Comparison of Detailed and Simplified Models of Human Atrial Myocytes to Recapitulate Patient Specific Properties.

Computer studies are often used to study mechanisms of cardiac arrhythmias, including atrial fibrillation (AF). A crucial component in these studies is the electrophysiological model that describes the membrane potential of myocytes. The models vary from detailed, describing numerous ion channels, t...

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Main Authors: Daniel M Lombardo, Flavio H Fenton, Sanjiv M Narayan, Wouter-Jan Rappel
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-08-01
Series:PLoS Computational Biology
Online Access:http://europepmc.org/articles/PMC4975409?pdf=render
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author Daniel M Lombardo
Flavio H Fenton
Sanjiv M Narayan
Wouter-Jan Rappel
author_facet Daniel M Lombardo
Flavio H Fenton
Sanjiv M Narayan
Wouter-Jan Rappel
author_sort Daniel M Lombardo
collection DOAJ
description Computer studies are often used to study mechanisms of cardiac arrhythmias, including atrial fibrillation (AF). A crucial component in these studies is the electrophysiological model that describes the membrane potential of myocytes. The models vary from detailed, describing numerous ion channels, to simplified, grouping ionic channels into a minimal set of variables. The parameters of these models, however, are determined across different experiments in varied species. Furthermore, a single set of parameters may not describe variations across patients, and models have rarely been shown to recapitulate critical features of AF in a given patient. In this study we develop physiologically accurate computational human atrial models by fitting parameters of a detailed and of a simplified model to clinical data for five patients undergoing ablation therapy. Parameters were simultaneously fitted to action potential (AP) morphology, action potential duration (APD) restitution and conduction velocity (CV) restitution curves in these patients. For both models, our fitting procedure generated parameter sets that accurately reproduced clinical data, but differed markedly from published sets and between patients, emphasizing the need for patient-specific adjustment. Both models produced two-dimensional spiral wave dynamics for that were similar for each patient. These results show that simplified, computationally efficient models are an attractive choice for simulations of human atrial electrophysiology in spatially extended domains. This study motivates the development and validation of patient-specific model-based mechanistic studies to target therapy.
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spelling doaj.art-2f2cd220d8664646ae99d10bcc6a5c2a2022-12-22T03:41:43ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582016-08-01128e100506010.1371/journal.pcbi.1005060Comparison of Detailed and Simplified Models of Human Atrial Myocytes to Recapitulate Patient Specific Properties.Daniel M LombardoFlavio H FentonSanjiv M NarayanWouter-Jan RappelComputer studies are often used to study mechanisms of cardiac arrhythmias, including atrial fibrillation (AF). A crucial component in these studies is the electrophysiological model that describes the membrane potential of myocytes. The models vary from detailed, describing numerous ion channels, to simplified, grouping ionic channels into a minimal set of variables. The parameters of these models, however, are determined across different experiments in varied species. Furthermore, a single set of parameters may not describe variations across patients, and models have rarely been shown to recapitulate critical features of AF in a given patient. In this study we develop physiologically accurate computational human atrial models by fitting parameters of a detailed and of a simplified model to clinical data for five patients undergoing ablation therapy. Parameters were simultaneously fitted to action potential (AP) morphology, action potential duration (APD) restitution and conduction velocity (CV) restitution curves in these patients. For both models, our fitting procedure generated parameter sets that accurately reproduced clinical data, but differed markedly from published sets and between patients, emphasizing the need for patient-specific adjustment. Both models produced two-dimensional spiral wave dynamics for that were similar for each patient. These results show that simplified, computationally efficient models are an attractive choice for simulations of human atrial electrophysiology in spatially extended domains. This study motivates the development and validation of patient-specific model-based mechanistic studies to target therapy.http://europepmc.org/articles/PMC4975409?pdf=render
spellingShingle Daniel M Lombardo
Flavio H Fenton
Sanjiv M Narayan
Wouter-Jan Rappel
Comparison of Detailed and Simplified Models of Human Atrial Myocytes to Recapitulate Patient Specific Properties.
PLoS Computational Biology
title Comparison of Detailed and Simplified Models of Human Atrial Myocytes to Recapitulate Patient Specific Properties.
title_full Comparison of Detailed and Simplified Models of Human Atrial Myocytes to Recapitulate Patient Specific Properties.
title_fullStr Comparison of Detailed and Simplified Models of Human Atrial Myocytes to Recapitulate Patient Specific Properties.
title_full_unstemmed Comparison of Detailed and Simplified Models of Human Atrial Myocytes to Recapitulate Patient Specific Properties.
title_short Comparison of Detailed and Simplified Models of Human Atrial Myocytes to Recapitulate Patient Specific Properties.
title_sort comparison of detailed and simplified models of human atrial myocytes to recapitulate patient specific properties
url http://europepmc.org/articles/PMC4975409?pdf=render
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