330
Bulletin of Experimental Biology and Medicine, Vol. 157, No. 3, July, 2014 GENERAL PATHOLOGY AND PATHOPHYSIOLOGY
Depolarization of Atrial Epicardium near Pulmonary Veins Orifices in Hypertensive ISIAH Rats S. L. Smirnova, M. P. Roshchevskii, and I. M. Roshchevskaya Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 157, No. 3, pp. 305-308, March, 2014 Original article submitted March 2, 2013 The formation of early activation regions was demonstrated in the area of the pulmonary vein orifice in hypertensive rats. The appearance of early activation zones on the dorsal side of the left atrium near the pulmonary veins simultaneously with the sinoatrial node in rats with arterial hypertension indicates the possibility of ectopic foci formation in the area of pulmonary vein sleeves. Key Words: depolarization; atria; stress-induced hypertension; rats Atrial fibrillation (AF) is one of the most often forms of arrhythmias in clinical practice [6]. There are two theories of AF genesis: formation of ectopic foci and re-entry. Earlier studies of the area of pulmonary veins revealed ectopic activity that can lead to AF [11]. In the area of the pulmonary veins, ectopic foci arise generally near the superior pulmonary veins, rarely near the inferior pulmonary veins [3]. The structure of the pulmonary veins and the posterior wall of the left atrium, the site of the pulmonary venous confluence to the left atrium and the posterior wall of the left atrium, promotes AF [1]. Arterial hypertension can provoke AF in humans [2]. Hypertensive rat strains may serve as experimental models for the study of electrical activity of the hypertrophied heart. ISIAH rats were breed by selection for studies of the effects of genetic predisposition to emotional stress during the development of stable hypertension [4]. Signs and symptoms characteristic of human hypertensive disease are well reproduced in this model [14]. It remains unclear whether hypertension affects the dynamics of propagation of the atrial excitation wave. The sequence of depolarization the myocardial Laboratory of Comparative Cardiology, Komi Science Center, Ural Division of the Russian Academy of Sciences, Syktyvkar, Russia. Address for correspondence: [email protected]. S. L. Smirnova
sleeves of the pulmonary veins in hypertrophied myocardium has not been studied. Here we studied propagation of the excitation wave fronts in the atrial epicardium near the pulmonary veins orifice in rats with stress-induced arterial hypertension.
MATERIALS AND METHODS The propagation of excitation wave fronts over left atrial epicardium near the pulmonary vein orifice was studied by the method of cardioelectrochronotopography in hypertensive ISIAH rats (inherited stressinduced arterial hypertension) bred at the Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences [5,14]. The animals were kept in a vivarium. The rats were anesthetized with urethane (1 mg/kg, intramuscularly). During the experiment, systolic pressure in rats was 190±17 mm Hg. Tracheotomy was performed before chest opening, and animals were artificially ventilated. The rate and depth of breathing was determined individually for each animal. After the chest was opened and the heart was exposed, multichannel surface electrodes were applied to the atrial epicardium and unipolar electrograms (Eg) was synchronously recorded from 32 electrodes positioned on both atria. ECG in limb leads was recorded synchronously with epicardial Eg.
0007-4888/14/15730330 © 2014 Springer Science+Business Media New York
S. L. Smirnova, M. P. Roshchevskii, and I. M. Roshchevskaya
The obtained data were processed using Kardioinform system [7]. The front of excitation wave at each lead was recorded by the minimum of the first time derivative of potential. After the experiment, the pattern was reconstructed by the location of points and time, and then a chronotopographic map was constructed. The time was relative to the beginning of the P wave. Data are presented as arithmetic mean±standard deviation, maximum, and minimum. The significance of differences was assessed by the Mann–Whitney U test.
