Transmural dispersion of refractoriness and conduction velocity is associated with heterogeneously reduced connexin43 in a rabbit model of heart failure

Wiegerinck, Rob F.; Veen, Toon A.B. van; Belterman, Charly; Schumacher, Cees A.; Noorman, Maartje; Bakker, Jacques M.T. de; Coronel, Ruben

doi:10.1016/j.hrthm.2008.04.026

Cited by 58 publications

(56 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We conclude that spatial heterogeneity of the APD restitution, created with regional elevation of [K ϩ ]o, can lead to AP instability, 2:1 block, and reentry induction. restitution heterogeneity; regional perfusion; optical mapping THE STATIONARY AND DYNAMIC heterogeneities of electrophysiological properties of cardiac tissue play a key role in the induction and maintenance of cardiac arrhythmias (1,10,16,59). Cardiac tissue heterogeneities increase drastically when acute regional ischemia occurs.…”

mentioning

confidence: 99%

Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution

Sidorov¹,

Uzelac

Wikswo

2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Sidorov VY, Uzelac I, Wikswo JP. Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution. Am J Physiol Heart Circ Physiol 301: H209 -H220, 2011. First published May 2, 2011; doi:10.1152/ajpheart.01141.2010.-The heterogeneities of electrophysiological properties of cardiac tissue are the main factors that control both arrhythmia induction and maintenance. Although the local increase of extracellular potassium ([K ϩ ]o) due to coronary occlusion is a well-established metabolic response to acute ischemia, the role of local [K ϩ ]o heterogeneity in phase 1a arrhythmias has yet to be determined. In this work, we created local [K ϩ ]o heterogeneity and investigated its role in fast pacing response and arrhythmia induction. The left marginal vein of a Langendorff-perfused rabbit heart was cannulated and perfused separately with solutions containing 4, 6, 8, 10, and 12 mM of K ϩ . The fluorescence dye was utilized to map the voltage distribution. We tested stimulation rates, starting from 400 ms down to 120 ms, with steps of 5-50 ms. We found that local [K ϩ ]o heterogeneity causes action potential (AP) alternans, 2:1 conduction block, and wave breaks. The effect of [K ϩ ]o heterogeneity on electrical stability and vulnerability to arrhythmia induction was largest during regional perfusion with 10 mM of K ϩ . We detected three concurrent dynamics: normally propagating activation when excitation waves spread over tissue perfused with normal K ϩ , alternating 2:2 rhythm near the border of [K ϩ ]o heterogeneity, and 2:1 aperiodicity when propagation was within the high [K ϩ ]o area. [K ϩ ]o elevation changed the AP duration (APD) restitution and shifted the restitution curve toward longer diastolic intervals and shorter APD. We conclude that spatial heterogeneity of the APD restitution, created with regional elevation of [K ϩ ]o, can lead to AP instability, 2:1 block, and reentry induction. restitution heterogeneity; regional perfusion; optical mapping THE STATIONARY AND DYNAMIC heterogeneities of electrophysiological properties of cardiac tissue play a key role in the induction and maintenance of cardiac arrhythmias (1,10,16,59). Cardiac tissue heterogeneities increase drastically when acute regional ischemia occurs. The early stage of acute ischemia is characterized by abrupt metabolic and electrophysiological changes in the affected area (11). Among them, the more prominent are increased extracellular potassium ([K ϩ ] o ) (25, 26), decreased creatine phosphate (43, 63), elevated intracellular inorganic phosphate (63), acidosis (27, 46), catecholamine release (39), and partial depolarization of transmembrane potential (V m ) (28,36).Since an early change in V m closely relates to [K ϩ ] o accumulation (34, 60), the K ϩ imbalance is considered to be the major factor affecting excitability and is responsible for slow impulse propagation and induction of reentry (51) Although numerous studies have been devoted to investigation ...

show abstract

mentioning

confidence: 99%

Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution

Sidorov¹,

Uzelac

Wikswo

2011

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…These data suggest that electrotonic influences are important in determining the transmural repolarization sequence in rabbit ventricular myocardium and that they are sufficient to overcome intrinsic differences in the electrophysiological properties of the cells across the ventricular wall. action potential remodeling; electrophysiology TRANSMURAL DIFFERENCES in cellular electrophysiology are known to exist in mammalian ventricular myocardium (13,47). In studies of isolated ventricular myocytes, endocardial cells display an action potential duration (APD) that is consistently longer than that of epicardial cells (9,26,28,51).…”

mentioning

confidence: 99%

Effect of activation sequence on transmural patterns of repolarization and action potential duration in rabbit ventricular myocardium

