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Departments of 1 Physiology and Biophysics, 2 Physical Therapy, Exercise Science and Nutrition, and 3 Neurology, State University of New York at Buffalo, Buffalo, New York 14214
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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When rats, acclimated to an ambient temperature (Ta) of 29°C, are exposed to 10% O2 for 63 h, the circadian rhythms of body temperature (Tb) and level of activity (La) are abolished, Tb falls to a hypothermic nadir followed by a climb to a hyperthermic peak, La remains depressed (Bishop B, Silva G, Krasney J, Salloum A, Roberts A, Nakano H, Shucard D, Rifkin D, and Farkas G. Am J Physiol Regulatory Integrative Comp Physiol 279: R1378-R1389, 2000), and overt brain pathology is detected (Krasney JA, Farkas G, Shucard DW, Salloum AC, Silva G, Roberts A, Rifkin D, Bishop B, and Rubio A. Soc Neurosci Abstr 25: 581, 1999). To determine the role of Ta in these hypoxic-induced responses, Tb and La data were detected by telemetry every 15 min for 48 h on air, followed by 63 h on 10% O2 from rats acclimated to 25 or 21°C. Magnitudes and rates of decline in Tb after onset of hypoxia were inversely proportional to Ta, whereas magnitudes and rates of Tb climb after the hypothermic nadir were directly proportional to Ta. No hyperthermia, so prominent at 29°C, occurred at 25 or 21°C. The hypoxic depression of La was least at 21°C and persisted throughout the hypoxia. In contrast, Ta was a strong determinant of the magnitudes and time courses of the initial fall and subsequent rise in Tb. We propose that the absence of hyperthermia at 21 and 25°C as well as a persisting hypothermia may protect the brain from overt pathology.
disrupters of circadian rhythms; effects of hypoxia; hypoxic depression of activity; level of activity
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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A WEALTH OF LITERATURE over the past century has revealed the physiological responses to hypoxia. It has been known since the 1930s that small animals drop their body temperature (Tb; see Ref. 6) and metabolism (10) during hypoxia. Over the intervening seven decades, a plethora of studies has been performed to test a variety of hypotheses to account for the mechanisms responsible for this hypoxic-induced hypothermia (1). Newborn mammals hyperventilate by reducing their metabolic rate, achieved by a regulated inhibition of all forms of thermogenesis (14). Most of the early investigators of this hypometabolic-hypothermic response to hypoxia studied rats that were subjected to short bouts of hypoxia lasting from a few minutes to a few hours. More recently, experimental paradigms have employed more prolonged hypoxic exposures up to 3 days (2) or a week (15). The results of the more prolonged hypoxic exposures confirmed that, with the introduction of 10% O2, the circadian rhythms of Tb and activity level (La) were totally disrupted, and the mean Tb fell significantly below its usual daytime nadir. After the expected hypothermia in animals acclimated to 29°C, the fall in Tb was reversed and climbed to a hyperthermic level (i.e., to a peak Tb significantly above the prehypoxic nocturnal peak; see Ref. 2). In addition, the Tb and La circadian rhythms of these 29°C-acclimated rats remained in total abeyance throughout the 63 h of hypoxia and reappeared only upon termination of the hypoxia (2). In the study in which the hypoxia was imposed for a week (15), the fall in Tb reversed and Tb climbed from its hypothermic nadir. However, this climb did not carry Tb above its prehypoxic nocturnal peak. The ambient temperature (Ta) to which the rats in this study were acclimated was not reported. We hypothesized that a difference in Ta might account for the discrepancy in the findings between the two studies. No information is available concerning the role Ta may play in governing the hypoxic-induced responses of Tb and La. This fact was a major impetus for the present study.
