Glycolysis and the intensity of protein synthesis were studied in 140 white male rats in subcellular fractions of the myocardium during 45 day hypodynamia and hyperbaric oxygenation. Hypodynamia increased: (1) the amount of lactic acids; (2) the amount of pyruvic acid; (3) the lactate/pyruvate coefficient; and (4) the activities of aldolase and lactate dehydrogenase. Hyperbaric oxygenation was found to have a favorable metabolic effect on the animals with hypodynamia

Makarov, G. A.

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	 (NASA-TK-76012) EFFECT OF HYPERBARIC
	 N80-21974
OXYGENATION ON CARBOHYDRATE NTABOLISM
PROTEIN SYNTHESIS IN THE NYOCARDIUN DURING
SUSTAINED HYPODYNAMIA (National Aeronautics
	 Unclas
and Space Administration) 9 p HC A02/9F 101 G3/52 46857
NASA TEC11NICAL MEMORANDUM	 NASA TM-76012
EFFECT OF HYPERBI.RIC OXYGENATION ON CARBOHYDRATE
METABOLISM AND PROTEIN SYNTHESIS IN THE MYOCARDIUM
DURING SUSTAINED HYPODYNAMIA
G.A. Makarov
Translation of"Vliyaniye giperbaricheskoy oksigenatsii
na uglevodnyy obmen i sintez belka v miokarde
pri dlitel'noy gipodinamii".
Kardiologiya, Vol. 14, No. 2, 1974, pp 73--77
e
	
NATIONAL AERONAUTICS AND SPACE ADMINISTRATION 	 A
	
JANUARY 1980	 U?`WASHINGTON D.C. 20546	 /G ^L
k	 f^ RECE
IVED1	 ^A 511 
t< ACCESS p
	
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UDC 612.766.2-08:612.173.1.015.348.014.464:612.274
EFFECT OF HYPERBA RIC OXYGENATION IN CARBOHYDRATE
METABOLISM AND PROTEIN SYNTHESIS IN THE IdYOCARDIUM
DURING SUSTAINED HYPODYNAMIA
By
G. A. Makarov*
	
Prolonged restricted motor activity (hypodynamia) is one of the factors
	 X73**
that detrains the cardiovascular system and the apparatus of its regulation, and
promotes the appearance of atherosclerosis, coronary insufficiency, disorders in
the contractile capacity of the myocardium, and orthostatic instability all the
way to collapse L2, 43. The most significant changes during hypodynamia are
characterized by a disorder in the water-salt exchange [9], weakening of hormonal
activity and exhaustion of the supplies of catecholamines in the tissues [10],
decrease in the synthesis of tissue proteins and increase in the breakdown L163,
and change in the processes of energy formation in the myocardium [6, 1 33. The
severe conditions of prolonged hypodynamia are characteristic for the clinical
	
