The emotional effect of different applications of electrodes and the fixation for cariographic examination was investigated using guinea pigs. The effect of the stress is discussed in terms of heart rhythm and behavior

Mikiskova, H.

English

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THE EFFECT OF RESTRAINING ON THE HEART
RATE IN GUINEA PIGS
H. Mikiskovg.
Translation of "Vliv omebeni pohybu na sroeeni frekvenci morcat",
Activitas
Nervosa Superior, Vol. 10, No. 4, 1968, pp 382-388
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(NASA-11-76006) THE EFFECT OF RESTRAINING
	 N80-229E2
ON THE HEART RATE IN GUINEA PIGS (NationalAeronautics and Space Administration) 12 p
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	 CSCL 06C	 Unclas
G.3/51 47686
NATIONAL AERONAUTICS AND SPACE ADMINISTRATION
fi	 rr,,`t^, ` 'C4	 Washington, D. C.	 20546	 January, 1980
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1.	 Report
N^iS^A TM-76006
2. Government Accession No. 3.	 Rec' ipient's Cotalog No.
4.	 Title and 50fitle
The Effect of Restraining on the Heart` 5: Aarivary 1980
6.	 Performing Organisation CodeRate in Guinea Pigs
7. Authors) 8.	 Performing organization Report No.
H. , Mikiskova
10.	 Work Unit Ni)'.
11.	 Contract or Grant No.
9.	 Performing Organization Nome and Address NASW
SCITRAN	 I C:
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13.	 Type of Report and Period Coaired
Translation
1,2.	 Sonsoring A eney Nome and Address
W3tiona^ Aeronautics and Space Administration
14. Sponsoring Agency CodeWashington, D.C.	 20546
15. 'Svpplementary Notes
Translatign of t'Vliv omebeni Pohybu na sroeeni frekvenci
morc,a.t"
Activita§,Nervosa Superior, Vol. 10, No..4, 1968, , pp 382-388
16.	 Abstract
The electrocardiography of laboratory animal's is an electro--
physiological technique bbcoming of interest to the pharma-
cologists,and toxicologists for the followin^'reasons: 1.
It complements the neurophysical'methods of obtaining data
about the central nerve control of the
	
ve8etdtive functions;
2.	 It permits the study of the pharmdoodynamic effect on
excitable tissue whose cyclic changes.of.excitation,can be
often studied much easier than the changes in the central
nerve functions.
17. Key Words (Selected by Author(s)) 18.	 Oistribution Statement
Unclassified — Unlimited
19.	 Security Clossif. (of this report) 20.	 Seewrity Ciessif. (of this poyr} 21. 11-, of AepFr` 	 ! 2Y,	 f=;:	 w	 '
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THE EFFECT OF RESTRAINING ON THE HEART RATE IN GUINEA PIGS
H. Mikiskova
The electrocardiography of laboratory animals is an electro-
physiological technique becoming of interest to the pharmacologists
	
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and toxicologists for the following reasons:
1. First of all, it complements the neurophysical methods
of obtaining data about the central nerve control of the
vegetative functions;
2. It permits the: study of the pharmacodynamic effect on
excitable tissue whose cyclic changes of excitation can
s be often studied much easier than the changes in the
central nerve functions.
The basic information about the heart rhythm, i.e., the point
of origin of the heart excitation, rhythm regularity and mean heart
frequency is often more important for the quantitative evaluation of
y
the pharmacodynamic effects than other characteristics of the animal
cardiograms. A detailed study of other characteristics often may
help to analyze the mechanism of the effect of the materials (com-
pounds) under study, however. (Mikiskova and Mikiska, 1968).
During a regular activity the determination of the heart fre-
quency is quite unambiguous and independent of the location of the
electrodes, conductor system or technical parameters of the instru-
ment used. In spite of that, the data in the literature pertaining
to normal heart frequency for a certain animal species vary consider-
ably. Often the differences in factors such as age and emotional
state o.i' the animal tested are not considered and these may be very
important. We have systematically studied an effect of drugs on the
cardiogram of a guinea pig as affected by these factors.
This work evaluates the emotional effect asrelated to different
applications of electrodes and possibly fixation of the animal
ra
	
	 needed for a cardiographic examination. The study of electrocardio-
grams of guinea pigs in ontogenesis will be the subject of another
m
communication.
M. A guinea pig is one of the most quiet laboratory animals and
is, therefore, suitable for relatively easy ways to obtain long term
<_:
	