In a preliminary study (12), we acclimated groups of rats to 29, 25, or 21°C and compared the overt brain damage resulting from a 63-h exposure to 10% O2. Forty-eight hours after termination of the hypoxia, brain pathology was significantly greater in animals acclimated to 29°C than in those acclimated to 25 or 21°C. These results reinforced the need to answer the question: "What role, if any, does Ta play in the hypoxic-induced responses of Tb and La?" Because more brain damage was detected in the rats maintained at 29°C than in those at 25 or 21°C during the sustained hypoxia, we hypothesized that the magnitudes of the hypothermic and hyperthermic components of the hypoxic-induced responses might be influenced by the Ta. For example, if the hypothermic component was smaller and the hyperthermic component was larger at 29°C than at 25 or 21°C, these differences could well contribute to the greater brain damage at 29°C. Thus the objective of the present study was to determine the effect of Ta on the magnitude and time course of the changes in Tb and La during 63 h of 10% O2.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Animal Preparation and Protocols
Our methods have been described in detail previously (2). Mini Mitter probes with diameters of 10 mm were calibrated for temperature, sterilized, and surgically implanted aseptically in the abdomen of 32 adult Sprague-Dawley rats for continuous detection of Tb and La. Upon recovery from surgical anesthesia, each rat was placed in its own cage in a sound-proof, all-weather room. The temperature and lighting of the room were tightly controlled. For the two protocols used in the present experiments, the Ta was maintained at either 21 or 25°C. The automated lighting system switched from dark to light every 12 h (at 0600 and 1800) throughout the 159 h of each experimental protocol.After acclimation to the dark-light cycles and the selected Ta, the body weight was obtained from each animal before and after the 63-h exposure to hypoxia.
Instrumentation
A receiver for detecting the Tb and La signals from the implanted probes was placed under the cage of each rat. Hypoxic rats were placed in cages within an airtight large plastic chamber through which either room air or a 10% O2 in N2 gas mixture was delivered at a flow rate of 5 l/min, a rate at which the fraction of inspired CO2 did not rise above 1.0%. Control rats (n = 6) were placed in cages outside this plastic chamber also on top of a Mini Mitter receiver and breathed room air throughout the entire experiment. All rats were provided with food and water ad libitum, left untethered and unhandled (23), and for 7 days were acclimated to the desired Ta for 48 h before acquisition of baseline data. After acclimatization, the fraction of O2 in the hypoxic rat chambers (n = 8 at each Ta) was lowered to 10% by opening a nitrogen flood valve. When the percentage of O2 within the chamber approached the 10% level, preset valves were opened, and a continuous flow of the hypoxic mixture was delivered to the chamber for 63 h. This reduction in chamber gas to 10% O2 took ~35-40 min. Hypoxia was always initiated at 1800 when both Tb and La were rising toward the nocturnal peaks of their circadian cycles. At termination of the 63-h exposure to hypoxia, the gas valves were closed and the chamber was opened to room air. Hence, return to air breathing was essentially instantaneous.Data Acquisition
The temperature-specific frequency and the instantaneous position of each animal were acquired continuously throughout the 159 h of an experiment from the Mini Mitter probes. These data were relayed to a computer in an adjacent room through a multiplexer for reduction by a Windows-based software program (Vital View; Mini Mitter). This program converted the frequency of the probe to Tb. All recorded changes in Tb were expressed as degrees centigrade and tabulated every 15 min. Changes in an animal's position were converted to "counts per 15 min" as a measure of La. Both of these telemetry signals were converted to an ASCII file format and entered into the Microsoft Excel Workbook file format. Graphs of Tb and La were generated for each animal for the 159 h of each experiment.Data acquired for rats maintained at 29°C in an earlier study (2) are included in this study for comparison purposes.
Data Reduction
Mean Tb values were determined both in control rats not exposed to hypoxia and in the hypoxic rats before onset of hypoxia at each Ta. The hypoxic-induced response of Tb was arbitrarily divided into phases I, II, and III based on changes in Tb over the 63 h of hypoxia. Phase I of the hypoxic-induced responses of Tb was analyzed at each Ta for the magnitude of the diurnal decline (Tb in °C), rate of fall in Tb (dTb/dt in °C/h), and the duration of the Tb decline. Phase II was initiated at the start of the Tb climb from its nadir to the beginning of phase III, which was demarcated by a dramatic change in the rising slope of Tb and continued until the chamber was opened to air. Phases II and III of the hypoxic-induced responses of Tb were analyzed for the rates of change in Tb.The hypoxic-induced responses of La were assessed during each phase of the Tb hypoxic response by comparing counts per 15 min.
Because Tb and La data from individual rats at each Ta were similar, group data were pooled for analysis. Corresponding variables in the control rats and in the hypoxic rats during the three phases of the hypoxic-induced response were compared using the Student's t-test and accepting P < 0.001 as a statistically significant difference unless otherwise indicated.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Effects of Ta on Body Weight
Before hypoxia, the mean weight of all the rats was 392.2 ± 32.4 g. Each control rat gained weight over the 159 h of the experiment. Both the magnitude and the percent of the gain were inversely related to Ta as shown by data in Table 1. In contrast, over the same period of time, the hypoxic-exposed rats lost 10% of their body weight regardless of the Ta. The weight loss of the hypoxic group in absolute grams was greatest at 29°C and least at 21°C (Table 1).
