Using special hypokinetic cages, the volume changes of circulating blood, its hematocrit and protein content, volume ratios between extra- and intracellular liquids in the body, as well as electrolyte content in the blood and myocardium during hypokinesia were investigated experimentally in rabbits

Fedorov, B. M.

Krotov, V. P.

Zhuravleva, Y. N.

English

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NASA TM-75954
CHANGES OF SOME BLOOD INDICES AND MYOCARDIAL ELE;CTROL-1-TE
CONTENT DURING HYPOKINESIA
B. M. Fedorov, V. P. Krotov, Ye. N. Zhuravleva
(NASA-TH-75954) CHANGES OP SOME BLOOD
	 NSO-15798
INDICES AND !MYOCARDIAL ELECTROLYTE CONTENT
D112ING HYPOKINESIA (National Aeronautics and
Space Administration) 12 p AC A02/e? 1101
	 Unclas
CSCL 06S G3/52 46906
Translation of: "Ob izmenenii nekotorykh pokazateley
krovi i soderzhaniya elektrolitov v miokards pri gipo-
kinezii," Patologicheskaya Fiziologiya i Eksperimental'-
naya Terapiya, No. 6, November-December 1973, pp. 27-31.
a o
C\j 	
J^O
NATIONAL AERONAUTICS AND SPACE PDMINISTRATION
WASHINGTON, D.C. 20546	 NOVEMBFR 1979
rc
UDC 612.766.2-08:[612.1+612.172.015.31
CHANGES IN SOME BLOOD INDICES AND MYOCARDIAL
ELECTROLYTE CONTENT DURING HYPOKINESIA
E by
B. M. Fedorov, V. P. Krotov and Ye. N. Zhuravleva
The authors investigated experimentally the volume
changes of circulating blood, its hematocrit and pro-
tein content, volume ratios between extra- and intra-
cellular liquids in the body, as well as electrolyte con-
tent in the blood and myocardium during hypokinesia. In-
vestigations were conducted on 112 rabbits (64 test and
48 control animals) placed as long as 62 days in special
hypokinetic cages. Electrolyte (K, Na, Ca and Mg) con-
centration and water content in the serum, hematocrit
index, and hemoglobin count were determined initially
and every 7 days; the other indices were measured after
the animals were killed. The measurement technique is
described. Results obtained are displayed in three
tables. Pronounced changes in the water-electrolyte
metabolism occurred in the test animals: the amount of
extracellular fluid was reduced, while the amount of
Intracellular fluid was increased; and sodium ion con-
centration decreased in the serum and increased in the
myocardial cells. Blood plasma volume and its albumin
content, which decreased duirng the first month of ex-
periments, were restored during the second month. How-
ever, the hematocrit index, which decreased by the end
of the first month, remained unchanged to the end of
the experiments.
At present hypokinesia is one of the basic problems of 	 /27 *
the pathological physiology of extreme states. Prolonged re-
duction in motor activity is noted in the most diverse situations--
Numbers in margin indicate pagination in original text.
1
fI
during a stay in small-sized pressurized chambers, under condi-
ions of a strict bed-confinement pattern in the clinic, etc.
'
	