treatment of cardiovascular diseases,in particular, myocardial infarct. Here
	 /74
often unfavorable changes are observed in the metabolic processes aggravating the
course of the main disease, and rehabilitation of such patients to a considerable
measure depends on the elimination of the consequences of the forced hypodynamia.
Recently in the treatment of many cardiovascular diseases occurring with
distortion of myocardial metabolism, hyperbaric oxygen treatment has been success-
fully used [14, 203. Taking into consideration the increase in the energy poten-
tial of the tissues and the favorable reconstruction of different metabolic links
*
Department of Pathological Physiology of I. P. Pavlov Ryazan' Medical In-
stitute.
**Numbers in margin indicate pagination in original foreign text.
1
during the effect on the organism of slight pressure of pure oxygen [5,7] it
seemed oxpedient to us to study the effect of hyperbaric oxygenation on the
main processes of vital activity of the myocardium--bioenergetics and plastic
supply of the functions, effectiveness and lability of which determine as a
result the adaptation of 7.-.e organism to the various extreme situations [8],
including prolonged hyp,-',,-namia.
r'aterial and Methods
Experiments were conducted on 140 albino male rats weighing 170-240 g.
Hypodynamia was created by keeping the animals for 45 days in close individual
cages that restrict the mobility of the animals in all directions. In the last
2 days the animals were placed for 3 h in a decompression chamber with pure
oxygen under pressure of 1.5 ata, i.e. ,under conditions of hypoxia that did not
have a toxic effect on the organism L1, 73. The oxygen was periodically exchanged=
carbon dioxide and water vapors in the chamber (volume 15 1) were absorbed by
soda lime and silica gel. After exposure in the decompression chamber the rats
were kept for 3 h under normal conditions, then they were killed; the effect of
oxygen on the metabolic processes even after a single session for 1 h was
preserved for over 24 h [5]. Analogously hyperbaric oxygenation was conducted
on intact animals. Tha intensity of glycolysis in the system of energy production
of the myocardium, was judgod from the change in the content of substrates:
glycogen [12], pyruvate [18], lactate [171, lactate/pyruvate coefficient and
activity of enzymes of glycolysis: aldolase [15] and lactate dehydrogenase--
LDH [21]. The activity of aldolase was expressed in conventional units of LDH--
in the blood in Vroblevskiy units, in the myocardium--in micromoles per minute
for 1 g. The intensity of protein synthesis in the mitochondria and post-
mitochondrial supernatant was judged according to the rate o f inclusion of
glycene-C 14
 introduced intraperitoneally in a dose of 25 µCu per 3.00 g of weight
6 h before death. The mitochondria were isolated by the method of differential
centrifuging [11] in 0.25 M solution of sucrose (pH 7.4) with 0.001 M of EDTA.
The protein of the mitochondria and supernatant was precipitated by a 10%
solution of tricholoracetic acid, reprecipitated by a 5% solution of it, then
successively washed with alcohol, mixture of alcohol and ether (1:1), ether and
dried for 12 h at 60 0. The radioactivity of the preparations was measured on
an end-type counter BFL-T-25 with conversion unit ? gyp-16. The specific activity
was expressed in impulsos por minute for 10 mg of protein.
2
Y
•	 d
T
Results and Their Discussion
Prolonged hypodynamia induced in the animals serious changes in the meta-
bolism of the myocardium resulting in reconstruction of the processes of energy 	.
formation and decrease in the plastic supply of the functions. Thus, in the myo-
cardium the amount of pyruvic (by 17.6%) and lactic acids (by 53.6%) increased,
the lactate/pyruvate coefficient increased= its rise reflects the hypoxic nature
of metabolism in the tissues X19]. A considerable exhaustion of the supplies of
glycogen was also noted (by 56.76). The increase in the lactate/pyruvate coeffi-
cient observed during hypodynamia, as well as a significant increase in the
activity of the enzymes of glycolysis (see figure)--aldolase (by 56%), and LDH
(by 25.596)-- indicate the significant intensification of the processes of glyco-
lysis and glycogenolysis, inhibition of pyruvate inclusion in the Krebs cycle and
shift in the lactate dehydrogenase reaction towards the accumulation of lactic
acid.
Analogous changes in the content of substrates and activity of the enzymes of
glycolysis were also observed in the blood of animals with hypodynamia (see table
and figure).
Change n Activity of A ldolase and Lactate Dehydro-
genase in % of changes of control) during Hypo-
dynamia and Effect of Hyperbaric Oxygenation
A --aldolase; B--lactate dehydrogenase= I--blood=
II--heart. Light columns--hypodynamia, dark--
hyperbaric oxygenation, hatched--hypodynamia and
hyperbaric oxygenation. Arrows indicate statis-
tically reliable differences with the control. (p c9.5)
Intensification in the power of glycolysis in the myocardium of the experi-
mental animals, apparently, is a compensatory factor in ,maintaining the energy
potential, for during hypodynamia there is a considerable reduction in oxygen
consumption by the homogenates of the heart with the use of various substrates
[3], as well as a drastic inhibition of the processes of oxidative phbsphorylation
[13] i.e., the effective functioning of the mitochodria, the main power generators
of the cell, is blocked. In an electron microscopic study in these same periods
of hypodynamia swelling of the mitochondria, reduction in them of the quantity
3
cristae, disorder in the structure of the cellular membranes were revealed [3,4],
i.e., changes that indicate a deficit of oxygen.
CHANGE IN MMICES OF CARBOMPATE METABOLISM AND PROTEIN SYNTHESIS IN RAT MYO -
CARDIUM DURING PROLONGED HYPODYNAMIA AND EFFECT OF HYPERBA RIC OXYGENATION
Series of	 Statistics ly- I Pyruvate 	 ctate	 ctate/pyruvate Inclusionl4f
experiment	 indicator oge m	 coefficient	 glycene-C in
lood myo- lood myo lood yocar-	 protein(in imp
1
car_
	