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Effects of Ta on Tb
Phase I of the Tb response to hypoxia.
Before hypoxia, the differences among the means of Tb at
Ta values of 21, 25, and 29°C were not significantly
different. The 10% O2 was introduced in the rat's chamber
at a time when Tb was rising toward its nocturnal peak.
Tb immediately ceased climbing and instead declined over
the next hour or two toward a marked hypothermia (Fig.
1). This decline in Tb to the
nadir constituted phase I of the hypoxic-induced response
and occurred whether Ta was 21, 25, or 29°C (Fig. 1,
top, and Fig. 2). The
Tb at the nadir was significantly lower than the prehypoxic
Tb, regardless of the Ta. However, the
magnitude of the decline in phase I (i.e., the difference
between Tb at the onset of hypoxia and Tb at
the nadir) was dependent upon Ta. At 21°C the decline was
more than two times that at 25°C and more than fivefold that at
29°C. The duration of the hypoxic-induced hypothermia also depended
on Ta. At 21°C it was 1.1 h longer than at 25°C
and 2.2 h longer than at 29°C (Table
2 and Figs. 1 and 2). During phase
I, the rate of decline in Tb
(dTb/dt in °C/h) was fastest at 21°C and
slowest at 29°C. Of all the parameters of phase I, the
times required to reach the nadir (i.e., the duration of phase
I in Table 2) were least influenced by Ta (Fig. 2).
Nonetheless, except for the absolute Tb at the nadir, all
other phase I parameters of the hypoxic-induced response
were significantly less at 29°C than at 25 or at 21°C. At the
latter Ta, the hypothermia was most severe, the fall in
Tb was fastest, and the duration of the hypothermia was
longest when compared with the two higher Ta values (Table 2 and Figs. 1 and 2).
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Effects of Ta on Mean Tb
The mean Tb of control rats at 21 and 29°C was 37.5°C and 37.6 at 25°C (Fig. 3). The mean Tb in the hypoxic rats during the 63 h of exposure to hypoxia was very dependent on Ta. Compared with the controls at the same Ta, the means for Tb of the hypoxic rats at 21 and 25°C were significantly reduced (P < 0.001). At 29°C, the mean Tb of the hypoxic rats was actually 0.1°C above that of the controls, a difference with a P value <0.05.
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Phase II of the Hypoxic-Induced Response
The onset of phase II was marked by a progressive climb of Tb from its hypothermic nadir toward its prehypoxic mean (Fig. 1). Phase II of the hypoxic response was defined at each Ta as the interval between the termination of phase I and the time when the rising slope in Tb underwent a significant change (Fig. 1). The ultimate peak Tb achieved in phase II at 21°C was significantly lower than that at 25 or 29°C. As described previously (2), at a Ta of 29°C, Tb climbed well above its normal nocturnal peak. No hyperthermia occurred at 25 or 21°C (Fig. 1). Ta did not affect the rate at which Tb climbed during phase II (Fig. 1 and Table 3). The differences in the durations of phase II, although not identical across the three Ta values, were not statistically significant.
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Phase III of the Hypoxic-Induced Response
In phase III, the interval between the change in the rising slope of Tb and the termination of the hypoxia, Tb continued to climb throughout the remaining 36 h of phase III at a Ta of 21 or 25°C, but this rise was at a slower and more variable rate compared with that during phase II (Fig. 1). In contrast, as reported previously (2) when Ta was 29°C, Tb declined from its hyperthermic peak during phase III. At the end of phase III, when hypoxia was terminated, Tb was not different across the three Ta values and circadian rhythm of Tb was reestablished.Effects of Ta on the Mean La and on the Hypoxic-Induced Responses of La
La means at the three Ta values.
The mean La for control rats and the hypoxic rats at each
Ta is shown in Fig. 4. The
mean La values for both groups show wide variability at
each Ta. The mean La values for the control
rats at 21 and 25°C were not different. The mean La at
29°C was significantly lower than at the other Ta values.
