Male, Long-Evans hooded rats were instrumented for monitoring core and hypothalamic temperatures as well as shivering and nonshivering thermogenesis in response to decreased ambient temperature in order to characterize the nature of the neural controller of temperature in rats at 1G and evaluate chronic implantation techniques for the monitoring of appropriate parameters at hypergravic fields. The thermoregulatory responses of cold-exposed rats at 2G were compared to those at 1G. A computer model was developed to simulate the thermoregulatory system in the rat. Observations at 1 and 2G were extended to acceleration fields of 1.5, 3.0 and 4.0G and the computer model was modified for application to altered gravity conditions. Changes in the acceleration field resulted in inadequate heat generation rather than increased heat loss. Acceleration appears to impair the ability of the neurocontroller to appropriately integrate input signals for body temperature maintenance

Horowitz, J. M.

Horwitz, B. A.

English

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FINAL TECHNICAL REPORT: NASA Grant #NGR 05-004-099
TITLE: EFFECT OF ALTERED GRAVITY ON TEMPERATURE REGULATION IN MAMkLS
[Investigation of Gravicy Effect on Temperature Regulation in Mammals]
PRINCIPAL INVESTIGATORS: B. A. Horvitz
J. M. Horowitz
INSTITUTION:	 University of California
Department of Animal Physiology
Davis, California 95616
PERIOD COVERED BY REPORT: November 1973 - July 1977
CONTENTS:
Page
I. General Objectives . 	 .	 .	 .	 .	 .	 .	 .	 .	 .	 .	 . .	 .	 .	 .	 .	 .	 .	 .	 . .	 .	 1
II. Procedures Followed . 	 .	 .	 .	 .	 .	 .	 .	 .	 .	 . .	 .	 .	 .	 .	 .	 .	 .	 . .	 .	 1
III. Nature of Neural Controller . . . . . 	 . . .	 .	 .	 .	 .	 .	 .	 .	 . .	 .	 1
A.	 Summary of Results .	 .	 .	 .	 .	 .	 .	 .	 .	 . .	 .	 .	 .	 .	 .	 .	 .	 . .	 .	 1
B.	 Conclusion.	 .	 .	 .	 .	 .	 .	 .	 . .	 .	 .	 .	 .	 .	 . 1
IV. Thermoregulatory Responses at 2G vs 1G . . .	 .	 .	 .	 .	 .	 .	 .	 . .	 .	 2	 -
A.	 Summary of Results . 	 .	 .	 .	 . .	 .	 .	 .	 . .	 .	 .	 .	 .	 .	 .	 .	 . .	 .	 2
B.	 Conclusions	 .	 .	 .	 .	 .	 .	 .	 .	 .	 .	 .	 .	 . .	 .	 .	 .	 .	 .	 .	 .	 . .	 .	 3
V. Extension of 2G Results to Other G Fields .	 .	 .	 .	 .	 .	 .	 .	 . .	 .	 3
A.	 Summary of Results .	 .	 .	 .	 .	 .	 .	 .	 .	 . .	 .	 .	 .	 .	 .	 .	 .	 . .	 .	 3
B.	 Conclusions	 .	 .	 .	 .	 .	 .	 .	 .	 .	 .	 .	 .	 . .	 .	 .	 .	 .	 .	 .	 .	 . .	 .	 4
VI. Final Remarks	 .	 .	 .	 .	 .	 .	 .	 .	 .	 .	 .	 .	 .	 . .	 .	 .	 .	 .	 .	 . .	 .	 4
VII. Publications Crediting Grant. . . . . 	 . . .	 .,,;. 4
t•,r
VIII. Appendix Items
i(Reprints of Recent Papers) a
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rNGR 05-004-099
I. GENERAL. OBJECTIVES OF THE PROJECT
The aim of this grant was to determine how well the mammalian thermoregulatory
system regulates under the combined stressors of altered gravity and ambient temper-
ature. Specifically, the grant proposed to compare the dynamic as well as static
characteristics of the thermoregulatory system at hypergravity and at 1G.
II. PROCEDURES THAT WERE FOLLOWED IN PURSUIT OF PROJECT OBJECTIVES
The work performed on this grant during the 2.5 years of its funding was
divided into several phases. The initial work involved characterizing the nature
of the neural controller of temperature in rats at 1G and evaluating chronic
implantation techniques for the monitoring of appropriate parameters at hypergravic
fields. This initial stage was followed by a period in which we compared the
thermoregulatory responses of cold-exposed rats at 2G to those at 1G and formulated
a computer model able to simulate the thermoregulatory system in the rat. The final
phase of the study involved an extension of our observations at 1 and 2G to acceler-
ation fields of 1.5, 3.0 and 4.OG and the modification of the computer model for
application to altered gravity conditions.