	 It has been shown on healthy people that under the influence
of a lengthy reduction in motor activ.._: with strict immobiliza-
i	 tion in a plaster cast or in a strict tied-confinement pattern
a	
-
f
	a number of pronounced changes emerge on the part of the osteo-
muscular system (intensified breakdown of proteins in the muscles
and atrophic changes in them), cardiovascular system (detraining
of blood circulation system, reduction in orthostatic stability),
nervous system (dystonia of the autonomic nervous system and
asthenia of the central nervous system), and pronounced shifts
develop in the we-.ter-saline metabolism [1-6, 8 3 10, 14, 19J.
The question of changes in the volume of the circulating
blood and erythrocyte mass during hypodynamia has been amhigu-
ously covered in the literature, which is linked to a con-
siderable measure with the duration and conditions of experiments
[13, 22, 243. In.experiments on animals the effect of hypo-
kinesia is closely linked to the degree of immobilization and
species peculiarities of the organism. On rats it was established
-,hat under the influence of hypokinesia a stress reaction emerges,
protein breakdown increases [18], oxygen consumption by the tissues
rises [71, and a certain group of muscles atrophies [151. Strict
immobilization of rabbits produces serious damages to the cardio-
vascular system and death of the test animals in the space of
several weeks [16]. In the experiments with less strict fixing
of the rabbits in special hypokinetic cages a Pronounced stress
reaction does not develop in the animals, and under conditions
of thorough care they undergo 2-month hypokinesia without serious
damage of the internal organs. Here there is a clear change in
the functional state of the higher autonomic centers of the brain,
the hormonal and mediator metabolism of the organism is disrupted,
and the content of water and Na in the skeletal muscles rises
[9-12, 171.
2
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i
It is generally acknowledged that during hypokinesia the
blood circulation system is one of the most vulnerable. Here
in the mechanisms of circulatory disorders of primary importance
In addition to the changes in vascular tone.are the changes in
cardiac activity, volume of circulating blood and water-saline
balance of the organism.
We studied the changes in the volume of circulating blood,
its hematocrit and protein composition, correlation of volumes
of extracellular and intracellular fluid of the organism, as
well as the content of electrolytes in the blood and myocardium
during hypokinesia.
Technique
Experiments were conducted on 112 male chinchilla rabbits
(64 test and 48 control) weighing 3300-4000 g. All the animals
received the same food.
To limit the motor activity the rabbits were placed in
special hypokinesic cages whose walls were moved as the animals
lost weight.
In the initial state and further every 7 days the concen-
tration of electrolytes (K, Na, Ca and Mg) and water in the
serum, the hematocrit index and the hemoglobin quantity were
determined in the experimental and control rabbits.
Determination of the sizes of the fluid spaces in the
organism was based on the principle of dilution of the indi-
cator. Simultaneous intravenous administration of a certain
quantity of indicator mixture T-1824, sucrose and antipyrine,
made it possible to measure the volumes of plasma, extracellular
fluid and the total water in the body during the experiment
several times in the same animals.
/28
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The animals were killed with an electric current. In the
cardiac muscle the water, K, Na and Cl contents were analyzed.
The electrolyte concentration in the serum and tissues of the
myocardium was determined by the method of flame photometry (K
and Na--on a flame photometer of the Zeiss firm, Ca and Mg--on
an atomic-absorptian flame spectrophotometer). The Cl content
in the serum and tissues was determined by the method of mercuri-
metric and amperometric titration. The protein quantity in the
serum was determined by refractometric method, and its fraction--
by the method of electrophoresis on paper. The intracellular
concentration of electrolytes in the myocardium was analyzed
by the computation method according to tho Cl content [21].
Results
In the experiments with hypokinesia the weight of the rabbits
was reduced by the 15th day on the average by ?1X, by the 30th
day--by 211, and by the 60th --by 27% of the initial amount.
Reduction in the weight of the test rabbits could be linked
to dehydration of the organism or to changes in the plastic meta-
bolism towards dominance of the catabolic processes.
The total quantity of body water was reduced by the 30th
day of hypokinesia on the average by 545 ml, and by the 45th--by
495 ml. However, in conversion of the fluid quantity per unit
of weight the amounts did not significantly differ from that
established for the same animals before the start of the experi-
ment and in the control animals. Thus, before the experiment
the quantity of water was 677+21 ml/kg, after 30 days of hypo-
kinesia--669+10 mi/kg, after 45 days of hypokinesia--653+3 ml/kg.
(
	