Myles

Bernus

Burton

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Myles RC, Bernus O, Burton FL, Cobbe SM, Smith GL. Effect of activation sequence on transmural patterns of repolarization and action potential duration in rabbit ventricular myocardium. Am J Physiol Heart Circ Physiol 299: H1812-H1822, 2010. First published October 1, 2010; doi:10.1152/ajpheart.00518.2010.-Although transmural heterogeneity of action potential duration (APD) is established in single cells isolated from different tissue layers, the extent to which it produces transmural gradients of repolarization in electrotonically coupled ventricular myocardium remains controversial. The purpose of this study was to examine the relative contribution of intrinsic cellular gradients of APD and electrotonic influences to transmural repolarization in rabbit ventricular myocardium. Transmural optical mapping was performed in left ventricular wedge preparations from eight rabbits. Transmural patterns of activation, repolarization, and APD were recorded during endocardial and epicardial stimulation. Experimental results were compared with modeled data during variations in electrotonic coupling. A transmural gradient of APD was evident during endocardial stimulation, which reflected differences previously seen in isolated cells, with the longest APD at the endocardium and the shortest at the epicardium (endo: 165 Ϯ 5 vs. epi: 147 Ϯ 4 ms; P Ͻ 0.05). During epicardial stimulation, this gradient reversed (epi: 162 Ϯ 4 vs. endo: 148 Ϯ 6 ms; P Ͻ 0.05). In both activation sequences, transmural repolarization followed activation and APD shortened along the activation path such that significant transmural gradients of repolarization did not occur. This correlation between transmural activation time and APD was recapitulated in simulations and varied with changes in intercellular coupling, confirming that it is mediated by electrotonic current flow between cells. These data suggest that electrotonic influences are important in determining the transmural repolarization sequence in rabbit ventricular myocardium and that they are sufficient to overcome intrinsic differences in the electrophysiological properties of the cells across the ventricular wall. action potential remodeling; electrophysiology TRANSMURAL DIFFERENCES in cellular electrophysiology are known to exist in mammalian ventricular myocardium (13,47). In studies of isolated ventricular myocytes, endocardial cells display an action potential duration (APD) that is consistently longer than that of epicardial cells (9,26,28,51). Furthermore, ventricular M cells with distinct electrophysiological characteristics have been identified in the midmyocardium of some mammals, including rabbit (26), dog (40), and human (10,19). At slow stimulation rates, M cells display an APD that is much longer than cells isolated from either epi-or endocardial regions. The dominant influence of these cellular electrophysiological heterogeneities in intact myocardium has been suggested by studies using microelectrode recordings from three regions on the transmural surface of isolated canine ve...

show abstract

“…The involved mechanisms consist of myocardial fibrosis, changes in cell and tissue architecture, membrane excitability, and alterations of gap-junctional coupling (Libby et al, 2008). Gap junctions are required for electrical impulse propagation and synchronous contraction in the healthy heart and their alterations might contribute to abnormal conduction and thus be a substrate for arrhythmia (von Olshausen et al, 1983;Kligfield et al, 1987;Kostin et al, 2003;Wiegerinck et al, 2008). The main protein forming gap junctions in rat ventricular myocardium is connexin43 (Sohl and Willecke, 2004).…”

mentioning

confidence: 99%

Myocardial Morphological Characteristics and Proarrhythmic Substrate in the Rat Model of Heart Failure Due to Chronic Volume Overload

Beneš

Melenovský

Škaroupková

et al. 2010

The Anatomical Record

View full text Add to dashboard Cite

Chronic volume overload leads to cardiac hypertrophy and later to heart failure (HF), which are both associated with increased risk of cardiac arrhythmias. The goal of this study was to describe changes in myocardial morphology and to characterize arrhythmogenic substrate in rat model of developing HF due to volume overload. An arteriovenous fistula (AVF) was created in male Wistar rats between the inferior vena cava and abdominal aorta using needle technique. Myocardial morphology, tissue fibrosis, and connexin43 distribution, localization and phosphorylation were examined using confocal microscopy and Western blotting in the stage of compensated hypertrophy (11 weeks), and decompensated HF (21 weeks). Heart to body weight (BW) ratio was 89% and 133% higher in AVF rats at 11 and 21 weeks, respectively. At 21 weeks but not 11 weeks, AVF rats had pulmonary congestion (increased lung to BW ratio) indicating presence of decompensated HF. The myocytes in left ventricular midmyocardium were significantly thicker (þ8% and þ45%) and longer (þ88% and þ97%). Despite extensive hypertrophy, there was no excessive fibrosis in the AVF ventricles. Distribution and localization of connexin43 were similar between groups, but its phosphorylation was significantly lower in AVF hearts at 21st week, but not 11th week, suggesting that HF,

show abstract

Transmural dispersion of refractoriness and conduction velocity is associated with heterogeneously reduced connexin43 in a rabbit model of heart failure

Cited by 58 publications

References 35 publications

Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution

Regional increase of extracellular potassium leads to electrical instability and reentry occurrence through the spatial heterogeneity of APD restitution

Effect of activation sequence on transmural patterns of repolarization and action potential duration in rabbit ventricular myocardium

Myocardial Morphological Characteristics and Proarrhythmic Substrate in the Rat Model of Heart Failure Due to Chronic Volume Overload

Contact Info

Product

Resources

About