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and reasonably undisturbed bioelectric potentials (ECG, EEG, EMG,
etc.) in pharmacological and toxicological experiments. Many
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	methods of the electrocardiographic , registration still frequently
used with animals affect their emotional state and are not suitable,
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considering the current development of the electrophysiologic tech-
niques (e.g., application of needle electrodes). Some other methods,
such as ECGrin an unnatural fixation on the back, used by Bartmann
and Reinert (1952) are justified only for special experiments, such
as a thorough examination of all chest leads.
The use of light anesthesia (Lombard, 1952) or drastic res-
triction of the mobility of the animal (Pratt, 1938, Corwin et al,
1963) is necessary usually for a routine cardiography of smaller
rodents, such as mice, hamsters, rats, but it is considered unnecess-
ary for guinea pigs. The technique developed by Lukoschkova and
Thiessen (1954) whereby the guinea pig is held in hand during
registration may be suitable only for short term tests for orienta-
tion. A method due to Richtarik and Woolsley (1965) is more suitable
for ?gong term tests. The ECG is taken while the animal stands in a
normal position on four electrodes located on the bottom of a box
made from organic glass. The box restrict the mobility of the
animal. The most adequate, however, i,s the way to take ECG on an
animal which is unrestricted using radio telemetry or a flexible
cable. Such methods are still rather rare and so far as we know,
they have not been used for guinea pigs.
We took ECG on- unrestricted guinea pigs in our laboratory using
wire connections and radio telemetry and compared results obtained
on animals tied to a fixation table.
METHODOLOGY
The ECG of guinea pigs was registered by an electroencephalograph
(WTBG, Berlin) for one minute, one hour apart. The animals (males)
were all subject to 2 to 3 dry runs to get used to the test conditions.
All data about the age, weight of the animals as well as the number
2
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number and duration of the experiments are shown in pertinent tables
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'The following methods of registration were used:
1. Animals tied to the fixation table with abdomen down,
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	 ECG was taken using electrodes connected by means of radiotechnic
"crocodiles". The skin of the legs of the animals was defiled and
covered by electrocardiographic paste (Mikiska and Mikoskova, 1964).
2. Animals moving freely, the use of radiotelemetry. To
measure the potential, the electrodes used were in the form of a
silver plate 8mm diameter, located in a body cut from organic glass
(Figure 1). The electrodes were attached to the skin by means of
colodium. The conductivity is achieved by a layer of paste, the
wiring is connected by a nut. The electrodes were modified accord-
ing to a larger type used for ECG of p('aople=during work (Vodolarskiy
et al 1961, Mikiska, 1967). The best location of electrodes on
freely moving guinea pigs was-on-the vertex and the small of the
back. This way the shape of ECG does not differ from a VF and the
effect of electromyographic potential is present only when the move-
ments of the,animal are substantial.: The test is performed in a
quiet room and the animal remains in its own cage (without the top).
The electrodes are connected to a transmitter, fixed to the back.of
the guinea pig by means of leather loops attached to the upper
extremity and an elastic rubberband located under the abdomen. The
transmitter is a scaled down version of that used for a telemetric
ECG on humans (Mikiska, 1967, Mikiska and Hyska, 1967); the main
difference being smaller capacity electrolytic condensators and
lower voltage sources. The total mass of the transmitter was thus
reduced to 709. The schematics of the telemetric system, including
both transmitter and receiver, is included in our complete report
(Mikiskova and Mikiska, 1968).
3 Animals moving freely, the use of connection by a flexible
cable. The experiments were carried out in the same environment
and with the same electrodes as the telemetric experiments described
above. The electrodes, however, were connected to the instrument
3
directly with a two-line cable about 1 meter long. The results of