	
In the same experiments with hypokinesia the quantity of
extracellular fluid was reliably reduced from 179.9+4.6 to 153.8
+8.1 ml/kg during 30-day hypokinesia, and from 177.3+1.9 to
4
i
-mss.
166.3+1.9 ml/kg in 45-day hypokinesia. The quantity of intra-
Cellular fluid in the organism determined by computation in these
`	 periods was increased.
The total volume of plasma after 30 days of hypokinesia was
reduced by 23%. in computation per unit of weight--by 156. In
45-day hypokinesia the total volume of plasma was reduced by 20 %2
but its volume per unit of weight did not differ from the initial
value. After two months of hypokinesia the total volume of
plasma remained reduced, but in conversion per unit of body weight
was not reduced, and even was increased as compared with the
initial amount (table 1).
Hypokinesia produced changes in the content of total protein
and the correlation of its fractions in the serum. The protein
concentration in serum was reduced f nom 7.01+0.14 to 6.34+0.17g%
(D 60.01) after three-week hypokinesia, and even more (to 6.08
+0.Ag%) (D G 0.001)--by the end of the first month; by the seventh
week of the experiment it approached the initial level (6.84+0.13
g%), and by the 62nd day corresponded to it (7.08+0.17 g%).
The concentration of albumins in the serum by the end of the
first week of hypokinesia was reduced from 3.65+0.18 to 2.93+
0.19 g% (D 60.005), staying on this level to the end of the third
week; by the end of the first month it was reduced even more (to
2.41+0.06 g%; D/-0.001), however during the second month of the
experiment it was restored, reaching by the 45th day 3.51+0.28 g%
and by the 62nd day-- 3.96+0.25 g%. The globulin concentration
in the serum, on the contrary, increased during the first 30
days of hypokinesia and was reduced during the second month. Here
the albumin-globulin coeffficient from 1.08 in the initial state 	 /29
was reduced to 0.66 by the end of the first month of the experi-
ment and increased to 1.26 by the end of the second month.
ii
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1 '4
5
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TABLE 1
^
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r
CHANGE IN VOLUME OF CIRCULATING BLOOD AND PLASMA IN DIFFERENT
PERIODS OF HYPOKINESIA (M+m)
Duration of	 olume of plasma
	 Volume of circulating
experiment ( in day s	 blood
(30)
30(8)
45(8)
62(14)
*D /-0.05
**D L0.01
***D L 0.001
64.6+6.5 43.1+1.0 266+14.1 70.9+3. 6
10.1+3.7*** 36.7+1.3** 177:x+5.8*** 59.3+2.1*
32.4+x.1*** 41.5R .26 201.0+1.6*** 63.0+1.4
41. 4+1.4** 50.571.7**	 1 201.3+M.5*** 	1 71.9±3.1
Note: Here and in the remaining tables D i3 computed as compared
to the initial data. In parentheses--number of animals.
TABLE 2
CHANGE IN HFMATOCRIT AND HEMOGLOBIN CONTENT OF BLOOD
PERIONi OF HYPOKINESIA (M+m)
IN DIFFERENT
Duration of Hemat ocritOn % a	 Hem ELlohlijO r, x)
exper , een tLin days- _con trol experiment cont rol
	_ experiment-^
Initial data 42+0.8 42+0.4 13.9+0.15 13.7+0.09
1 43+1.5 41+`1.2 14.0+0.21 14.0+0.18
7-8 43+'E.7 43+1.3 13.8+0.26 14.2+0.29
14-15 43+1.3 44+1.2 13.9+`0.18 14.3+0.17*
21-22 41+1.5 41+0.9 14.1+0.36 14.1-+0.27
28-29 41+1.4 38+'1.2* 14.2+0.23 13.3 +0.21
35-36 41+1.'7 34+1.i** 13.9+0.20 12.6 +0.24*
42-43 42+1.5 35+1.3* 13.8'+0.28 11.4 +0.30**
47-48 42+2.0 33+1.5** 13.8+0.30 10.9 +0.27***
60-62 42+1.8 30+1.1*** 13.9+_0.25 9.7 +0.33***
*D /_0.05
**D L 0.01
***D/.0.001
Under the influence of hypokinesia the hematocrit number was
gradually reduced--by the end of the second month of the experi-
ment by 29% (table 2). Similar changes were observed also'in the
ratic of hemoglobin, whose content on the 62nd day of hypokinesia
was reduced by 30: (see table 2).
The volume of circulating blood relative to a unit of
weight was reduced on the 30th and 4 5th day of hypokinesia, but
L
6
f9 a
fJ	 _
within 2 months was normalIzed. This normalization was linked
to the increase in the volume of plasma while the erythrocytic
mass remained reduced by 20% as compared to thr initial amount.
With 2 month hypokinesia no reliable changes in the X and Mg
concentration in the serum were noted as compared to the initial
amounts and control data. The Ca concentration was reduced.for
a short time in the fourth week of hypokinesia from 6.5 +0.18 to
5.6+0.17 mequiv/1 (D/-0.05).
The Na concentration in the serum was reduced by the end of
the first month of the experiment from 147+1.6 to 141+1.8 mequiv/1
(D 40-05). This reduction was maintained until the end of the
experiment (by the 62nd day of the experiment it wao equal to 138+
1.9 mequiv/1; D 40.01).
TABLE 3	 /30
INTRACELLULAR CONCENTRATION OF Na AND K IONS IN DIFFERENT SECTIONS
OF THE MYOCARDIUM DURING 2 MONTH HYPOKINESIA (M+m)
ElectrolytelGroup of animals Right	 Left	 Interventricular
 septum
Sodium
	
