The range of daily fluctuations of the proportion of the amount of consumed water and its content in the body was evaluated by means of a water metabolism regulation factor. This index constitutes a relative measure of fluctuations of the constant of tritium water elimination from the body per 24 hours. It is established that under conditions of long term hypokinesia regulation of water metabolism is disturbed both in humans and in animals. Still more marked changes are observed 2 to 3 weeks after restoration of motor activity. The shifts noted are evidence of general biological regularity of disturbance of regulation systems in long term restriction of motor activity and in the early restoration period

Krotov, V. P.

English

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NASA TECHNICAL MEMORANDUM
	 NASA TM-76309
WATER METABOLIJ)M REGULATING MECHANISMS IN HYPOKINESIA
V. P. Krotov
(NASA-TN-7b309) `sATE& nG ABULISA REGULATING
	 N61-15b71
MECHANISMS IN HYPUKINE.SIA (National
Aeronautics and Space Adainistration) 4 p
HC A Ol/MF A01
	 CSCL its	 Unclas
G5/52 130J1
Translation of "Sostoyaniye regulyatornykh mekhanizmov vodno,%o obuena
pri gipokinezii," Patologicheskaya Fiziologiya i Ekspperimental'naya
Terapiya, No. 1, Jan-Feb 1980, pp. 15-18.
JA6 ^= 81
Na q
RECEIVED
  