III. PHASE I -- Ground-based data regarding the nature of the neural controller
of temperature in rats.
A. Summary of Results. Male, Long-Evans hooded rats were chronically implanted
with internal electromyographic (EKG) leads, thermistors, and ground wires so that
shivering activity and a variety of temperatures could be monitored. In addition,
during the experiment concurrent noninvasive measurements of oxygen consumption
and core temperature were obtained. Thus the rats were instrumented for monitoring
core and hypothalamic temperatures as well as shivering and nonshivering thermo-
genesis in response to decreased ambient temperature. The results of these studies
provide ground-based information on the dynamic characteristics of the thermoregu-
latory controller at 1G, information relevant for interpreting space-flight data.
Among the results obtained are the following:
1. Chronic implantation of the thermosensors (hypothalamus, spinal cord,
core) and EKG electrodes had no apparent effect on the ability of the
rat to respond appropriately to cold exposure at 1G.
2. Changes in temperature of spinal cord receptors influenced shivering
with no effect on nonshivering thermogenesis.
3. Changes in hypothalamic temperature influenced nonshivering heat
production with no apparent effect on shivering.
4. Hippocampal theta rhythms were evoked upon thermal stimulation of the
animal (in these experiments, rabbits were utilized).
B. Conclusions Drawn
1. Signals from three major thermoreceptor locations in the rat (skin,
spinal cord, hypothalamus) do not apperc to be integrated in an
identical manner by the neural controllers for shivering and non-
shivering heat production at 1G. That is, sorting at the level
of the neural controllers seems to occur.
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NGR 05-004-099
2. The hippocampus appears to be involved in the mammal's response to
cold ambient temperatures -- most likely serving to elicit thermo-
regulatory behavioral responses (as opposed to the heat generating
responses evoked by the hypothalamus).
IV. PHASE II -- Comparison of the thermoregulatory responses of rats exposed
to cold at 2G versus those at 1G.
A. Summary of Results. Using the 4.5 ft. radius centrifuge at U.C. Davis,
rats were exposed to 2G fields for periods up to 7 hours. Some of these
rats were maintained at room temperature under controlled laboratory
conditions (Group A); others were cold acclimated (Group B) under con-
trolled conditions; a third group (C) was housed for 1 week in a relatively
stressful environment involving elevated and intermittent noise, continuous
light, and varying ambient temperatures (15-26'C); and the fourth group (D)
was maintained ("acclimated") for 3 weeks in the relatively stressful environ-
ment of Group C. The findings from this part of the project include those
listed below.
1. Upon initial exposure of all rat groups, thew occurred a rapid
decrease in colonic temperature, confirming earlier observations
of others.
2. This decrease was followed, after about 1 hour, by a slow recovery
toward precentrifugation levels, again confirming earliez studies.
3. The initial decrease in colonic temperature was accompanied by
decreased hypothalamic and spinal cord temperatures and increased
tail temperatures.
4. This initial decrease in colonic temperature was attenuated by
inverting the rat during centrifugation.
5. The magnitude of this initial colonic temperature decrease was
similar for all rat groups.
6. The dynamic characteristics of the thermoregulatory system were
examined by cold exposing the rats for 1 hour while they continued
to be centrifuged. This exposure to cold concurrent with centrifuga-
tion evoked further decreases in colonic temperatures that were not
accompanied by increased tail temperatures.
7. Within the first 7 hours of centrifugation (the maximum time period
used in the study) there was no effect of the time of onset of the
cold exposure on the magnitude of the temperature decrease.
8. The magnitude of this cold-induced fall in colonic temperature in
rats subjected to 2G fields varied in the four animal groups.	 !
Specifically, the magnitude of the decrease at ?.,G was less in those	 ?'
groups already acclimated to a stressful environment than in those
that were not so acclimated [i.e., Group B (cold-acclimated) vs. Group
A (noncold-acclimated); Group D (acclimated to adverse environment) vs.
Group C].