Control
	 39.9+2.3 21.7+3.4 23.9+2.8
Experimental	 47.5+2.1* 33.5+2.7* 32.2+3.3*
Potassium
	
Control	 126+I1 	 128.5+9 	130.5+12
Experimental	 134..-8+8	 133.9+10 128.8+6
A D Z-0.05
 -	 -- 
The intracellular concentration of Na and K ions was deter-
mined in different sections of the ventricular muscle of the heart
in experiments with 2-month hypokinesia. By this period the intra-
cellular concentration of K ions was practically unchanged, while
that of the Na ions was increased in all sections of the cardiac
ventricles, especially in the tissues of the left ventricle (table 3).
Discussion	 1
In discussing the mechanisms of the changes occurring under
the influence of hypokinesia in the water-electrolyte metabolism
7
it is possible to explain the redistribution of fluid in the
aorganism by intensification in the catabolic processes that govern
an increase in the content in the cell of the quantity of endogenous
water and that	 retain the water of osmotically active molecules.
An increase in the later stages of hypokinesia in the intra-
cellular concentration of Na ions can have several causes, among
which serious attention should be given to the reduction in the
I	 energy supply to the work of the sodium-potassium pump of the
cellular membrane. This is indicated by a number of indirect
s
data, in particular the sharp reduction in hypokinesia in the con-
tent in the myocardial tissues of the mediators that stimulate
the cardiac muscle [11, 12], decrease in the quantity ofcristae
in the mitochondria [10], and disruption in the processes of
oxidizing phosphorylation [7]. It should be noted that an increase
in the intracellular concentration of Na ions has significance for
G	 the change in excitability of the cardiac muscles, and affects
7
the amount of transmembrane potential and heterochronicity in the
myocardial fibers.
The cited data make it possible to propose the presence of
a causal link between the increase in the quantity of albumins and
the increase in the volume of plasma at the later stages of hypo-
kinesia. This agrees with the known assumptions on the important
role of plasma proteins, especially albumins, in the regulation
of water metabolism.
A clear reduction in the hematocrit in the dynamics of
hypokinesia we explain first of all by the changes in the apparatus
of regulation for the autonomic functions of the organism [11, 12,
17]. This assumption agrees with the data on the stimulating effect
of the sympathetic sections of the nervous system on the erythro-
poiesis [20,23] and sharp reduction in the function of these sec-
t	 tions of the nervous system during hypokinesia [11, 12, 171.
i
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10
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Changes of some blood indices and myocardial electrolyte content during hypokinesia

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