`	 the experiments with different methods are in Graph 1 and Table 1.
r
In the case of fixed animals, the heart frequency remains remark-
btCL ly ,s able, during six hours the drop in the heart frequency for
the younger age group is on the average 1.9%. In the case of
younger animals moving freely, the heart frequency slows down gradually,
especially when the cable connection is used, the reduction is up to
29.2%. The changes in ,the older group and similar; however, the
difference between the final and initial values in the case of freely
moving animals is lower (on the average 21.2%).
Initial values of heart frequency in all experimental situations
are lower for the older animals. When the animals move freely and
connection is done by the cable, the frequencies for both age groups
come close during the 5th and 6th hour.
The behavior of the older age group of guinea pigs is shown
in Graph 2. On the right side of the graph, results from 17 exper-
iments with 6 animals moving freely for 4 hours and fixed to a table
for subsequent 2 hours are plotted. ECG was registered by means of
a flexible cable. The heart frequency, reduced in average by 18%
at the end of the 4th hour, returns immediately after the fixation
to the initial value and remains there until the end of the experiment.
In the Table 1', a pO Craphs 1-2 ' Q the values are only average for
the individual age groups and experimental situations. We could
not find any significant differences between Andividuals during the
experiments even after three repetitions.
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	 DISCUSSION
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of fixed guinea pigs
those found in other
The slow down in fre
is much more pronounced
nt by the thin cable
The initial values of heart frequency
found in our experiments are quite close to
works (e.g., Richtarik and Wools2 ey, 1965).
quency experienced in freely moving animals
for guinea pigs connected with the instrume
4
than in the case of animals with telemetric transmitter. Possibly
the effect of the instrument, ''its way of installation and its
weight has to be considered,: The use of an implanted transmitter
may produce better results.
We obtained similar rc:;zults with freely moving rabbits, and
Pound considerable slow dow;z 3,n he6rrt beats, sometimes down to 150
beats per minute. For fixed tlrabbits Haberland and Regoeczi (1963)
report the minimum of 200 beats per minute, a value similar to that
reported in other works.
The slow down in heart frequency of freely moving animals
under minimum values determined by a usual method and reported in
test books was demonstrated by Essler and Folk (1961, 1962) , by a
series of experiments with a dog and a cat isolated in a sound-
proofed room for several days, using telemetry. The authors did not
find a similar effect when experimenting with a rabbit._ Our
experiments summed up in the right part of Graph 2 show that the fixa-
tion of the guinea pig is the main factor which causes the relatively
constant heart frequency when measuring it the usual way, i.e.,
with the animal tied down. The value obtained in this manner is
quite reproducible and, therefore, it is suitable for the use in
applied research in spite of the fact that it is not "basal".
During the measurement of ECG in freely moving guinea pigs,
the heart rate decreases during the experiment but the change occurs
continuously and regularly; one can depend on it while designing an
experiment. As an example, we can give the experiments with tele-
metric ECG during the exposure to carbon disulphide vapors (Mikiskovd
and Mikiska, 1968). In some experiments the slow down of the heart
beat can be utilized, e.g., analeptics even at low dosage will
likely prevent it.
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A guinea pig, unlike the smaller laboratory rodents, does not
have pronounced switch from an activity to a deep sleep (Nicholls,
1922, Schwarz and Bickford, 1957, Veselovskg, 1964, and Mikiska,
5
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1965). Very likely this can be related to our finding that during
the measurement of the heart activity of guinea pigs over a period
of several hours, no significant variations in frequency are
observed. As an example of such a measurement are results in Grapb
3. In this graph several individual measurements of heart frequency
done telemetrically on free moving guinea pigs of the weight range