	
car	 dium
	 min per 10 mg
di	 di	 of nrotein
ito-	 Isuper-
13.8I 8.1 We 308M
= n^
430
20.0
2,0
0.12
1.7
0.09
15.8
1.2 0.9
7.9
'21.G 25.
I.4f 18G- 19 2.0- 20,90 21.2* 116.0 10.6 188- 164-
-w 8.5 0,07 0.1 1,3 1.4 16.4 11.6
n 10 8 8 8 8 8 8 6 6
M MO2 2.96- 2.14- 13,6 12.3 4.6 5.7 498* 390'
= ni 19.2 0,13 0,16 1,12 1.1 26.6 19.9
n
M
8 6 6 6 6
i 1 0
6 6 6 6.
0..519 062 086 160 d0 t9
t	 1 3IE
*--differences with control are statistically reliablsfp *.05) 1 n--
number of experiments.
Control(Intact
animals)
Hypodynamia
Hyperbaric
oxygenation
Hypodynamia and
hypercaric
oxygenation
Designations:
Naturally, under these conditions the plastic supply of the. myocardial functions
is also reduced. In th:1
 experimental animals a sharp inhibition was noted of the
incorporation of glycene-C14
 (see table) in the total protein of the mitochondria
(by 53.3%) and supernatant (by 56.9%). Apparently, the reduction in the level of
phosphoryla.tion in the myocardium leading to a delay in the process of formation
of macro-ergic phosphorous compounds, and depression of the reparative processes
are the basis for the observed detraining of the heart during hypodynamia and
drop in its weight L2].
Taking into consideration the favorable changes in me tabolism and intensifi-
cation in the energy potential of the tissues in hyperbaric oxygenation E1 , 73
we considered it expedient to use this biological method of intensifying the
adaptation reserves of the organism during hypodynamia.
Exposure of intact animals in a medium of pure oxygen induced in the blood
and tissues of the heart a considerable reduction in the lactate/pyruvate ratio
and decrease in the activity of LDH (see figure), which indicates the dominance
of the oxidative transformations of the substrates in the Krebs cycle [19]. The
observed increase in activity of aldolase and concentration of pyruvate on the
background of a reduction in the content of lactate indicates the intensification
	 /76
4
iof the functioning of the Embden Meyerhof cycle, here the resynthesis of glyco-
gen remains on the optimal level. In a study of synthetic processes in the sub-
cellular factions of the myocardium an increase was revealed in the intensity
of protein synthesis in the mitochondria by ?8.36, in the supernatant by 27.4%
(see table).
Hyperbaric oxygenation had a favorable metabolic effect on the animals with
hypodynamia. In the blood and myocardium a reduction was noted in the quantity
of lactic and pyruvic acids, the lactate/pyruvate ratio, and glycogen synthesis
increased.in
 the myocardium. The activity of aldolase and LDH was almost
normalized (see figure). Light hyperbaric oxygenation, increasing the consumption
of oxyger by the homogenates of the heart and the ei-'_ctiveness of oxidative
phosphorylation in the intact animals L1 ,53 probably governs, judging from our
data, the similar changes in the myocardium of rats during hypodynamia, which
creat3s the necessary energy base for intensification of the reparative processes.
In fact, the intensity of protein synthesis in the cytostructures of the myo-
cardium, especially in the mitochondria, in rats of this series was considerably
more pronounced than in animals with hypodynamia, and approached the normal.
Thus, taking into consideration the favorable effect of light hyperbaric
oxygenation on the metabolic processes in the myocardium, it is expedient to in-
clude hyperbaric oxygen therapy in the arsenal of resources for directed effect on
the myocardial metabolism in the case of forced prolonged hypodynamia. The
unidirectional nature of changes in the activity of glycolytic enzymes, concen-
tration of substrates and lactate/pyruvate ratio in the blood and myocardium in
experimental animals and in the period of hyperbaric oxygenation makes it possible
to use these hematological indices as criteria for evaluating metabolic shifts
in the myocardium.
Conclusions
1. Prolonged restricted motor activity in animals induces in the blood and
myocardium an increase in the concentration of lactic and pyruvic acids, lactate
Fyruvate coefficient, activity of glycolytic enzymes--aldolase and lactate dehydro-
genase, exhaustion of supplies of glycogen and reduction in intensity of protein
synthesis in subcellular fractions of the myocardium.
2. Hyperbaric oxygenation, increasing the oxidation of pyru+ate
I
5
and intensity of synthetic processes in the myocardium, leads to a reduction in
the concentration-of pyruvate and lactate in the' blood and myocardium of animals
with hypodynamia; here the activity of the enzymes of glycolysis is normalized and
the intensity of the reparative processes in the myocardium is considerably increased.
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7


Effect of hyperbaric oxygenation on carbohydrate metabolism protein synthesis in the myocardium during sustained hypodynamia

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