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Comparison of propagation of atrial excitation with the cardiopotential distribution on the body surface of hypertensive rats/Hipertansif sicanlarda vucut yuzeyinde kardiyopotansiyel dagilimi ile atriyal uyarim yayilmasinin karsilastirilmasi.


In order to research development mechanisms of myocardial hypertrophy of different genesis, experimental animal models such as hereditary hypertensive rats, spontaneously hypertensive rats (SHR line), stress-induced arterial hypertension rats (ISIAH line), and experimentally created specimens are used. An increase of P-wave duration is revealed in the electrocardiogram (ECG) limb leads in hypertensive rats (ISIAH line), (1).

In normotensive rats, the excitation wave spreads along the atrial epicardium from the pacemaker region successively to the right and left atrium (2). In human, arterial hypertension leads to the thickening of the left atrium, a change in conduction velocity of excitation, an increase in P-wave amplitude in the ECG, and stimulates the development of atrial fibrillation (3). The ECG in standard leads is not informative enough for estimating initial phase of atrial depolarization (4). Recordings and analyses of the cardioelectric field on the body surface reveal electrical atrial activity during early depolarization, prior to the formation of the P-wave in the EC[G.sub.II] (5).

The pattern of the sequence of atrial depolarization and regularities of the reflection of excitation on BSPM in hypertensive rats is not described.

This research was aimed at studying the sequence of depolarization along the atrial epicardium and formation of the cardio electric field on the body surface of hypertensive rats.



Studies were carried out on three-month-old (n=11), male stress-induced arterial hypertension rats (line ISIAH), anesthetized with urethane (1 mg/kg, im). ISIAH rats were selected for studying the influence of genetic predisposition to emotional stress in forming stable arterial hypertension in the Institute of Cytology and Genetics of the Siberian Division of the Russian Academy of Sciences. Hypertensive ISIAH rats can be good experimental specimens for studying the peculiarities of the heart's electrical activity in hypertension. These are characterized by high arterial pressure: 160-166 mm of mercury in males and 143149 mm of mercury in females. The signs and symptoms of hypertension in human beings are well reproduced in such rats (6).

During the experiment, the systolic pressure in ISIAH rats formed 190 [+ or -] 17 mm of mercury. Heart mass in ISIAH rats was recorded at 1.2 [+ or -] 0.07 g; body mass measured 295 [+ or -] 21 g. All animals received care in compliance with the principles of laboratory animal care formulated by the National Society for Medical Research and the Guide for the Care and Use of Laboratory Animals.

Body surface potential mapping and experimental protocol

Body surface potential mappings (BSPM) were simultaneously recorded from 32 subcutaneous needle electrodes (registering surface-0.06 [cm.sup.2]), uniformly distributed on the torso surface of rat (from the basis of the ears to the last rib). Before opening the thorax, we conducted a tracheotomy, and artificial respiration was also performed. The frequency and depth of breathing were selected individually for each animal. The rats' body temperature was recorded at 37[degrees]C. After opening the thorax and cutting the pericardium, by using multipolar electrode with 32 leads (registering surface -0.004 [cm.sup.2]) unipolar epicardial electrograms (EG) were recorded from both atria in the same animals.


Simultaneous data acquisition was done by means of a custom-designed mapping system (16 bits; bandwidth 0.05 to 1000 Hz; sampling rate 4000 Hz) (7).

Unipolar electrograms and ECGs were recorded in reference to Wilson's central terminal. By unipolar ECGs from the body surface isopotential mappings were constructed. Sequence of spreading of the excitation wave was constructed through the first temporal derivative of epicardial EG. BSMP and sequence of epicardial depolarization were compared relative to R-peak in the ECGjj in the limb leads.

The beginning of the P-wave was defined as the junction between the isoelectric line and the beginning of the P-wave deflection and the end of the P-wave as the junction between the end of the P-wave deflection and the isoelectric line. The beginning of inversion of BSPM is the beginning of changing mutual positions of zones of positive and negative cardiopotentials. Duration of inversion on BSPM is the time during which the inversion occurs.

The data processing was carried out using the software of our development (7).

Statistical analysis

Data were analyzed using Statistica software version 6.0 for Windows statistical package (StatSoft, Inc., Tulsa, OK, USA). All results were expressed as mean [+ or -] standard deviation. Statistical analysis was performed using an independent samples t-test. Differences were considered to be statistically significant if the p value was <0.05.