RESULTS In the area of superior vena cava orifice (area of the sinoatrial node) in the right atrium, negative deep initial atrial QSa complexes were registered on the ventral surface in hypertensive rats (Fig. 1, a; Table 1). From this area, excitation wave uniformly spreads in the epicardium of the right atrium to the dorsal side and interatrial septum. Biphasic Rsa complexes were detected in the area of the projection of the interatrial septum on atrial epicardium. The depolarization front migrates from the right atrium to the dorsal side of the left atrium in the area of pulmonary vein sleeves 8±3 msec after the start of the excitation in the region of the superior vena cava. On the ventral surface of the left atrium close to the right atrium, biphasic unipolar rSa complexes were registered. As the front of the excitation wave moved from the ventral surface of the left appendage to the base of the dorsal surface in the area of the drainage of pulmonary veins, Ra and rRa waves were transformed
331 into Rsa. The time of depolarization of the epicardium of pulmonary veins orifices in ISIAH rats is 6.5 msec. This pattern of excitation wave propagation is characteristic of 73% hypertensive rats. In 27% hypertensive rats, in the epicardium of the area of the pulmonary veins sleeves, the regions of early activation were revealed simultaneously (2-3 msec or later) in the area of the sinoatrial node (Fig. 1, a; Table 1), where two-phase unipolar rSa complexes were registered. From the zones of early activation in the epicardium of the pulmonary veins sleeves, the excitation wave spreads to the left atrial appendage and interatrial septum and merges with the depolarizing wave front moving from the right atrium. Heterogeneity of propagation of the excitation wave in the area of the pulmonary vein sleeves in the left atrium was observed. The time of depolarization of the epicardium of pulmonary veins orifices in ISIAH rats is 2 msec. In hypertensive rats, the regions of early activation arise on the epicardium in the area of the pulmonary vein sleeves, which leads to non-uniform atrial excitation. The study of intracellular action potentials revealed autonomic pacemaker-like activity of cells in the area of the pulmonary vein sleeves activity, but not in adjacent muscle cardiomyocytes [10]. The presence of pacemaker-like cells near the pulmonary vein can determine the formation of ectopic foci and AF [13]. Pulmonary veins are considered as the source of ectopic activity triggering AF [9]. Clinical studies have shown a direct correlation between the increase in the size of the left atrium and the risk of paroxysmal atrial
Fig. 1. Propagation of the excitation wave fronts over atrial epicardium in rats with stress-induced arterial hypertension. a) Without regions of early activation in the area of the pulmonary vein sleeves (73% of hypertensive rats), b) with regions of early activation the area of the pulmonary vein sleeves (27% of hypertensive rats). RA: right atrium; LA: left atrium; SVC: superior vena cava; IVC: inferior vena cava; PV: pulmonary veins.
332
Bulletin of Experimental Biology and Medicine, Vol. 157, No. 3, July, 2014 GENERAL PATHOLOGY AND PATHOPHYSIOLOGY
TABLE 1. The Shape of Epicardial Eg and Time of Depolarization in Different Atrial Zones of ISIAH Rats
Parameter
Rats without regions of early activation in the pulmonary vein sleeve area (73%; 8/11)
Rats with regions of early activation in the pulmonary vein sleeve area (27%; 3/11)
0
0
8.4±3.4*
5.7±0.7*
6.5±0.4*
2.0±0.5*
Eg in the area of sinoatrial node Time of depolarization of the area of sinoatrial node, msec
Eg in the area of atrial septum Transit time of the excitation wave from the right atrium to the dorsal side of the left atrium, msec
Eg at the site of the pulmonary venous confluence to the left atrium Time of depolarization at the site of the pulmonary venous confluence to the left atrium, msec
Note. Data are presented as mean±standard deviation (maximum, minimum). *p
Bulletin of Experimental Biology and Medicine, Vol. 157, No. 3, July, 2014 GENERAL PATHOLOGY AND PATHOPHYSIOLOGY
Depolarization of Atrial Epicardium near Pulmonary Veins Orifices in Hypertensive ISIAH Rats S. L. Smirnova, M. P. Roshchevskii, and I. M. Roshchevskaya Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 157, No. 3, pp. 305-308, March, 2014 Original article submitted March 2, 2013 The formation of early activation regions was demonstrated in the area of the pulmonary vein orifice in hypertensive rats. The appearance of early activation zones on the dorsal side of the left atrium near the pulmonary veins simultaneously with the sinoatrial node in rats with arterial hypertension indicates the possibility of ectopic foci formation in the area of pulmonary vein sleeves. Key Words: depolarization; atria; stress-induced hypertension; rats Atrial fibrillation (AF) is one of the most often forms of arrhythmias in clinical practice [6]. There are two theories of AF genesis: formation of ectopic foci and re-entry. Earlier studies of the area of pulmonary veins revealed ectopic activity that can lead to AF [11]. In the area of the pulmonary veins, ectopic foci arise generally near the superior pulmonary veins, rarely near the inferior pulmonary veins [3]. The structure of the pulmonary veins and the posterior wall of the left atrium, the site of the pulmonary venous confluence to the left atrium and the posterior wall of the left atrium, promotes AF [1]. Arterial hypertension can provoke AF in humans [2]. Hypertensive rat strains may serve as experimental models for the study of electrical activity of the hypertrophied heart. ISIAH rats were breed by selection for studies of the effects of genetic predisposition to emotional stress during the development of stable hypertension [4]. Signs and symptoms characteristic of human hypertensive disease are well reproduced in this model [14]. It remains unclear whether hypertension affects the dynamics of propagation of the atrial excitation wave. The sequence of depolarization the myocardial Laboratory of Comparative Cardiology, Komi Science Center, Ural Division of the Russian Academy of Sciences, Syktyvkar, Russia. Address for correspondence: [email protected]. S. L. Smirnova
sleeves of the pulmonary veins in hypertrophied myocardium has not been studied. Here we studied propagation of the excitation wave fronts in the atrial epicardium near the pulmonary veins orifice in rats with stress-induced arterial hypertension.
