Human atrial cell models to analyse haemodialysis-related effects on cardiac electrophysiology: work in progress.

Elisa Passini,Simonetta Genovesi,Stefano Severi

doi:10.1155/2014/291598

Elisa Passini, Simonetta Genovesi + Show 1 more

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https://doi.org/10.1155/2014/291598

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Abstract

During haemodialysis (HD) sessions, patients undergo alterations in the extracellular environment, mostly concerning plasma electrolyte concentrations, pH, and volume, together with a modification of sympathovagal balance. All these changes affect cardiac electrophysiology, possibly leading to an increased arrhythmic risk. Computational modeling may help to investigate the impact of HD-related changes on atrial electrophysiology. However, many different human atrial action potential (AP) models are currently available, all validated only with the standard electrolyte concentrations used in experiments. Therefore, they may respond in different ways to the same environmental changes. After an overview on how the computational approach has been used in the past to investigate the effect of HD therapy on cardiac electrophysiology, the aim of this work has been to assess the current state of the art in human atrial AP models, with respect to the HD context. All the published human atrial AP models have been considered and tested for electrolytes, volume changes, and different acetylcholine concentrations. Most of them proved to be reliable for single modifications, but all of them showed some drawbacks. Therefore, there is room for a new human atrial AP model, hopefully able to physiologically reproduce all the HD-related effects. At the moment, work is still in progress in this specific field.

Highlights

In the last fifteen years, the increasing interest towards atrial electrophysiology and atrial fibrillation (AF), together with a greater availability of experimental data, led to remarkable developments in human atrial action potential (AP) models [1,2,3,4,5,6]
After an overview on how the computational approach has been used in the past to investigate the effect of HD therapy on cardiac electrophysiology, the aim of this work has been to assess the current state of the art in human atrial AP models, with respect to the HD context
The upper [K+]o value (9 mM) is a bit high compared to the pre-HD measurements available (e.g., 4.9 ± 0.5 mM in [30], 5.3 ± 0.9 mM in [56]) but we extended the range on purpose, since there are clinical contexts, such as acute ischemia, in which [K+]Tohceamn aloincaelflfyecritsoefuapdteoc9remasMe inor[Km+o]roes[h5o7u].ld be a hyperpolarization of the cell membrane, due to a different Nernst potential for K+ ions

Summary

Introduction

In the last fifteen years, the increasing interest towards atrial electrophysiology and atrial fibrillation (AF), together with a greater availability of experimental data, led to remarkable developments in human atrial action potential (AP) models [1,2,3,4,5,6]. Haemodialysis (HD) therapy represents a unique model to test in vivo, in human, the effects of sudden changes in plasma ionic concentrations and blood volume: in a few hours, patients undergo significant plasma electrolytes variations, together with a significant decrease in extracellular volume. The HD session causes removal of excess Na+ and water, the extent of which depends on the interdialytic weight gain of the patient. Plasmatic K+ concentration increases during the interdialytic interval, so that during all HD sessions its level must decrease, while Ca2+ variations might change depending on the dialysate Ca2+ concentration and its relationship with pre-HD plasma Ca2+ levels. The incidence of AF in end-stage renal disease patients is high: reported rates vary between 7% and 27% [18, 19], and HD session may promote AF onset [20, 21]

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