AccasLf
NATIONAL AERONAUTICS AND SPACE ADMINISTRATION
WASHINGTON, D.C. 20546	 AUGUST 1980
STANDARD TOILE PAGE
NAS^AM " 16309
^• GavM+ A<t.•.IM ^:.. t R.e10iMt'• C.t•i.s N..
WA IM	 TABOLISM REGULATING IMCHANISMS s' A g eeST 1980
IN HYPOKINESIA f. ►eranw in. or.M,•o1,M Code
7. Aw4w4•1
V. P. Krotov
8. Performing OroMi.otion R•por1 No.
Institute of Medical-Mological Problem 10,	 rr.,11 (n11 N..
of the UBSR Ministry of Public Health
/, Podorn,ng ore.n, lotion Now,on
	 A^ro•e
Leo Kanner AssocUtee
••	 I No.
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	 qN/ onA P66941 Covororl
Translation
12. $Pon ing 	 goney Name and ANne•
NatN -	 Aeronattics and Space Adminis-
14. spo1u«.n, A..ne y
 c.r.tration s Washington, D.C. 20546
is. 5"01	 +«	 ote•
Trans^a eon of "Sostoyaniye regulyatornykh mekhanismov vod-
nogo obmens,ppri gipokinesiis" Patologi ¢hes" Fisiologiya i
1,	 1980 #	15Eksperimental 'naya Terapiya t No.	 Jan-Feb	 pp.	 -18.
to	 Ae.,..«
the amount of consumed water and its content in'the body was
evaluated by means of "water metabolism regulation factor"
suggested by the author. 	 This index constitutes a relative
measure of fluctuations of the constant of tritium water slim
ination from the body per 24 hours.	 It is established that
under conditions of long-term hypokinseia regulation of water
metabolism is disturbed both in humsos And in animals (doge).
Still more marked changes are observed 2-3 weeks after res-
toration of motor activity.	 The shifts noted are evidence
of general biological regularity of disturbance of regulation
systems in long-term restriction of motor activity and in'
the early restoratipn period.
17. K•y Mor1• (Selects Or Authorm) 11.	 01•k1but
	 So +	 .n+
This copyrighted Soviet work is
reproduced and sold by NTIS un-
der license from VAAP, the Sov-
iet copyright agency.	 No fur-
ther copying is permitted with-
11.	 sand ► 	 Cb••il. l•1 M I• r• or 1)y	 r 20.	 S•conry Cli••.	 .	 •	 1 •.	 ..
Unclassified Uf►classif ied 6
MATER METABOLISM REGULATING MECHANISMS IN HYPOKINESIA
V. P. Krotov
Institute of Medical-Biological :problems
USSR Ministry of Public Health, Moscow
Until recently water metabolism has been evaluated principally
on the basis of data of water consumption and diuresis, and the ratio
of these values even received the name "hydration coefficient of the
organism." However, in fact this index gives an extremely rough in-
dication of hydration, if only because about 50% of the total mois-
ture losses by the organism takes place by an extrarenal route.	 16
Only now is the extremely impua-tant integral index--the total fluid
content in the organism--beginning to be systematically studied in
clinics [1, 93 although it was determined in man as early as 1934 [13 .
Data not only of the hydration status of the organism but also of
the degree of the expression of Lts periodio fluotuatims are "tremely
significant for the evaluation of water metabolism. In normal living
conditions the quantity of water in the organism, being an integral
index that depends on the interaction of the nerve centers which reg-
ulate it, fluctuates daily within a definite range. The qualitative
evaluation of this range in the norm and also in hypokinesia was the
object of this investigation. For this purpose we daily examined the
dynamics of the alteration of the tritium water concentration in the
fluids of the organism, which is determined by the ratio of the quan-
tity of consumed water to its content in the organism and depends on
the nature of neuroendocrine regulation.
Procedure
The investigation was conducted on 6 }&*&&thy men and on 4
dogs in conditions of free motor activity and in hypokinesia.
During the time of bedrest (49 days) the subjects were not al-
um ers In the margin indicate pag nat on in the foreIgn text.
1
lowed to sit even to use the bedpan. Water consumption was
not limited. The motor activity of the dogs was limited by
a special fixing device that permitted the adoption of a "lying,"
"sitting." or "standing" position. After clinical examination
snd selection the animals were trained to stet in the fixing de-
vices. Water was given to them together with food (1 feeding per
day) at a rate of 95 ml per 1 kg of body weigh;.
The range of fluctuations of the hydration status of the
organism, which reflects the condition of the mechanisms that
participate in the maintenance o f an adequate level of water
metabolism, was evaluated on the basis of the water metabolism
regulation coefficient proposed by us. This index is a relative
measure of the fluctuation of the constant of tritium water
elimination from the organism every 24 hourst
RC	 (arbitrary units)
where RC is the regulation coeff icient t o^  is the average standard
deviation and \ is the average arithmetic constant of tritium
water elimination for every 24 hours.
The constant of the isotope elimination was determined by
the formula t
where At-1 , At is the activity of the isotope in the fluid phase
of the organism ( samples of blood, exhalation or urine) during the
next 24 hours and a is the base of natural logarithms.
For the execution of the indicated investigations tritium
water was injected intramuscularly or intravenously at the fal-
lowing ratest for humans- -about 100 mcC1 [5], for dogs --10 mcC1
per 1 kg of body weight. The resultant data were subjected to
variation statistical analysis on an M-220 computer.
Results and Discussion
2
In the process of the subjects' stay on bedrest (Fig. 1) the
vaine of the water metabolism regulation coefficient changed in a
wavelike manners after a significant increase in the first week of
hypokinesia (18% against the background s P < 0.01) it did not differ
reliably from the background value during the second and third weeks
of the experiment. Then (43rd-49th days) its value again grew (208%
