Arrhythmogenesis by single ectopic beats originating in the Purkinje system

Abstract

Cells in the Purkinje system (PS) are known to be more vulnerable than ventricular myocytes to secondary excitations during the action potential (AP) plateau or repolarization phases, known as early afterdepolarizations (EADs). Since myocytes have a lower intrinsic AP duration than the PS cells to which they are coupled, EADs occurring in distal branches of the PS are more likely to result in propagating ectopic beats. In this study, we use a computer model of the rabbit ventricles and PS to investigate the consequences of EADs occurring at different times and places in the cardiac conduction system. We quantify the role of tissue conductivity and excitability, as well as interaction with sinus excitation, in determining whether an EAD-induced ectopic beat will establish reentrant activity. We demonstrate how a single ectopic beat arising from an EAD in the distal PS can give rise to reentrant arrhythmia; in contrast, EADs in the proximal PS were unable to initiate reentry. Clinical studies have established the PS as a potential substrate for reentry, but the underlying mechanisms of these types of disorder are not well understood, nor are conditions leading to their development clearly defined; this work provides new insights into the role of the PS in such circumstances. Our findings indicate that simulated EADs in the distal PS can induce premature beats, which can lead to the tachycardias involving the conduction system due to interactions with sinus activity or impaired myocardial conduction velocity.

Three-Dimensional Impulse Propagation in Myocardium

“…The effects of dispersion of repolarization on initiation of reentry in the HPS were investigated recently by Deo et al 84 using an anatomically realistic 3D model of the rabbit ventricles and conduction system. APD was longer in proximal than in distal Purkinje fibers, attributable in part to peripheral electronic coupling with ventricular myocytes.…”

Miocardiocitos conducentes ventriculares

“…Cuando se dan en las fibras conducentes, crean focos ectópicos arrítmicos con lesión del miocardio ventricular, lo que puede ser común en el postinfarto de miocardio, en alteraciones del intercambio iónico de entrada o salida durante la repolarización, algunos medicamentos antiarrítmicos y la isquemia miocárdica más de 30 minutos. [30][31][32][33][34] Los procesos arritmogénicos en los que están involucradas las células miocárdicas conducentes ventriculares incluyen la insuficiencia cardiaca congestiva, el síndrome de QT prolongado y la taquicardia ventricular. [35][36][37][38] Los modelos matemáticos, experimentos con células madre y matrices para regeneración de tejidos en el campo de la ingeniería tisular, han reproducido los procesos fisiológicos de intercambio iónico y características de las corrientes de entrada y salida, para simular los mecanismos de patogénesis.…”

Cardiac Arrhythmias: Mechanistic Knowledge and Innovation from Computer Models

“…The PS plays a critical role in the coordination of ventricular excitation but it has also been implicated as a key player in arrhythmia initiation and maintenance [36,44,45,102]. Unfortunately, detailed analysis of PS contributions is difficult because its spatiotemporal excitation sequence in the intact heart must be inferred from lowamplitude electrograms [102].…”

“…Simulations that require application of the bidomain formulation (e.g., defibrillation studies [23,44,96,97,116]) are more time-consuming than those in which the monodomain formulation is adequate. Mesh size varies dramatically depending on the size of the model and the resolution necessary to capture details relevant to phenomena of interest; this review discusses studies involving models with degrees of freedom (i.e., mesh nodes) ranging from hundreds of thousands [32,33,44,45,[104][105][106][107] to millions [19,[21][22][23][96][97][98] and even tens of millions [95]. At the cell level, ionic models that aim to represent different levels of detail vary considerably in terms of the size of the associated ODE system; for example, the Courtemanche human atrial model has 19 equations [43], the O'Hara human ventricular model has 43 [91], and the Sampson human Purkinje fiber model has 83 [108].…”