The features of cholinergic processes in the heart on the 4th, 8th, 16th and 30th days of hypokinesia were studied in experiments on 382 albino rats. It was shown that hypokinesia is attended by increased acetylcholine content in the atria, reduced choline acetyltransferase activity in the atria and ventricles and by increased activity of acetylcholinesterase in the ventricles and of pseudocholinesterase in both parts of the heart. The sensitivity of the heart to exogenic acetylcholine and to stimulation of the vagus nerve increases

Babinskaya, L. N.

Bolyarskaya, V. A.

Bondarenko, Y. I.

Fayfura, V. V.

Markova, Y. A.

Rosolovskiy, A. P.

English

NASA Technical Reports Server

0
 
NASA TECHNICAL MEMORANDUM NASA TM-76O44
 
FEATURES OF CEOLINERGIC CARDIA REGULATION 
UNDER CONDITIONS OF HYPOKINESIA 
Ye. A. Markova, Yuf. I. Bdndarenko, V. A. Bolyarskaya, V. V.
 
Fayfura, A. P. Rosolovskiy, and L. N. 3abinkr .......
 
N80-18687 I
 
- NASA-TM-7604 4 ) FEATURES OF'CHOLINERGIC 
CARDIA REGULATION UNDER CONDITIONS OF 
HYPOKINESIA (National Aeronautics and Space
 
Unclas
dministration) 10 p HC A02/F AOl CSCi 06C 

-------5------! 7225 91 ! 
Translation of "Osobennosti kholinergicheskoy regulyatsii serdtsa v
 
usloviyakh gipokinezii", Patologieheskaya fiziologiya i eksperimentalt naya
 
terapiya, No. 3 (May-June), 1979, pp 13-16
 
.r) 
~-j 2ixti0 g Bh1- ~ LC 
NATIONAL AERONAUTICS AND SPACE ADMINISTRATION
 
WASHINGTON, D. C. 20546 FEBRUARY 1980
 
https://ntrs.nasa.gov/search.jsp?R=19800010411 2020-03-21T20:05:50+00:00Z

STANOARO TITLE PAGE 
R2, G., t.on, Accosson No. 3. R.cip.o,, Cotoog No. 
4. Til. cod Sutitio 5, Rp.et Da19 
February 1980
 
Features of Cholinergic Cardiac Regulation 6. Por.rmlM Orgonl=aon Cod.
 
Under Conditions of Hypokinesia
 
7. Autho'(s) 8. P.rfo,ming Orgocnixotion R~pont No. 
ye. A. Marko~a;-Yv. 
-. ' 'Bpndareinko, V. A., W-).Work Unai No,
-Bolyarskaya,-V-; V.-TFyfura, A. T- Rosolovskiy
 
and L. N. Babinskava 11. Contract or G,.t No.
 
9. Ps0or,n~~ooion Noa o od Add,... NASH- 31 2 
SC IT N 13. Typo of Roport and Period Covered 
Box 5456
 
Translation
 
_ an-a Barhra rA 911n0 

aiona eronautics and Space Administration
 
Wasnington, D.C. 20546 14. Sp.noring Agen.y Cod*
 
5pplemenoorSo Notes 
Translation'of iDsoennosti,khotinergichekoy.regulyatsii serdtea v 
usloviyakl gipokinezii", patologicheskaya fiziblogiya i eksp~rimental'naya 
terapiya, No.'3 (May-June), 1979, pp 13-16 
16, Absttrto 
The features of cholinergic processes in the heart on the 4th, 8th, 16th­
and 30th days of hypQkinesia were studied in experiments on 382 albino 
rats. It was showi that hypokinesia is attended br increased acetyl­
chline content in,the atria, reduced choline.acetyltransferase activity 
in the atria and ventricles and by increaseddctivity of acetylcholine­
sterase in the ventricles and of Iseudocholinesterase in both parts of
 
the heart. The' sensitivity of the heart to exbg&nic acetylcholine and
 
to stimulation'of the vagus nerve increases.
 