Body surface potential distribution

BSPM in the cranial zone of positive potentials, which occupy the largest section, were conducted on the ventral and dorsal sides of body surfaces, and BSPM in the caudal zone of negative potentials--on the dorsal side (Fig. 1A, Table 1) in 73% of the rats with arterial hypertension before the [P.sub.II]-wave deflection appeared. The positive BSPM zone shifts caudally, while the negative zone shifts cranially. Inversion occurs. Changes in mutual positions of positive and negative zones terminate when the initial stages of the [P.sub.II]-wave are shaped. During ascending and descending phases of the [P.sub.II]-wave, the BSPM zone of positive cardiopotentials occupies the caudal part, whereas the zone of negative cardiopotentials takes up the cranial part of the body surface, and this location does not change up to the end of atrial depolarization.

On BSPM of 27% of ISIAH rats before the beginning of the [P.sub.II]-wave, the zone of positive potentials is formed cranially, the zone of negative potentials-caudally. It coincides with the beginning of atrial depolarization. Mutual positions of BSPM positive and negative potentials occur before the beginning of the [P.sub.II]-wave as well as in 73% of ISIAH rats (Fig. 2A, Table 2).

In 27% of ISIAH rats, the positive potential zone of BSPM is located laterally left on the dorsal and ventral sides, whereas the negative potential zone is located laterally right. During the ascending and descending phases of the [P.sub.II]--wave, the zone positions do not change any more. The positive potential area of BSPM is situated caudally, whereas the negative potential area is located cranially.

Epicardial depolarization

In 73% of rats, the excitation wave spreads along the epicardium from the sinus node region, located in the superior vena cava (SVC) (Fig. 1B, Table 2). From the sinus node, the depolarization wave, rounding the SVC, passes to the right atrium (RA); first, it activates the upper part of the appendage, and then the front spreads evenly, depolarizing the middle and lower parts of the RA appendage on the ventral side. After the ventral surface has been activated, the excitation wave passes to the dorsal side, where the upper part of the appendage is depolarized first in the inferior vena cava, and then in the middle and lower parts. The excitation wave spreads to the left atrium (LA) over the left auricle to the upper and lower parts of the interatrial septum. Auricular excitation terminates on the dorsal side of the LA.


In 27% of hypertensive rats, early excitation areas are formed simultaneously along the epicardium in the PV sleeves (or 2 ms later), and in the sino-atrial node area simultaneously (Fig. 2B- Table 2). From the early activation area on the epicardium of PV sleeves, the excitation wave spreads to the left atrial appendage and interatrial septum, and meets with the depolarization front, moving from the right atrium. We can observe heterogeneous propagation of the excitation wave in the PV sleeves of the left atrium.



On the body surface of 27% of stress-induced arterial hypertension rats (line ISIAH) during atrial depolarization after inversion, the zone of positive cardiopotentials is situated laterally left on the dorsal and ventral sides, whereas the zone of negative cardiopotentials is located laterally right. It reflects the formation of two early activation zones on the epicardium in the sino-atrial node area and in PV return to the left atrium.

In normotensive rats, the excitation wave along the epicardium spreads successively from the sino-atrial node area, located in the upper vena cava. The excitation wave moves from the right to the left atrium in the posterior part of the interatrial septum (5). Histologically speaking, internodal conduction tracts are shown in the composition of the interatrial septum (8, 9). In 73% of hypertensive rats, the excitation wave spreads from the right to the left atrium along the anterior and posterior part of the interatrial septum. The propagation of the excitation wave along the epicardium from the right to the left atrium in normotensive and hypertensive rats (5) is probably connected with the position of predominant conduction tracts.

In 27% of hypertensive rats, early excitation areas are formed on the epicardium in the PV sleeves. This results in changes to the total picture of excitation propagation along the atria. In normotensive rats, the excitation wave spreads unidirectionally along the epicardium in pulmonary venous return to the left atrium (5).

Studies of intracellular action potentials in PV sleeves have revealed that cells can act as an independent accessory pacemaker, whose effects will not spread to adjoining muscular cardiomyocytes (10). Pacemaker-like cells in PVs can result in wandering focus and atrial fibrillation (11). Clinical studies have shown the direct dependence between the increase in the size of the left atrium under hypertrophy and the risk of developing paroxysmal fibrillation in human beings (12, 13).

The formation of early activation zones in PVs of rats with arterial hypertension testifies to possible wandering focus in the myocardium of PV sleeves. Stress-induced hypertension results in actual risks of atrial arrhythmias, which originate at the base of the PVs.

The formation of early activation zones in PVs of rats with arterial hypertension testifies to possible wandering focus in the myocardium of PV sleeves. Stress-induced hypertension results in actual risks of atrial arrhythmias, which originate at the base of the PVs.

Study limitations

The most important limitation of our study was the sample size. We would perform our experiments in a larger population to increase the statistical power of the study.


In rats with arterial hypertension, two early depolarization zones are revealed in the sinus node area and in the PV return to the left atrium, projected on body surface potential mappings by mutual positions of negative and positive potential zones.

Conflict of interest: None declared.