450 to 580 g are depicted. For comparison a time dependent tele-
metric data obtained on a mouse by Ko and Neuman (196,") are shown.
TABLE 1
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DOW, 0d zt, <Atltu Pckt: m (hod.) z Itohitit 1 P 't
ro:-u^..E cituaa itiod—lSchyba ;1Z
^i 0 1 I ^_ 41	 3 L I	 6 prararu i kwu I•	 '
au mo.v s.ai
1 It:pot"UmA ke stolku 362 300 360 337 355 354 455 X1,1 % 28 6
V01a3 pohybUvi
9 (s vysi:acont) 20S 352 330 325 320 320 2,0 % 7 7
volo5 pohyblivb o
to (spoioai'A bUkcm) '343 290 270 1 265 251. 240 243 X2,0 °o I	 18 S
Star3i rao:cata^
o	 gait kq sto	 m 323 ( 321 316 300 309 311 1304 —1,8 0,/ IS	 3
1!
v;
1,;,  viola + pohyb:ivb{a ^^ Pa° r) 301 275, .'^.^0 9;0 272 200 :1 04 x-2,3 Oro 28 ^	 S
S vo:r6 ponyblivd f,Oat kal,"-cm) :37 274 12J5 1 251 244 1242 234 12,2 % 1S	 3
7
R 1,
^'	 /1^	 i — v5i 2-4 mucloe, vt}^a 3:A—SSO ^. `+ v3lz 12-15'm3c:ct^, vfSa 500-1100 ^.	 ..
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	 Key: 1--Time from start of experiment (hrs); 2--Relative mean
error; 3--Number; 4--Experiments; 5--Animals; 6--Experimental
situation; 7--Younger guinea pigs (1); 8--Fixed to a table; 9--
t Freely moving (with a transmitter); 10--Freely moving (with a
cable); 11--Odder guinea pigs (2),; 12--Fixed to a table; 13--
Freely moving (with a transmitter); 14--Freely moving (with a
cable); 15--Notes (1) Age 2-4 months, weight 330 to 5808; (2)
Age 12-18 months, weight 800 to 1100 g
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Figure 1. Transmitter and piak-up electrodes for
the telemetric ECG of animals (scale in cm).
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Graph 1: Average heart frequency of guinea pigs in three different
situations:
A - Animals fixed to a table
B - Animals freely moving with a transmitter affixed to the back
C - Animals freely moving connected to the instrument by a
flexible cable'
X--axis: Time from the start of the experiment
Y--axis: Heart frequency (in logarithmic scale)
circles - Average values of the heart frequency measured hourly
thin lines - Average ± mean error of average
^wwni r "INC,i
k I	 3 < 5 i	 ^ 1 2	 < S B
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Graph 2: Right part - Average heart frequency of guinea pigs (800
to 1100 g) freely moving for 4 hours, then fixed to a
table for 2 hours;
Left part - 6-hour experiments for animals of the same age
fixed (A) and freely moving (C). X and Y axis the same as
in Graph 1.
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1 1 1	 ,	 I	 ' i	 i	 1	 1	 1' 1400- ..
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14 1A	 M	 20	 u h
400
1Z	 14 h
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Graph 3: Comparison of individually measured changes in tele-
metric ECG of guinea pigs (full line, our own results)
and,,of mice (broken line, Yo and Neuman., 1967)
X--axis: The `hour of the dayI
Y--axis: Heart frequency (in the logarithmic scale)
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References
Bartman, K., Reinert, H. Extremity and Breast Wall EKG of a
non-anethtisized Guinea Pig, Naunyn-Schmiedeberg's Arch.`exp. Path.
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Corwin, A. H., Dukes-Dobos, F. N., Hamberger, M.: Bio-assay
of Food Allergens. II. Food-induced Reactions of the Heart Rate
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Essle:rs>, W. O.,Folk, G.E. Jr.: Determination of Physiological
Rhythms o'f Unrestrained Animals by Radio Telemetry. Nature (Lond.),
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Essler, W. 0. Folk, G. E,Jr.: A Method of Determining True
Resting Heart Rate of Unrestrained Mammals by Radio Telemetry.
Anim. Beha y .,10, 1952, 	 168 -170.
Haberland, G., RegoE^`czi, E.: The Constant Nature of the Heart
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ii% l
Ko, W. H. Neuman, MA /'', R.: Implant Biotelemetry and"Microelectro-
nics. Science, 1967, 1,56,,"351-360.=
Lombard, E. A.: Electrocardiograms of Small Mammals, Amer.
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Mikiska, A.: Short-distance Radio Telemetry of Biopotentials in
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25 3 1968: ;81-105.
9
,.rte_
tM
t
E !
	
	 Nicholls, E B-	 A Stadlf of the Spontaneous Activity of the
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*GHPChP - The Institute of Work Hygiene of the Chemical Industry.
10


The effect of restraining on the heart rate in guinea pigs

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