17. Kay Words (Selcted by Author()) J8. O hfwt; on srot en This copytig--
Soviet vork is reproduced aed soldi
 
by -NgTS under license from VAAP, ihe 
Soviet copyright agency. N- -furtber­
-
copying is permitted without per

mission from VAAP. 
} 19. SecuIty Clossif. (.of t npofl) 20. Socuvty Cles (of ,f.this 1 .0o)o 
Unlassified:- Unclassified 
UDC 612.178.1-06:612.766.2
 
FEATURES OF CHOLINERGIC CABDIAC RDSUIA2ION UNDER CONDITIONS OF HYPOKINESIA 
By Ye. A. Markova, YU. I. Bondarenko, V. A. Bolyarskaya, V. V. Fayfura, A. P. 
Rosolovskiy, and L. N. Babinskaya, Department of Pathological Physiology of 
the Ternopol' Medical Institute 
The features of cholinergic processes in the heart on 
the 4th, 8th, 16th and 30ieth days of hypokinesia were 
studied in experiments on 382 albino rats. It was shown 
that hypokinesia is attended by increased acetylcholine 
content in the atria, reduced choline acetyltransferase 
activity in the atria and ventricles and by increased 
activity of acetylcholinesterase in the ventricles and of 
pseudocholinesterase in both parts of the heart. The 
sensitivity of the heart to exogenic acetylcholine and 
to stimulation of the vagus nerve increases. 
Clinical-physiological and experimental studies have demonstrated that /13* 
in the state of hypokinesia there is a lack of coordination in the coordinated 
activity of the regul&tory systems in the organism. The functional state of 
the higher autonomous centers of the brain is sharply disrupted [9], the 
equilibrium between the parasympathetic and sympathetic sections of the auto­
nomous nervous system is shifted [7], the activity of a number of organism 
*Nuxtrers in margin indicate pagination in original foreign text 
1 
including the heart [6]... The impoxtanceof considering the cholinerTic­
adrenergic correlations. in Itypokinesia-has _1 htnd -practical .reflection in 
the recanrendation- to .detanine the bi6lobicall acttev substances under 
conditions of the effect of -space flight factors 13] and the Kerde vegetative 
index to evaluate the state-of the operators [4]. 
rThis work presents data on the features of cholinergic processes in 
the heart of rats during 30-day hypokinesaa. There are very few articles 
on this question [1, 2, 5, 8]. 
Technique 
Experiments were set up on 382 albino rats of both sexes weighing 120­
200 g. The hypokinesia nodel was created by placing the animals in special 
chanbers that restrict motor activity. The control animals had free notion. 
The content of acetylcholine was detennined in the musculus rectus 
abdominis of the frog [12] and was expressed in micrograms per 1 g of moist 
tissue. In order to increase the sensitivity of the preparation acetone 
was used [13]. The activity of choline acetyltransferase was detemined [il] 
and expressed in micrograms of acetyIcholine synthesized by #he atria or 
ventricles in the space of one hour at 37 0C in conversion for 1 g of tissue 
dried with acetone. The Yaplan-Limann enzxe ,og acetylation was extracted 
from the liver of pigeons- [10]. The activity of cholinesterase was analyzed 
mancmetrically on the Varburg apparatus. The heart was washed in a 0.9% 
solution of NaCI, the ventricles were separated from the atria, dried with 
filter paper and pulverized in a mortar with the addition of 25 uM of NaHCO 3 
2 
solution C6 ml for the.atria, 10 xll for the'ventriclesl. They -were extracted 
for one hour.. The reaction mixtura consisted of 1.5 3a1 of extract and 0.5 
ml of substrate dissolved' in 25 iM of NaRf0 3 solution. Acetyl-$methylcholine /14 
NeC) was used' as-the substrate for acet icholinesterase, and butyrylcholine 
CBuC) tor pseudocholinesterase (final concentrations 2.2 m). The activity 
of the enzymes was expressed in milligrams of substrate split by the extract 
in the space of one hour at 380C in conversion for one gran of moist tissue. 
The sensitivity of the heart to exogenous acetylcholine was studied by 
introducing the substance into the femoral -vein in a dose of 10 pg per 100 g 
of body weight. The degree of bradycardia was taken into consideration, as 
well as the duration of the negative-chronotropic effect. The EKG was 
recorded on an ink-writing oscillograph. The right -vagus nerve was stimulated 
by the ESL-2 electrical stinulator (frequency 50 Hz, duration of inpulse 
5 ms), at first for 5 s, and then, after restoration of the initial rhyth-, 
repeatedly for one minute. The degree of slowing down of the cardiac contrac­
tion was computed. 
Results and Discussion
 
The generalized data on the content of acetylcholine, activity of choline­
acetyltransferase and cholinesterase in the heart in the space of 30-day 
hypokinesia are presented in table 1. 
The content of .acetylcholine in the heart of control animals fluctuated 
in fairly broad lUnits, wtereupon the atria was six .times richer in this 
mediator than the ventricles. In lypokinesia the content of acetylcholine
 
3 
in the atria was gradually increased, starting frcm the 8th day, and by the 
30th day- was 1.5 times greater than the control amounts. The level of acetyl­
choline in the ventricles displayed a relativa stability .and for 30 days
 
practically was not changed. At 	the end of the observation the correlation
 
between the concentrations of acetyIcholine in the atria and the ventricles
 
shifted in favor of the atria.
 