The mean La values for the hypoxic groups decreased with
each increase in Ta. For example, the mean La
decreased from 39.5 to 30.5 and to 16.9 counts/15 min with
Ta increases from 21 to 25 and to 29°C, respectively.
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La during hypoxia at the three Ta values. La decreased in every rat with the introduction of 10% O2 and remained at a low level compared with its prehypoxic level throughout the hypoxia. During the hypothermia of the Tb response (i.e., phase I), the differences among La values across the three Ta values were not statistically significant. In other words, the initial hypoxic depression of La was independent of Ta.
21°C. At 21°C during phase I of Tb, La fell from a mean prehypoxic level of ~50 counts/15 min (100%) to <25 counts/15 min (i.e., a 40-50% decrease in counts) at its most depressed period. Toward the end of phase II, La gradually climbed toward its prehypoxic mean level. During phase III, La values were not different from their prehypoxic values, and the circadian rhythm of La had reappeared. In other words, at 21°C the effect of hypoxia on La was considerably less than when the rats were at 25 or 29°C.
25°C. At 25°C, with the onset of hypoxia, La declined over the first 6 h from 50 to ~15 counts/15 min. Although La remained depressed throughout phase II of the Tb response, low-level activity and low-level circadian oscillations in phase with the dark-light cycles gradually reappeared during phase III of the Tb response (Fig. 1). The magnitude of the cyclic activity (i.e., the full excursion of the cycle) was only 50% or less compared with that recorded in the prehypoxic period (Fig. 1).
The hypoxic-induced response of Tb at 29°C. As reported previously (2), within 7 h of the onset of hypoxia, activity counts decreased from ~50 to 7 counts/15 min (i.e., close to quiescence). During phases II and III of the hypoxic-induced response to Tb, La counts remained significantly lower than those during the prehypoxic period. After ~25 h (i.e., close to the onset of phase III of the Tb response), La increased somewhat but still remained suppressed compared with its prehypoxic level (Fig. 1). Throughout the entire 63 h of hypoxia at 29°C, La was essentially devoid of circadian rhythm.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Previous and New Findings Regarding Hypoxic Responses
The results of this study are an extension of our previous study (2) in which we reported for the first time that rats, acclimated to 29°C, had a delayed hyperthermia in response to a prolonged hypoxia. The early hypothermia at the onset of hypoxia confirmed previous findings reported by numerous investigators (4, 13-15, 20), but the delayed hyperthermia was a new finding, missed by others because their animals were exposed to bouts of hypoxia too short to reveal the full expression of the Tb hypoxic-induced response. The hypothermic component of the hypoxic response of Tb is thought to reflect a suppression of the thermal regulatory system (7), to be neuroprotective (3), and to override the thermogenesis generated by the hypoxia-induced increase in ventilation (20). The results of the current study have revealed that Ta is an important determinant of the magnitude and time course of the hypoxic-induced Tb response to a prolonged (63 h) hypoxia. The major new findings of this study are that rats, acclimated to 25 or 21°C, responded immediately to hypoxia with the expected decline in Tb that was followed by a progressive climb in Tb. However, unlike rats acclimated to 29°C, none of the rats acclimated to 25 or 21°C exhibited hyperthermia. The progressive rise in Tb never reached the prehypoxic nocturnal peak at any time during the exposure to hypoxia. Nonetheless, the fact that Tb climbed from its hypothermic nadir suggests that the thermoregulatory events that caused the hypothermia waned or were counteracted by competing events, or both. Another key finding was that Ta exerted differential affects on the Tb and La responses to hypoxia.Thermoregulation During Hypoxia
Adult rats are excellent thermoregulators, whereas newborn rats lack both well-developed thermoregulatory and locomotor abilities. For the hypoxic-induced hypothermia to occur, heat loss must exceed heat production. The major heat-loss mechanisms in rats are vasodilation of their feet and furless tails and an increased evaporative water loss produced by licking and grooming after applying saliva to their pelts (7). Behavioral thermoregulation is a major component of the rat's thermoregulatory armamentarium (8). When the environment provides a thermal gradient, rats select a higher Ta when their Tb is low and vice versa, as if their thermal regulation were geared to reduce the circadian oscillations in Tb (18). Behavioral regulatory responses were not an option in the present study since the Ta was preselected and tightly controlled.For Tb to rise during phase II, heat conservation and heat production must have overcome or replaced heat- loss mechanisms. Heat production is qualitatively similar in animals acclimated to temperatures from 23 to 6°C (7). Among the major heat-production mechanisms are vasoconstriction and shivering. Hypoxia is a potent stimulus for the release of catecholamines, which provoke thermogenesis (11).
