Is there a significant transmural gradient in repolarization time in the intact heart?

Opthof, Tobias; Coronel, Ruben; Janse, Michiel J.

doi:10.1161/circep.108.825356

Cited by 108 publications

(97 citation statements)

References 54 publications

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“…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).…”

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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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confidence: 99%

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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“…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). Understanding the balance between intrinsic repolarization characteristics and electrotonic influences in ventricular myocardium is therefore central to our understanding of cardiac electrophysiology.…”

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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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“…Tp-e/ QT ratio and Tp-e/QTc are calculated with electrocardiography (ECG). Tp-e/QT and Tp-e/QTc are novel indexes of ventricular arrhythmogenesis and are related to a high risk of sudden cardiac death (9)(10)(11). The Tp-e/QT ratio has been demonstrated to be a more reliable marker of ventricular arrhythmias compared to the QT interval, QTc, or Tp-e by recent studies.…”

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confidence: 99%

Tp-e/QT and Tp-e/QTc Ratio in Hemodialysis and Peritoneal Dialysis Patients

Güçlü¹,

Sipahioğlu²,

Icli³

et al. 2016

Turk Neph Dial Transpl

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OBJECTIVE: Sudden cardiac death and risk of arrhythmia are higher in patients with ESRD. Tp-e/ QT, and Tp-e/QTc are novel and more reliable indexes of ventricular arrhythmogenesis and sudden cardiac death than QTc. The aim of this study was to assess ventricular repolarization in patients with hemodialysis and peritoneal dialysis by using the Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio. MATERIAL and METHODS:A total of 35 healthy controls, 92 hemodialysis patients, and 104 peritoneal dialysis patients were enrolled in the study. The Tp-e interval, Tp-e/QT, and Tp-e/QTc ratio were calculated from the ECGs of the individuals and compared among groups. RESULTS:QT value was significantly higher in hemodialysis group compared with peritoneal dialysis group (p<0.001) and control group (p<0.001). However a difference was not found comparing QT values between peritoneal dialysis and control groups. Tp-e, Tp-e/QTc, Tp-e/QT, and QTc values were significantly higher in hemodialysis and peritoneal dialysis group comparing to control group. However a statistically significant difference was not found while comparing QTc values between peritoneal dialysis and control groups (p:0.081). When all patients of ESRD without DM were compared with the control group, Tp-e, Tp-e/QTc, Tp-e/QT, and QTc values were found significantly higher than the healthy control group. The values of Tp-e/QT (p<0.001 r:0.314) and Tp-e/QTc (p:0.018 r:0,187) in all patients with kidney disease were found to show positive correlation with duration of dialysis (month). CONCLUSION:This is the first known study that shows Tp-e/Q, and Tp-e/QTc are higher in hemodialysis and peritoneal dialysis patients. KEy wORDS:Tp-e/QT, Tp-e/QTc, Tp-e, QTc, Dialysis Öz AMAÇ: Ani kardiyak ölüm ve aritmi riski son dönem böbrek yetmezliği hastalarında yüksektir. Tp-e/ QT, ve Tp-e/QTc' nin ventriküler aritmogenezisi ve ani kardiyak ölümü göstermede QTc' den daha değerli olduğu gösterilmiştir. Çalışmada amacımız hemodiyaliz ve periton diyalizi hastalarında Tp-e intervali, Tp-e/QT ve Tp-e/QTc oranını kullanarak ventriküler repolarizasyonu değerlendirmektir. GEREÇ ve yÖNTEMLER:35 sağlıklı kontrol, 92 hemodiyaliz hastası, ve 104 periton diyalizi hastası çalışmaya dahil edildi. Bütün hastaların elektrokardiyografileri çekildi. Tp-e interval, Tp-e/QT ve Tp-e/ QTc oranı elektrokardiyografiden elde edilen verilerle hesaplandı ve gruplar arasında karşılaştırıldı. BULGULAR:QT hemodiyaliz hastalarında periton diyalizi hastalarına (p<0,001) ve sağlıklı kontrollere (p<0,001) göre yüksek saptandı. Ancak QT periton diyalizi hastalarında sağlıklı kontrollere göre anlamlı fark saptanmadı. QTc, Tp-e, Tp-e/QT, ve Tp-e/QTc hemodiyaliz ve periton diyalizi hastalarında sağlıklı kontrollere göre anlamlı yüksek tespit edildi. Bununla birlikte periton diyalizi ve kontrol grupları arasında QTc değerleri arasında farklılık tespit edilmedi (p:0,081). Diyabetik olmayan bütün son dönem böbrek yetmezliği hastaları sağlıklı kontrollerle karşılaştırıldığında QTc, Tp-e, Tp-e/ QT, ve Tp-e/QTc sağlıkl...

show abstract

Is there a significant transmural gradient in repolarization time in the intact heart?

Cited by 108 publications

References 54 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

Tp-e/QT and Tp-e/QTc Ratio in Hemodialysis and Peritoneal Dialysis Patients

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