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NGR 05-004-099
B. Conclusions Drawn
1. The initial fall in temperature occurring with exposure to 2G may be
secondary to an effect on the cardiovascular system, as indicated by
the increase in tail temperature. That is, this latter change suggests
the shunting of warm blood to the tail with increased heat loss to
the environment, a response that would not be considered "normal" in
terms of thermoregulation. Thus, the response may represent a primary
alteration of the cardiovascular system that secondarily affects the
thermal responses of the rat.
2. In contrast, the observation that cold-exposed rats at 2G exhibit
a decreased ability to maintain colonic temperature appears to
reflect an altered ability to generate heat rather than an increased
heat loss (since no increases in tail temperatures were seen).
3. The prior state of the animal has a decided effect on its ability
to thermoregulate when exposed to cold at 2G.
^^. PHASE III — Extension of 2G olservations to other hypergravic fields and
computer simulation of the system.
A. Summary of Results. These experiments were conducted to determine if the
altered ability of rats to maintain colonic temperatures when challenged
with a 1 hour period of cold at 2G is proportional to the magnitude of the
acceleration field; and if the magnitude of the decreased thermoregulatory
ability is related to the onset time of the cold relative to that of accel- 	 / I
eration. Instrumented rats were placed on the 4.5 ft. radius centrifuge
and exposed to 1, 2, 3, or 4G for 5-7 hours. The 1 hour of cold exposure
began 0-3 hours after initiation of centrifugation. The following results
were obtained:
1. Whereas 1 hour of cold exposure at 1G caused only a slight decrease
in core temperature, 1 hour of cold exposure at hypergravic condi-
tions evoked significant falls in core temperature.
2. The magnitude of the cold-induced temperature drop varied directly
with the amplitude of the step changes in gravitational field. In
fact, the relationship seems linear and can be expressed by the
following equation:
Change in colonic temperature - 2.36G - 0.79 for 1-4G fields
3. No increases in tail temperature accompanied the cold-induced falls
in colonic temperature.
4. Delaying the time of onset of the cold exposure with respect to the
onset of the change in gravitational. field did not appear to
significantly affect the magnitude cf the cold-induced fall in
colonic temperature.
5. These data were used to formulate a computer simulation, using CSI',
with inclusion of gravity-dependent parameters.
3
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NGR 05-004-099
B. Conclusions Drawn
1. The thermoregulatory system appears to be affected :U mediately after
changes in acceleration field.
2. This effect involves inadequate heat generation rather than increased
heat loss.
3. The fact that cold induces a decrease in colonic temperature beyond
that occurring initially with the onset of acceleration implies that
the effect of hypergravity on the thermoregulatory system is not
simply an alteration of the set point. Rather, acceleration appears
to impair the ability of the neurocontroller to appropriately integrate
input signals for body temperature maintenance.
VI. FINAL MARKS
Work is 7-ontinuing on the effects of gravity on the thermoregulatory system
of mammals and is being supported in part by NASA grant NSG 2234 entitled,
"Thermoregulation in Rats: Effects of Hypergravity and of Norepinephrine."
VII. PUBLICATIONS ACKNOWLEDGING NASA SUPPORT
A. Full Papers
1. Flaim, L. K., J. M. Horowitz and B. A. Horwitz. 1976. Functional and
anatomical characteristics of the nerve-brown adipose tissue interaction
in the rat. PflOgers Arch. 365:9-14.
2. Flaim, K. E., B. A. Horwitz, and J. M. Horowitz. 1977. Coupling of signals
to brown fat: a- and 0-adrenergic responses in rats. Am. J. Physiol. 232:
R101-8109.
*3. Fuller, C. A., J. M. Horowitz, and B. A. Horwitz. 1975. Sorting of
signals from thermosensitive areas. Comput. Prog. in Biomed. 4:263-273.
*4. Fuller, C. A., J. M. Horowitz, and B. A. Horwitz. 1977. Spinal cord
thermosensitivity and sorting of neural signals in cold-exposed rats.
J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 42 : 154-158.
*5. Fuller, C. A., J. M. Horowitz, and B. A. Horwitz. 1977. Effects of
acceleration on thermoregulatory responses of unanesthetized rats. J.
Appl. Physiol.: Respirat. Environ. Exercise Physiol. 42(1):74-79.
*6. Fuller, r. A., B. A. Horwitz, and J. M. Horowitz. 1975. Shivering and
nonshivering thermogenic responses of cold-exposed rats to hypothalamic
warming. Am. J. Physiol. 228:1519-1524.