Role of Ta in the Hypoxic-Induced Response
A Ta of 29°C falls within a rat's thermal neutral zone (7). Hence, minimal values of heat production and heat loss are required to maintain a constant Tb. The thermal gradient between a Ta of 29°C and Tb is smaller than that at a Ta of 25 or 21° C and may be a limiting factor in the animal's ability to lose heat (5, 7, 9). Nonetheless, a Ta of 29°C is reputed to be optimal for the ventilatory, circulatory, thermoregulatory, metabolic, and other vital control centers. However, in comparison with 25 or 21°C, a Ta of 29°C may be devastating for homeostasis during hypoxia, as suggested by the characteristics of the hypoxic-induced Tb response. It has been claimed that the hypothermia in phase I of the hypoxic response is protective in that it overrides the thermogenesis generated by the hypoxic-induced increase in ventilation (20, 22). At 29°C the magnitude and duration of the phase I hypothermia are significantly less than at 25 or 21°C (Table 2 and Fig. 2). Furthermore, heat dissipation to the environment, whether by way of conductive, radiative, or convective heat exchange, is considerably less than would be the case at 25 or 21°C (21).In phase II of the 29°C response, Tb transiently climbed above the nocturnal peak Tb. This hyperthermic component of the hypoxic response is likely maladaptive and selectively deleterious to some neuronal populations. Subdural hematomas, intraventricular hemorrhages, and other signs of overt brain pathology were seen in posthypoxic 29°C brains but not in the 25 or 21°C brains that experienced no hyperthermia (12). The differences among the Tb responses to hypoxia and the existence of brain pathology seen at different Ta values revealed, for the first time, that Ta plays a critical role in determining 1) the profile of the hypoxic-induced Tb response, 2) the output of the thermoregulatory system, and 3) the pathological effects hypoxia exert on the brain.
Hypoxia Disrupts Circadian Control
The circadian rhythms of both Tb and La were totally disrupted at the onset of hypoxia in every rat at each Ta as if the circadian control system were totally inhibited. At 25 and 21°C, but not at 29°C, a very low level of Tb circadian cycling reappeared in phase III. Failure of the rhythm to reappear at 29°C suggests that at the warmer temperature some mechanisms were in play to sustain the circadian disruption.The circadian clock's location, neural composition, and molecular mechanisms underlying its rhythmicity have been elucidated at the molecular level in recent years (18, 19). Nonetheless, an understanding of the circadian clock's intracircuitry and the interconnections it makes with the thermoregulatory, ventilatory, cardiovascular, and physiological control systems remain to be elucidated. Perhaps then the Tb and La responses to hypoxia will be understood. Feedback circuits between the brain regions involved in thermal regulation and the suprachiasmic nucleus, the site of the biological clock's control center, remain to be identified.
Ta Modification of Hypoxic-Induced Responses of La
Onset of hypoxia, at a time when La was rising toward its normal nocturnal peak, caused La to reverse and undergo a progressive decline. This change in La did not just interrupt the circadian rhythm of La but abolished it (Fig. 1, bottom). The reduction in La was not secondary to the decline in Tb. It more likely was due to a specific centrally driven suppression of motor activity. By the time Tb had reached its hypothermic nadir (i.e., the onset of phase II), La was also at its lowest level regardless of the Ta. The depression of La was less severe and less enduring at 25 and 21°C than at 29°C. Before the termination of the prolonged hypoxia, the La circadian rhythm gradually reappeared at a low level when rats were at Ta values of 25 or 21°C but not when at 29°C.Other Potential Consequences of Hypoxia
Poncet et al. (17) have demonstrated that sustained hypoxia disrupts the circadian rhythms for central neurotransmitters. It remains to be determined whether the impact of hypoxia on the circadian rhythmicity of central neurotransmitters or hormones, such as melatonin, are as dependent on Ta as are the Tb and La rhythms.Summary and Conclusions
Regardless of Ta, the responses of Tb and motor activity to hypoxia were dramatic (2, 15, 16) and independent of one another. Hypoxic exposure completely disrupted the circadian rhythms of both Tb and La whether Ta was 21, 25, or 29°C.This study demonstrated that the depth to which Tb plunges upon exposure to hypoxia and the level to which it "recovers" or reverts toward its prehypoxic mean is critically dependent on Ta. It remains to be determined to what lower limit Tb could be driven during phase I of the hypoxic-induced response by lowering Ta below 21°C. The transitory nature of the hypoxic-induced hypothermia may maintain homeostasis until more slowly recruited adaptive mechanisms of ventilatory acclimation and increased arterial O2 capacity come into play to counter the continuing stresses imposed by hypoxia. The delayed reversal of Tb may signal a "recovery" of the circadian and thermal regulatory systems from the initial suppression or disruption imposed by the hypoxia.