MATERIALS AND METHODS The propagation of excitation wave fronts over left atrial epicardium near the pulmonary vein orifice was studied by the method of cardioelectrochronotopography in hypertensive ISIAH rats (inherited stressinduced arterial hypertension) bred at the Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences [5,14]. The animals were kept in a vivarium. The rats were anesthetized with urethane (1 mg/kg, intramuscularly). During the experiment, systolic pressure in rats was 190±17 mm Hg. Tracheotomy was performed before chest opening, and animals were artificially ventilated. The rate and depth of breathing was determined individually for each animal. After the chest was opened and the heart was exposed, multichannel surface electrodes were applied to the atrial epicardium and unipolar electrograms (Eg) was synchronously recorded from 32 electrodes positioned on both atria. ECG in limb leads was recorded synchronously with epicardial Eg.
0007-4888/14/15730330 © 2014 Springer Science+Business Media New York
S. L. Smirnova, M. P. Roshchevskii, and I. M. Roshchevskaya
The obtained data were processed using Kardioinform system [7]. The front of excitation wave at each lead was recorded by the minimum of the first time derivative of potential. After the experiment, the pattern was reconstructed by the location of points and time, and then a chronotopographic map was constructed. The time was relative to the beginning of the P wave. Data are presented as arithmetic mean±standard deviation, maximum, and minimum. The significance of differences was assessed by the Mann–Whitney U test.
RESULTS In the area of superior vena cava orifice (area of the sinoatrial node) in the right atrium, negative deep initial atrial QSa complexes were registered on the ventral surface in hypertensive rats (Fig. 1, a; Table 1). From this area, excitation wave uniformly spreads in the epicardium of the right atrium to the dorsal side and interatrial septum. Biphasic Rsa complexes were detected in the area of the projection of the interatrial septum on atrial epicardium. The depolarization front migrates from the right atrium to the dorsal side of the left atrium in the area of pulmonary vein sleeves 8±3 msec after the start of the excitation in the region of the superior vena cava. On the ventral surface of the left atrium close to the right atrium, biphasic unipolar rSa complexes were registered. As the front of the excitation wave moved from the ventral surface of the left appendage to the base of the dorsal surface in the area of the drainage of pulmonary veins, Ra and rRa waves were transformed
331 into Rsa. The time of depolarization of the epicardium of pulmonary veins orifices in ISIAH rats is 6.5 msec. This pattern of excitation wave propagation is characteristic of 73% hypertensive rats. In 27% hypertensive rats, in the epicardium of the area of the pulmonary veins sleeves, the regions of early activation were revealed simultaneously (2-3 msec or later) in the area of the sinoatrial node (Fig. 1, a; Table 1), where two-phase unipolar rSa complexes were registered. From the zones of early activation in the epicardium of the pulmonary veins sleeves, the excitation wave spreads to the left atrial appendage and interatrial septum and merges with the depolarizing wave front moving from the right atrium. Heterogeneity of propagation of the excitation wave in the area of the pulmonary vein sleeves in the left atrium was observed. The time of depolarization of the epicardium of pulmonary veins orifices in ISIAH rats is 2 msec. In hypertensive rats, the regions of early activation arise on the epicardium in the area of the pulmonary vein sleeves, which leads to non-uniform atrial excitation. The study of intracellular action potentials revealed autonomic pacemaker-like activity of cells in the area of the pulmonary vein sleeves activity, but not in adjacent muscle cardiomyocytes [10]. The presence of pacemaker-like cells near the pulmonary vein can determine the formation of ectopic foci and AF [13]. Pulmonary veins are considered as the source of ectopic activity triggering AF [9]. Clinical studies have shown a direct correlation between the increase in the size of the left atrium and the risk of paroxysmal atrial
Fig. 1. Propagation of the excitation wave fronts over atrial epicardium in rats with stress-induced arterial hypertension. a) Without regions of early activation in the area of the pulmonary vein sleeves (73% of hypertensive rats), b) with regions of early activation the area of the pulmonary vein sleeves (27% of hypertensive rats). RA: right atrium; LA: left atrium; SVC: superior vena cava; IVC: inferior vena cava; PV: pulmonary veins.
332
Bulletin of Experimental Biology and Medicine, Vol. 157, No. 3, July, 2014 GENERAL PATHOLOGY AND PATHOPHYSIOLOGY
TABLE 1. The Shape of Epicardial Eg and Time of Depolarization in Different Atrial Zones of ISIAH Rats
Parameter
Rats without regions of early activation in the pulmonary vein sleeve area (73%; 8/11)
Rats with regions of early activation in the pulmonary vein sleeve area (27%; 3/11)
0
0
8.4±3.4*
5.7±0.7*
6.5±0.4*
2.0±0.5*
Eg in the area of sinoatrial node Time of depolarization of the area of sinoatrial node, msec
Eg in the area of atrial septum Transit time of the excitation wave from the right atrium to the dorsal side of the left atrium, msec
Eg at the site of the pulmonary venous confluence to the left atrium Time of depolarization at the site of the pulmonary venous confluence to the left atrium, msec
Note. Data are presented as mean±standard deviation (maximum, minimum). *p