TABLE 1. 	 CONTENT OF AET OLNE, ACTIVIT? OF CHOLINACETYLTRANSPEPASE AND 
CHOLINESTEPS IN HEAT NORMALLY AND DURING HYPOKINESIA (M+t) 
Index Control 	 Day of. Hypokinesia 
Content of acetyl-	 I 4.ft 8-f 16-A - S0­
choline: 	 I';( ~ ( -15,40.-+0,39*(l0)-4"" 

Atria 3,72±0,27 (40) -3Z04±0,25(10):-t4,71±0,1 (10) 4,51-0,75 (10) 
Ventricles 0,63-0,04 (40) 0,52-0,08 (10) 0,78±0,10 (10) 0,62±0,07 (10) - O'67± (-0) 
Activity of cholin- ­
acetyltransferase: 
Atria 794-±60,8 (12)--,-- 726.L35,2-(10) 688-!79,8 (9) -63±-43,5*(I) 473--±-4,2(10)Ventricles 647--63,0 () [ 	 69±52(2) 58360,9 ()194±45,5(3) 
Activity of acetyl- " -­
cholinesterase: 
Atria 8,64±0,83"(t1V" 	7,84±0'60 (10) I 12,15±0'62'(10) I 10,53-0,69 (10) 8,51=0,30 (11)
 
3,25±04 ) 5,27 77(10) 4,53-O,49'(10) 4,27-0,50*(l1)
Ventricles 3,070,21 (2. 
Actvity of pseudo­
cholinesterase:
 
Atria 44,75t 1,55 (11) 51l44±I,92(0 0) 45;56±2-8-(10)-_ 51,60±2.25(ll) 
Ventricles 15,61±L1,66(12) 18,41-±-0,76 (11) 24,57±1,81*(I0) 26,94-±E74*(12) 33,68± 2 ,06*(ll) 
iUnits of measurement given in section "technigque."
 
Note. The asterisk designates amounts that reliably differ from the controls.
 
In the parentheses number of experients. 
The activit of cholinacetyltransferase was- also higher in the atria, 
but the difference were less pronounced than in the distribution of acetyl­
choline. 	During the period of hypokihesia the activity of the enzyme was
 
4 
gradually reduced .inboth-sections of the. heart r whitdbecame especially 
notqeblebfr the 16tlhtday. In the atria this decrease was. less significant 
than in the ventricles. 
The activity of acetyl-and pseudocholinesterase of the atria in the 
control rats was roughly 2.5 times greater than that in the'ventricles. The 
breakdown ability of one gram of the atria in relation to MeC was 5.01-14.45 
ng of substrate, and in-relation to BuC--36.66-52.16 rg in 30 minutes. One 
gram of tissue of the ventricles in the same time broke down respectively 
1.99-4.10 mg of MeC and 6.46-27.71 DuC. The activity of acetylcholinesterase 
was reliably increased in both sections of the heart by the 8th day of hypo­
kinesia, then a decrease started that ended in the atria with caplete normal­
ization by the end of the observation. In the ventricles the activity of 
.this enzyme was also reduced after the 8th day, but by the 30th day had not 
reached the control amounts. The activity of pseudocholinesterase in the 
atria was increased already on the 4th day of hypokinesia, i.e., at an earlier 
stage than acetylcholinesterase. By the 16th day the activity of the enzyme 
had been normalized, but by the 30th a repeated increase was noted. In the 
ventricles the activity of pseudocholinesterase reliably rose only on the 8th 
day, i.e., later than in the atria. Then its activity continued to steadily
 
increase and hy the 30t day was doubled as caoared to the control.
 