The daily rhythms of Tb and La are independent of one another during normoxia (18). As revealed by this study, the hypoxic-induced responses of La and Tb are also independent of one another. Despite prolongation of hypoxia, La partially recovers at 21 and 25°C but remains depressed at 29°C when the animals are hyperthermic. It seems unlikely that hyperthermia contributes to the La depression.
Newborn infants display hypothermia during hypoxia, a putative cerebroprotective response (12). The observations reported in the present study are relevant to the question of defining the optimal Ta for management of infants in the setting of clinical hypoxia. Because the hypothermic response to hypoxia is inversely related to body mass, it seems less likely that exposure to hypoxia would elicit major alterations in the Tb of adult humans. Indeed, which circadian rhythms are affected by hypoxia in humans remains to be determined. Depression of La clearly occurs during hypoxia in adult humans (11). If hypoxia depresses the circadian rhythms of Tb and La and the metabolic rate then these responses may serve as early adaptive mechanisms to cope with hypoxia in adult humans and in rats.
Perspectives
Regardless of the Ta, Tb and La responses to hypoxia are dramatic (2, 15). The circadian rhythms of both Tb and La are completely disrupted for the duration of the hypoxia, and both Tb and La decrease to minimums below normal nadirs. It is unknown if the depth of the decline and the peak of the climb are potentially dependent on the Ta. The colder the air, the faster and deeper is the fall in Tb in rats. Simultaneously with this hypothermia, La is suppressed, reducing heat production and metabolic rate. Although these responses are putatively neuroprotective, the delayed facets of the Tb response, particularly at higher Ta values, appear to be destructive.| |
ACKNOWLEDGEMENTS |
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We thank Dr. David Megirian for enthusiastic encouragement and constructive criticisms throughout these experiments. We also thank Alex Salloum's organizational skills and contributions to the implementation of the experiments and the acquisition and reduction of the data. Last, we thank the reviewers who provided constructive criticisms and excellent guidance that helped us to improve the manuscript.
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FOOTNOTES |
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Address for reprint requests and other correspondence: B. Bishop, State Univ. of New York at Buffalo, Dept. of Physiology and Biophysics, Sherman Hall/South Campus, Buffalo, NY 14214 (E-mail: bpbishop{at}ACSU.buffalo.edu).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 5 June 2000; accepted in final form 5 December 2000.
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TOP
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METHODS
RESULTS
DISCUSSION
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 A. A. Romanovsky Do fever and anapyrexia exist? Analysis of set point-based definitions Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2004; 287(4): R992 - R995. [Abstract] [Full Text] [PDF]
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D. C. Holley, C. W. DeRoshia, M. M. Moran, and C. E. Wade Chronic centrifugation (hypergravity) disrupts the circadian system of the rat J Appl Physiol, September 1, 2003; 95(3): 1266 - 1278. [Abstract] [Full Text] [PDF]
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A. D. Ray, A. J. Roberts, S. D. Lee, G. A. Farkas, C. Michlin, D. I. Rifkin, P. T. Ostrow, and J. A. Krasney Exercise delays the hypoxic thermal response in rats J Appl Physiol, July 1, 2003; 95(1): 272 - 278. [Abstract] [Full Text] [PDF]
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H. Scholz Adaptational responses to hypoxia Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2002; 282(6): R1541 - R1543. [Full Text] [PDF]
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G. J. Tattersall, J. L. Blank, and S. C. Wood Ventilatory and metabolic responses to hypoxia in the smallest simian primate, the pygmy marmoset J Appl Physiol, January 1, 2002; 92(1): 202 - 210. [Abstract] [Full Text] [PDF]
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Significant difference from the
Tb at 21°C. +Significant difference from
Tb at 25°C.
