Abstract
Recruitment of stretch-activated channels, one of the mechanisms of mechano-electric feedback, has been shown to influence the stability of scroll waves, the waves that underlie reentrant arrhythmias. However, a comprehensive study to examine the effects of recruitment of stretch-activated channels with different reversal potentials and conductances on scroll wave stability has not been undertaken; the mechanisms by which stretch-activated channel opening alters scroll wave stability are also not well understood. The goals of this study were to test the hypothesis that recruitment of stretch-activated channels affects scroll wave stability differently depending on stretch-activated channel reversal potential and channel conductance, and to uncover the relevant mechanisms underlying the observed behaviors. We developed a strongly-coupled model of human ventricular electromechanics that incorporated human ventricular geometry and fiber and sheet orientation reconstructed from MR and diffusion tensor MR images. Since a wide variety of reversal potentials and channel conductances have been reported for stretch-activated channels, two reversal potentials, −60 mV and −10 mV, and a range of channel conductances (0 to 0.07 mS/µF) were implemented. Opening of stretch-activated channels with a reversal potential of −60 mV diminished scroll wave breakup for all values of conductances by flattening heterogeneously the action potential duration restitution curve. Opening of stretch-activated channels with a reversal potential of −10 mV inhibited partially scroll wave breakup at low conductance values (from 0.02 to 0.04 mS/µF) by flattening heterogeneously the conduction velocity restitution relation. For large conductance values (>0.05 mS/µF), recruitment of stretch-activated channels with a reversal potential of −10 mV did not reduce the likelihood of scroll wave breakup because Na channel inactivation in regions of large stretch led to conduction block, which counteracted the increased scroll wave stability due to an overall flatter conduction velocity restitution.
Highlights
Experimental and clinical research has demonstrated that the mechanical environment of the heart, in health and disease, is capable of exerting influence on cardiac electrophysiology [1]
This study investigated the effects of Stretch-activated channels (SAC) opening on scroll wave stability in the fibrillating ventricles by employing a stronglycoupled MRI-based anatomically accurate 3D model of human ventricular electromechanics
A comprehensive analysis of how recruitment of SAC influences scroll wave breakup was performed for different SAC reversal potentials and channel conductances
Summary
Experimental and clinical research has demonstrated that the mechanical environment of the heart, in health and disease, is capable of exerting influence on cardiac electrophysiology [1]. The mechanisms that contribute to strain-dependent modulation of electrical wave propagation are termed mechano-electric feedback (MEF) mechanisms [2]. There are several MEF mechanisms in the heart, including stretch-induced changes in intracellular Ca handling [3], depolarization of cardiac fibroblasts by stretch (via mechano-sensitive ion channels) affecting the resting potential and action potential duration (APD) of the coupled myocyte [4], and most importantly, myocyte sarcolemmal channel activation by mechanical stimuli [5,6]. Stretch-activated channels (SAC), a type of mechanically activated ionic channels identified in cardiac tissue, have been found responsible for the generation of arrhythmias following an appropriately timed mechanical impact to the heart (commotio cordis) [7,8], as well for the termination of ventricular arrhythmias following a precordial thump [9]. Abnormal deformation associated with the establishment of arrhythmia can affect the progression of the arrhythmia itself; this aspect of MEF has received less attention in the literature
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
