Transmural repolarisation in the left ventricle in humans during normoxia and ischaemia

Taggart, Peter; Sutton, Peter; Opthof, Tobias; Coronel, Ruben; Trimlett, Richard; Pugsley, W; Kallis, P

doi:10.1016/s0008-6363(01)00223-1

Cited by 148 publications

(100 citation statements)

References 36 publications

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“…The results of our simulation suggest that the physiological morphologies of T waves are generated mainly by the transmural distribution of APD, although the contribution of the apicobasal gradient is also important. Although recent studies suggest that the cancellation effect in the intact heart can minimize transmural dispersion (5,41,42), a large apicobasal gradient is required to observe positive T waves in limb and left precordial leads under such conditions (Fig. 4C).…”

Section: Discussionmentioning

confidence: 97%

“…During surgery or in animal experiments, subjects receive anesthetic agents that may block sodium and/or delayed rectifier potassium currents, causing preferential shortening of the APD of M cells (31). Furthermore, the plunge electrode technique used in many studies may not necessarily probe the whole area and depth of the ventricular wall (42,48). In a recent study, optical mapping revealed the distribution of APD in human ventricular tissue (12); however, only the posterior wall wedge was examined.…”

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confidence: 99%

“…For instance, measurement of the human ventricles during cardiac surgery, rather than isolated cells or a ventricular wedge, produced no significant transmural heterogeneity of repolarization (42). The electronic cancellation effect introduced by intercellular coupling through gap junctions is considered the cause of these observations in intact preparations (5,41), although experimental artifact has also been suggested (1).…”

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confidence: 99%

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Transmural and apicobasal gradients in repolarization contribute to T-wave genesis in human surface ECG

Okada

Washio

Maehara

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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The cellular basis of the T-wave morphology of surface ECG remains controversial in clinical cardiology. We examined the effect of action potential duration (APD) distribution on T-wave morphology using a realistic model of the human ventricle and torso. We developed a finite-element model of the ventricle consisting of ϳ26 million elements, including the conduction system, each implemented with the ion current model of cardiomyocytes. This model was embedded in a torso model with distinct organ structures to obtain the standard ECG leads. The APD distribution was changed in the transmural direction by locating the M cells in either the endocardial or epicardial region. We also introduced apicobasal gradients by modifying the ion channel parameters. Both the transmural gradient (with M cells on the endocardial side) and the apicobasal gradient produced positive T waves, although a very large gradient was required for the apicobasal gradient. By contrast, T waves obtained with the transmural gradient were highly symmetric and, therefore, did not represent the true physiological state. Only combination of the transmural and the moderate apicobasal gradients produced physiological T waves in surface ECG. Positive T waves in surface ECG mainly originated from the transmural distribution of APD with M cells on the endocardial side, although the apicobasal gradient was also required to attain the physiological waveform.electrocardiogram; computer simulation; T wave; body surface map; M cells DESPITE ITS LONG HISTORY AND worldwide use in clinical cardiology for the diagnosis of various heart diseases, the cellular origin of the ECG waveform is not fully established. In particular, the genesis of the T wave remains controversial, largely because of its implication in arrhythmogenesis (1,4,20,22). The T wave was originally considered to result from the heterogeneity of repolarization of the ventricle in the apicobasal direction (19). However, more recently, the transmural difference (gradient) of repolarization is considered important, as supported by the discovery of M cells isolated from the canine ventricular wall (2, 32). M cells are distributed in the deep subendocardium in the anterior wall, but are shifted to the deep subepicardium in the posterior wall, and are characterized by a longer action potential duration (APD) compared with the epicardial and endocardial myocytes, creating a significant gradient (1). Subsequent studies identified similar type of cells in guinea pig, rabbit, pig, and human ventricular tissues (8,33,35,51).However, when measurements are made in more intact preparations, there is accumulating evidence that the APD of M cells becomes shorter, resulting in smaller transmural dispersion (23). For instance, measurement of the human ventricles during cardiac surgery, rather than isolated cells or a ventricular wedge, produced no significant transmural heterogeneity of repolarization (42). The electronic cancellation effect introduced by intercellular coupling through gap junctions is considered t...

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Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Transmural and apicobasal gradients in repolarization contribute to T-wave genesis in human surface ECG

Okada

Washio

Maehara

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…The resultant transmural repolarization gradients dictated the characteristics of the voltage signal recorded across the isolated ventricular wall, analogous to the ECG T wave. In contrast, a number of studies (15,42,19) in human hearts have suggested that under physiological conditions, electrotonic influences abolish transmural electrical gradients during repolarization. These data question the importance of transmural gradients of repolarization in the ECG T wave, the origin of which remains controversial after decades of investigation (30,32).…”

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confidence: 94%

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

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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...

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“…3, panel IV, as well as in previous studies (Yan et al, 1998b;Gima and Rudy, 2002;Idriss and Wolf, 2004;Ritsema van Eck et al, 2005). It should be noted however, that, while there is a large body of evidence supporting the existence of transmural heterogeneities in ionic currents and electrophysiological properties of ventricular tissue, some experimental studies have documented little or no transmural differences in APD in vivo (Anyukhovsky et al, 1996(Anyukhovsky et al, ,1999Taggart et al, 2001;Conrath et al;.…”

Section: Transmural Electrophysiological Heterogeneities In the Ventrmentioning

confidence: 56%

The role of transmural ventricular heterogeneities in cardiac vulnerability to electric shocks

Maharaj

Blake

Trayanova

et al. 2008

Progress in Biophysics and Molecular Biology

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Transmural electrophysiological heterogeneities have been shown to contribute to arrhythmia induction in the heart; however, their role in defibrillation failure has never been examined. The goal of this study is to investigate how transmural heterogeneities in ionic currents and gap-junctional coupling contribute to arrhythmia generation following defibrillation strength shocks. This study used a 3D anatomically realistic bidomain model of the rabbit ventricles. Transmural heterogeneity in ionic currents and reduced sub-epicardial intercellular coupling were incorporated based on experimental data. The ventricles were paced apically, and truncated-exponential monophasic shocks of varying strength and timing were applied via large external electrodes. Simulations demonstrate that inclusion of transmural heterogeneity in ionic currents results in an increase in vulnerability to shocks, reflected in the increased upper limit of vulnerability, ULV, and the enlarged vulnerable window, VW. These changes in vulnerability stem from increased post-shock dispersion in repolarisation as it increases the likelihood of establishment of re-entrant circuits. In contrast, reduced sub-epicardial coupling results in decrease in both ULV and VW. This decrease is caused by altered virtual electrode polarisation around the region of sub-epicardal uncoupling, and specifically, by the increase in (1) the amount of positively polarised myocardium at shock-end and (2) the spatial extent of post-shock wavefronts.

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Transmural repolarisation in the left ventricle in humans during normoxia and ischaemia

Cited by 148 publications

References 36 publications

Transmural and apicobasal gradients in repolarization contribute to T-wave genesis in human surface ECG

Transmural and apicobasal gradients in repolarization contribute to T-wave genesis in human surface ECG

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

The role of transmural ventricular heterogeneities in cardiac vulnerability to electric shocks

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