against the background, P < 0.05). On restoration of motor activity
the value of this coefficient was increased to an even greater degree
and by the and of the observation period ( 15th and 23rd days) it ex-
ceeded the background level by 134% (P < 0.01).
In animals, ►unlike hum ­ c, I  the dyn-%mics of the coefficient was
studied in conditions of strictly dosed and constant water consumption.
Its value increased by 3.5-5.5 times va a result of limiting the motor
activity of dogs for 30 days (Fig. 2). During the 2 weeks of the res-
torative period the value of the water me-tsbolism regulation coeffic-
ient continued to exceed the background value by 3.8 to 4.2 times,
It is known that marked shifts in water metabolisms caused by its
transition to a lower equilibrium level, arise as a result of hypo-
kinesia [4, 8 9 12 1. We have already shown that on the resumption of
activity the total content of water in the organism reaches the back-
ground value by the 4th-8th day of the free regimon 13 0 61. But does
normalization of water metabolism as a whole occur with this?
A B
A B
C	 Fig. 1. Alteration of the water
metabolism regulation coefficient in a
person in hypokinesia.
j	 Here and in Fig. 2e A - backgrounds B -
hypokinesiai C - restorative period=
broken horizontal lines - confidence
interval of the control. Abscissa -
time of the investigation (weeks)t
ordinate - coefficient (units).
C
3 t`
	 l
Fig. 2. Alteration of the water
metabolism regulation coefficient in
hypokinesia in dogs.
1)II.IGI,NAL PAGE I,,^ 	 3)p Po ()R 01JA t.I7'N.
The regulation of water metabolism occurs as a result of the in-
teraction of two systems--ensuring water consumption and regulating its
retention in the organism. Usually an organism's consumption of water
is a preliminary act that is related to future requirements. A feel-
ing of thirst almost never arises with normal intake of food and water,
in stable climatic conditions # with uniform activity of the organism
[11]. The subcortical center that regulates the retention of water in
the organiam l as is known, is the supraoptic and paraventrieular nuclei
of the hypothalamus. In the organism's normal living conditions there
is a close functional dependence between the tissue structures of these
nerve centers. Most commonly they function as synergists--on dehydra-
tion of the organism a feeling of thirst arises and the secretion of
antidiuretic hormone increases.
In pathologic conditions disturbances of the functions of one or
simultaneously of both nerve centers are possible. In an experimento
for example, it was shown that with failure of the supraoptic and para-
ventricular nuclei, the effect of satiation with water disappears, and
the animal dies of hyperhydration. Ando conversely t in the case of
impairment of the lateral hypothalamus and the nuclei of the white
substance of the brain the nondition of thirst disappears even in
marked exeiccation [10].
In our investigations the water metabolism regulation was evalu-
ated with the help of the water metabolism regulation coefficientg
which was specially proposed by us for this purpose. The stay of
healthy persons on bedreet led to an increase in the value of this
coefficient by 2 times. On restoration of motor activity its value
differed from the background value to an even greater extent (2.5
times).
In the case in which in the process of hypokinesia constant water
consumption was eff ectedg thereby artificially disrupting the func-
tional interrelation between the centers of water metabolism regula-
tion (the drinking center already could not realize its usual effects
on the supraeptic and paraventrieular nuclei of the hypothalamus),
4
the coefficient of its regulation exceeded the background value by
3 . 5-5.5 times. Apparently this is related to the fact that increase
of the thresholds of neuron excitability of the anterior hypothalamus
during limited mobility [2] leads to the formation of a more narked 	 18
range between accumulation of water in the organism and its elimina-
tion.
Noted in hypokinesia are a deterioration of the functional con-
dition of the central nervous system and the formation of two syndromess
vegetovascular dysfunction and marked neuropsychic asthenization of
the organism [7]. These syndromes are the cause of the reduction of
the resources of adaptative mechanisms t_.at control the interaction of
the organism with the environment. Therefore it is completely natural
that the disturbance in the nature of the interaction of the systems
that regulate water metabolism was manifested particularly graphically
on the restoration of motor activity, when increased demands again
began to be made on all the to some extent weakened systems of the
organism.
Thus, with relatively rapid adjustment of a number of parameters
of water metabolism which are necessary for activity of the organism
in new conditions of its existence (normalization of the total fluid
content in the organism already during the lot week of restoration of
motor activity), its delicate regulation, which requires a certain
lability of intersystem interrelations (for which the considered
coefficient can serve as an index), remains disturbed longer and is
not normalized during the entire 3-week observation period. In our
opinion it is possible to obtain useful information on the peculiari-
ties of the alteration of water metabolism regulation in conditions of
sepcific effects with the help of the coefficient proposed by us.
5
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biol(ail i med t	 [ Pressing Questions of Spa" Biology aM
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6


Water metabolism regulating mechanisms in hypokinesia

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