Subepicardial Action Potential Characteristics Are a Function of Depth and Activation Sequence in Isolated Rabbit Hearts

Abstract

V entricular electric propagation is governed by activation sequence, electric properties of the myocardial syncytium, and anatomy of the ventricular wall.1,2 Time course and rate of propagation of the action potential (AP) depends on ionic current flow across sarcolemmal membranes and the electric resistance and capacitance of nearby myocardium. 3 These factors are heterogeneous across the ventricular wall; because of polarized gap junction distribution, intercellular resistance depends on myocardial fiber orientation 4 ; electrotonic load at any given point in the myocardium depends on the activation sequence and distance from structural features, such as the epicardial surface. In addition, ion channel expression is heterogeneous in the apex-base 5 and endocardial-epicardial axes. 6 Therefore, the rate of depolarization of the AP reflects myocardial excitability. However, the influence of activation sequence on AP upstroke is still a matter of debate. 7,8 Although continuous cable theory predicts that a higher conduction velocity (CV) is associated with higher maximal upstroke velocity (dV/dt max ), 9 on the surface of isolated cardiac muscle preparations longitudinal propagation results in faster CV but lower dV/dt max relative to transverse propagation. 10 These observations were explained by (1) predominantly axial connexin distribution and (2) arrangement of capillary vessels parallel to the longitudinal axis of the cells.11 This has been challenged by computational modeling, which suggests that differences in upstroke characteristics are limited to myocardium close to the epicardial surface.7 Until now, this could not be verified experimentally because of the technical difficulty associated with accurate transmembrane © 2013 American Heart Association, Inc. Original Article Circ Arrhythm ElectrophysiolBackground-Electric excitability in the ventricular wall is influenced by cellular electrophysiology and passive electric properties of the myocardium. Action potential (AP) rise time, an indicator of myocardial excitability, is influenced by conduction pattern and distance from the epicardial surface. This study examined AP rise times and conduction velocity as the depolarizing wavefront approaches the epicardial surface. Methods and Results-Two-photon excitation of di-4-aminonaphthenyl-pyridinum-propylsulfonate was used to measure electric activity at discrete epicardial layers of isolated Langendorff-perfused rabbit hearts to a depth of 500 μm. Endoto-epicardial wavefronts were studied during right atrial or ventricular endocardial pacing. Similar measurements were made with epi-to-endocardial, transverse, and longitudinal pacing protocols. Results were compared with data from a bidomain model of 3-dimensional (3D) electric propagation within ventricular myocardium. During right atrial and endocardial pacing, AP rise time (10%-90% of upstroke) decreased by ≈50% between 500 and 50 μm from the epicardial surface, whereas conduction velocity increased and AP duration was only slightly shorter (≈4%). The...

β-Adrenergic modulation of myocardial conduction velocity: Connexins vs. sodium current

“…Recently this relationship was examined in using AP measurements in all 3 dimensions of the myocardium. The study concluded that dV/dtmax was unaffected by propagation direction deep within the myocardium and that AP rise time was a dictated by a balance between INa and the downstream axial current developed by the myocardium [56].…”

Bidomain Predictions of Virtual Electrode-Induced Make and Break Excitations around Blood Vessels

“…This is just enough current to excite longitudinally but not transversely, with a partial activation of the fast sodium channel (Boyle et al, 2012). The electrotonic loading is also lower near the boundary due to the boundary condition, so a lower transmembrane current density is required to excite tissue down the concentration gradient (Kelly et al, 2013; Bishop et al, 2014). In addition, the high extracellular conductivity adjacent to the boundary (in the bath space) significantly increases the conduction velocity of the wave close to the surface (Henriquez et al, 1996, 2007; Bishop and Plank, 2011; Bishop et al, 2011).…”

Simulating photon scattering effects in structurally detailed ventricular models using a Monte Carlo approach

“…Firstly, it will provide an essential tool to facilitate a closer, and essential, validation of the predictions made from computational simulation results using these latest highly-detailed MR-based models with optical mapping recordings which, until now, has not been possible. Secondly, it will provide important insight into the underlying mechanisms of fluorescent signal distortion and the role of fine-scale structures, which may be of significant importance in facilitating a better interpretation of optical mapping signals from high-resolution imaging systems (Bub et al, 2010; Kelly et al, 2013). …”

“…Many optical mapping studies in recent years have used careful measurements of both upstroke durations and morphologies from the epicardial surface to infer detailed information regarding localized subsurface wavefront direction (Hyatt et al, 2003, 2005) and relative electrotonic loading (Kelly et al, 2013). Although, in this study we highlighted the significantly different effects on the upstroke due to the interaction of the wavefront with large sub-epicardial cavities for different overall global wavefront propagation directions (toward and parallel to the recording surface), the interaction with localized subsurface wavefront orientations with cavities may also represent an important consideration.…”