Authorship contributions: Concept--M.R., L.I.; Design--S.S.; Supervision--M.R., I.R., L.I.; Resources--M.R., I.R., L.I.; Material--S.S., A.M.; Data collection&/or Processing--S.S, I.R.; Analysis &/or Interpretation--S.S.; Literature Search--S.S.; Writing--S.S., I.R.; Critical review--S.S., I.R.; Other--S.S., L.I., A.M., M.R., I.R.


The studies were done with the support of the scientific school of academician M. P. Roshchevsky, Program Presidium RAS "Fundamental Sciences for Medicine", integration project on the program of the Presidium of the Urals Division, RAS, jointly with the Siberian Branch, RAS, Grant Proposal Taiwan Russian Research Cooperation RFBR 09-04-92011-HHC_a.


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(7.) Roshchevsky MP, Arteeva NV, Kolomeyets NL, Antonova NA, Kambalov MY, Shmakov DN, et al. The system "Cardioinform" for visualization and analysis of the heart electric field. Med Academic J 2005; 5: 74-9.

(8.) Emberson JW, Challice CE. Studies on the impulse conducting pathways in the atrium of the mammalian heart. Am Heart J 1970;79: 653-67. [CrossRef]

(9.) Ayettey AS, Navaratnam V, Yates RD. Ultrastructure of the internodal myocardium in the rat. J Anat 1988; 158: 77-90.

(10.) Cheung DW. Electrical activity of the pulmonary vein and its interaction with the right atrium in the guinea-pig. J Physiol 1981; 314: 445-56.

(11.) Jais P Haissaguerre M, Shah DC, Chouairi S, Gencel L, Hocini M, et al. A focal source of atrial fibrillation treated by discrete radiofrequency ablation. Circulation 1997; 95: 572-6.

(12.) Henry WL, Morganroth J, Pearlman AS, Clark CE, Redwood DR, Itscoitz SB, et al. Relation between echocardiographically determined left atrial size and atrial fibrillation. Circulation 1976; 53: 273-9.

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Svetlana Smirnova, Lyudmila Ivanova [1], Arkady Markel [1], Irina Roshchevskaya, Michail Roshchevsky

Laboratory of Comparative Cardiology, Komi Science Centre, Russian Academy of Sciences, Syktyvkar, Komi [1] Siberian Division, Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk--Russia Federation

Address for Correspondence/Yazisma Adresi: Svetlana Smirnova M.D, 167982, Kommunisticheskaya, 24, Syktyvkar, Komi-- Russia Federation

Phone: +7 8212 391451 Fax: +7 8212 391451 E-mail:

doi: 10.5152/akd.2012.060
Table 1. Time characteristics of BSPM and ECGM of rats of ISIAH
line during atrial depolarization

Variables (ms) Groups of rats * p

 73% of rats (8/11) 27% of rats (3/11)

Beginning of 66.8 [+ or -] 5.7 68.5 [+ or -] 6.1 0.685
 inversion on
Duration of 7.7 [+ or -] 1.9 3.9 [+ or -] 0.1 0.011
 inversion on
Beginning of 59.1 [+ or -] 7.2 64.5 [+ or -] 6.0 0.284
Peak of 53.8 [+ or -] 7.0 58.0 [+ or -] 5.6 0.378
End of P-wave 46.5 [+ or -] 7.0 51.7 [+ or -] 6.8 0.298
Total duration 16.7 [+ or -] 4.5 14.2 [+ or -] 0.7 0.383
 of P-wave

Data are presented as mean [+ or -] SD

* independent samples t-test

BSPM--body surface potential mapping, ECG--electrocardiogram,
ISIAH--stress-induced arterial hypertension rats

Table 2. Form of epicardial EG and time of depolarization in
the area of the sinus node and the area of pulmonary veins drain
into the left atrium in rats of ISIAH line

Number of rats EG in the area EG in the area
 of the sinus node of falling
 pulmonary veins to
 the left atrium

73% of rats (8/11) [??] [??]
27% of rats (3/11) [??] [??]

Number of rats Sinus node Depolarization of
 depolarization, ms the area of falling
 pulmonary veins to
 the left atrium, ms *

73% of rats (8/11) 0 6.5 [+ or -] 0.4
27% of rats (3/11) 0 2.0 [+ or -] 0.5

Data are presented as mean [+ or -] SD

* independent samples t-test (p<0.001)

EC--electrogram, ISIAH--stress-induced arterial hypertension rats
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Article Details
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Title Annotation:Original Investigation/Ozgun Arastirma
Author:Smirnova, Svetlana; Ivanova, Lyudmila; Markel, Arkady; Roshchevskaya, Irina; Roshchevsky, Michail
Publication:The Anatolian Journal of Cardiology (Anadolu Kardiyoloji Dergisi)
Article Type:Report
Date:May 1, 2012
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