*7. Horowitz, J. M. 1975. Neural models an temperature regulation for cold-
stressed animals. In: Temperature Regulation and Drug Action, ed.
P. Lomax, E. Schoubsum, and J. Jacob. New York: Karger, pp. 1-10.
*8. Horowitz, J. M. 1976. Concurrent neural control of shivering and non-
shivering thermogenesis. Israel J. Mad. Sci. 12:1082-1085.
F
NGR 05-004-099
*9. Horowitz, J. M., C. A. Fuller, and B. A. Horwitz. 1976. Central neural
pathways and the control of nonshivering thermogenesis. In: Regulation
of DeRressed Metabolism and Thermogenesis, ed. L. Jansky and X. J. Musacchia,
Springfield: C. C. Thomas, pp. 3-25.
*10. Horowitz, J. M. and B. A. Horwitz. 19.8. Thermoregulatory responses of
unanesthetized rats exposed to gravitational fields of 1 to 4g. In:
COSPAR: Life Sciences and Space Research RVI, 0. by R. Holmquist and
A. C. Strickland. New York: Pergamon Press, pp. 77-82.
*11. Horowitz, J. M., B. A. Horwitz, and J. W. B. Mates. 1976. Thermoregulatory
models and their relationship to fever and neural transmitters. Biometeorology.
Wart II):137-149.
12. Horowitz, J. M. and J. W. B. Mates. 1975. Signal dispersion within a
hippocampal neural network. Comput. Biol. Med. 5:283-296.
*13. Horowitz, J. M., M. A. Saleh, and R. D. Karem. 1974. Correlation of the
hippocampal theta rhythm with changes in cutaneous temperature. Am.
J. Physiol. 227:635-642.
14. Horowitz, J. M., P. J. Smietana, and T. J. Willey. 1975. Dispersion along
fiber tracts and in the coupling between tracts and a cortical network.
Comput. Prog. in Biomed. 4:253-262.
15. Horowitz, J. M., R. G. Tearc:e, and B. Mulloney. 1976. Comparison of
electrical activity an y` behavioral correlates of neural networks in the
cat and locust. Comput. Prog. in Biomed. 6:92-100.
16. Horwitz, B. A. 1975. Physiological and biochemical characteristics of
adrenergic receptors and pathways in brown adipocytes. In: Temperature
Regulation and Drug Action, ed. P. Lomax, E. Schftbrum, and J. Jacob.
New York: Karger, pp. 150-158.
17. Horwitz, B. A. 1975. Pathways underlying non-shivering thermogenesis in
peripheral tissues. In: Depressed Metabolism and Cold Thermogenesis, ed.
by L. Jansky. Prague: Charles raiv., pp. 127-132.
18. Horwitz, B. A. 1976. Role of active sodium transport in brown fat
thermogenesis. Israel J. Mad. Sci. 12:1086-1089.
19. Horwitz, B. A. 1977. Adrenergic receptor involvement in brown adipose
tissue activation. In: Drugs, Biogenic Amines and Body Temperature, ed.
by P. Lomax, E. Schtfnbaum, and K. Cooper. New York: Karger, pp. 160-166.
20. Horwitz, B. A. and G. E. Hanes. 1976. Propranolol and pyrogen effects on
shivering and nonshivering thermogenesis. Am. J. Phyaiol. 230:637-642.
5
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NGR 05-005-099
21. i`.ates, J. and J. M. Horowitz. 1976. Instability in a hippocampal neural
network. Comput. Prog. in Biamed. 6:74-84.
B. Abstracts
*1. Fuller, C. A. Sorting of neural signals in the thermoregulatory control
of cold-exposed rats. Fed. Proc. 34:478, 1975.
2. Horwitz, B. A. 1975. Effects of a- and 8-adrenergic agonists on responses
of brown adipocytes. Fed. Proc. 34(2):477.
*3. Horwitz, B. A. and J. M. Horowitz. Thermoregulatory responses of
unanesthetized rats exposed to 1 to 4 G. Fed. Proc. 36:579, 1977.
4i
t
*Publications reporting research substantially supported by NASA 05-004-•099.
All other publications report work that made use of at least one equipment
item acquired (for other purposes) on NASA funds and thus NASA support
was acknowledged in the publication.	 t
ii	 y	 1	 t


Effect of altered gravity on temperature regulation in mammals: Investigation of gravity effect on temperature regulation in mammals

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