (1977). Measurement of
O2,
CO2, and
evaporative water loss with a flow-through mask. J. Appl.
Physiol. 42, 120
-123.
Wood, S. C. and Gonzales, R. (1996). Hypothermia in Hypoxic Animals: Mechanisms, Mediators, and Functional Significance. Comp. Biochem. Physiol. B 113, 37-43.[CrossRef][Medline]
Wood, S. C. and Stabenau, E. K. (1998). Effect of gender on thermoregulation and survival of hypoxic rats. Clin. Exp. Pharmacol. Physiol. 25, 155 -158.[Medline]
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