The findings indicate that for hyjokinesia an imbalance is characteristic 
in physiological correlations betweeh individual links in the system cholin­
acetyltransferase-acetylcholinesterase. M4aintenance of the concentration of 
acetylcholine on a normal level in the cardiac ventricle and even an increase 
5 
0' 
TABLE 2. 	 SENSITIVITY OF THE IEART TO EXOGENOUS ACETYICHOLINE AMD TO STMUIATION OF THE VAGUS NERVE 
IN DIFFERENT PERIODS OF 1YPOKINESIA (Mi) 
Introduction of 
Acetylcholine Stimulation of" Vacus Nerve 
For 1 Minute (Degree of 
For 5 Minutes Delay in Rhvthm, %of Oriqinal 
Degree of Duration of Degree of Duration of Imnediately In 5 1n 30 In 
Conditions of Elperi- Delay in - radydara Delay in Bradycardia After Stimu- s s 1 mnn 
ments tin parentheses 1ythmr-% " s ltytmr s lation . . 
number of animals) of Original of Original . 
161-,7,±5 7,0-,0,24Control (121 	 2,77 13,7±L2,39 11,1±1,89 23,5±L3,03 39,2±-4,27 
t
Hy2o2inesia: 29,7±4,47--0,2 7,7 2,09 	 2:0,0--I,7951 ,51±.630,48 	 :
days I 	 25,0±2,77C12) 	 :-3,572418,6-- 1,84
20,9±-2,30 4,1=L-0,37 8,0-2,0-9- '2,07115,7 	 2,00 21,2--:1,5850±,7t i8,3 ±0 24- - . ,7=It ._055,8i,48 ,14A ,82 -± 8 days (12] '18,8=2,05 5,3=0,48 410, ,95 
16 days (121 19,0--4,19 4,7±-0,52 9,4-2,07 6,3±0,17 12,3±1,30 6,9±1,45 19,1!1,1430 days (l21 	
-. 
in it in the atria on the-30th-da, of 14pokinesia indicates considerable 
adaptation potentialities.-of the cholinergic -.xelation of tha.cardiovascular 
system. On the bther hand it is necessary%to assume that guarantee of' fairly 
high concentrations. of acetylcholine in the-hert ia linked not only to the 
activity of the synthesizing and splitting enzymes, but also to other factors-­
energy supply, level of initial products, and electrolyte caitosition of the 
medium. 
Data on the reactions of the heart to exogenous acetylcholine and to /16 
stimulation of the vagus nerve are presented in table 2. They indicate the 
increase in the sensitivity of the heart to exogenous acetylcholine which 
is manifest in an increase in the degree and duration of bradycardia. Experi­
ments with stimulation of the vagus nerve also indicate the increase in 
sensitivity of the heart to the cholinergic effects on the 4th-16th day. 
However by the 30th day a complete restoration of reactions to stimulation 
of the vagus nerve is noted whic was not observed with the introduction of 
acetylcholine from the outside. 
RFERCES
 
1. 	 Boyer, V. A. in Meditsinskive pobl fizichesko- ku'tury [Medical 
Problems of Physical Culture"], Kiev, No 1, 1971, p 10-14. 
2. 	 Boyer, V. A. V l gipokinez na funktsii i kholinergicheskur 
r. iyu serdts zhivotnvkk i xazlicbnvve vozrastnyva periody ["Effect 
of Hypokinesia on 'unction and Cholinergic Regulation of Heart of Animals 
in Different Age Periods"], author's abstract of candidate dissertation, 
Cherhovtsy, 1972. 
3. 	 Kratkiv spravochnik 2kosmicheko l i meditsine ["Concise Refer­
ence on Space Biology, and Medicine"], edited by A. 1. Burnazyan. Moscow, 
1972.
 
7 
4. Davydov, 0.V.Voyen.-ied, zb.. .No2 t1924i, p 59. 
5. 	 IKxneyeva, V. V.; andUshakov, A.,. *.RiTzhogichekive-.probleudaetrenixovannostj.- '$bysilalcgia. :2roblernk- Da~iietr nJ,!oscow, 1970, 
pp 127-133. 
6. 	 Panferbva , N. Ye. Giodlnamiya j serdechno-sosWdistaya sistema f"ypo­
dYnamia and Cardiovascular System"], Moseow, 1977. 
7. 	 Sinonenko, V. V. in o kosnicheskov. biologi ["Problems of Space
Biology"], Moscow, vol 13, 1969, pp 42-49 . 
8. 	 Ushakov, A. S.; Itrneyeva, N. V.; and Vitollo, A. S. in Fizioloicheskiv 
i klinicheskiye 2 adaptatsi cheloveka i zhivotnogo k gipertermiigipoksii i gipodinamil ["Physiological and Clinical Problems of Adaptation
of Man and Animals to Hyperthermia, Hypoxia and Hypodynamia"], Moscow, 
1975, pp 147-149.
 
9. 	 Fedorov, B. M. Emotsii ± serdecbnaya devatel'nost' ["Ekotions and Cardiac 
Activity"], Moscow, 1977. 
10. 	 Novelli, G. D. 'Meth. Biochem. Anal. , vol 2, 1958, p 189. 
11. 	Tucek, S. "Physiol. Bohamoslov., vol 13, 1964, pp 39-47. 
12. 	 Vlk, J., Tucek, S., Ibid., vol 10, 1961, pp 65-71. 
13. 	Zeleny, A-., 
Kozak, J., Nature, vol 181, 1958, pp 1340-1341.
 
Copyright Holder: "Patologicheskaya fiziilogiya i eksperimental'naya

terapiya", 1979
 
8 


Features of cholinergic cardia regulation under conditions of hypokinesia

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