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Changes in Myocardial Composition and Conduction Properties in Rat Heart Failure Model Induced by Chronic Volume Overload

Volume overload leads to development of eccentric cardiac hypertrophy and heart failure. In our previous report, we have shown myocyte hypertrophy with no fibrosis and decrease in gap junctional coupling via connexin43 in a rat model of aorto-caval fistula at 21 weeks. Here we set to analyze the ele...

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Autores principales: Sedmera, David, Neckar, Jan, Benes, Jiri, Pospisilova, Jana, Petrak, Jiri, Sedlacek, Kamil, Melenovsky, Vojtech
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997968/
https://www.ncbi.nlm.nih.gov/pubmed/27610087
http://dx.doi.org/10.3389/fphys.2016.00367
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author Sedmera, David
Neckar, Jan
Benes, Jiri
Pospisilova, Jana
Petrak, Jiri
Sedlacek, Kamil
Melenovsky, Vojtech
author_facet Sedmera, David
Neckar, Jan
Benes, Jiri
Pospisilova, Jana
Petrak, Jiri
Sedlacek, Kamil
Melenovsky, Vojtech
author_sort Sedmera, David
collection PubMed
description Volume overload leads to development of eccentric cardiac hypertrophy and heart failure. In our previous report, we have shown myocyte hypertrophy with no fibrosis and decrease in gap junctional coupling via connexin43 in a rat model of aorto-caval fistula at 21 weeks. Here we set to analyze the electrophysiological and protein expression changes in the left ventricle and correlate them with phenotypic severity based upon ventricles to body weight ratio. ECG analysis showed increased amplitude and duration of the P wave, prolongation of PR and QRS interval, ST segment elevation and decreased T wave amplitude in the fistula group. Optical mapping showed a prolongation of action potential duration in the hypertrophied hearts. Minimal conduction velocity (CV) showed a bell-shaped curve, with a significant increase in the mild cases and there was a negative correlation of both minimal and maximal CV with heart to body weight ratio. Since the CV is influenced by gap junctional coupling as well as the autonomic nervous system, we measured the amounts of tyrosine hydroxylase (TH) and choline acetyl transferase (ChAT) as a proxy for sympathetic and parasympathetic innervation, respectively. At the protein level, we confirmed a significant decrease in total and phosphorylated connexin43 that was proportional to the level of hypertrophy, and similarly decreased levels of TH and ChAT. Even at a single time-point, severity of morphological phenotype correlates with progression of molecular and electrophysiological changes, with the most hypertrophied hearts showing the most severe changes that might be related to arrhythmogenesis.
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spelling pubmed-49979682016-09-08 Changes in Myocardial Composition and Conduction Properties in Rat Heart Failure Model Induced by Chronic Volume Overload Sedmera, David Neckar, Jan Benes, Jiri Pospisilova, Jana Petrak, Jiri Sedlacek, Kamil Melenovsky, Vojtech Front Physiol Physiology Volume overload leads to development of eccentric cardiac hypertrophy and heart failure. In our previous report, we have shown myocyte hypertrophy with no fibrosis and decrease in gap junctional coupling via connexin43 in a rat model of aorto-caval fistula at 21 weeks. Here we set to analyze the electrophysiological and protein expression changes in the left ventricle and correlate them with phenotypic severity based upon ventricles to body weight ratio. ECG analysis showed increased amplitude and duration of the P wave, prolongation of PR and QRS interval, ST segment elevation and decreased T wave amplitude in the fistula group. Optical mapping showed a prolongation of action potential duration in the hypertrophied hearts. Minimal conduction velocity (CV) showed a bell-shaped curve, with a significant increase in the mild cases and there was a negative correlation of both minimal and maximal CV with heart to body weight ratio. Since the CV is influenced by gap junctional coupling as well as the autonomic nervous system, we measured the amounts of tyrosine hydroxylase (TH) and choline acetyl transferase (ChAT) as a proxy for sympathetic and parasympathetic innervation, respectively. At the protein level, we confirmed a significant decrease in total and phosphorylated connexin43 that was proportional to the level of hypertrophy, and similarly decreased levels of TH and ChAT. Even at a single time-point, severity of morphological phenotype correlates with progression of molecular and electrophysiological changes, with the most hypertrophied hearts showing the most severe changes that might be related to arrhythmogenesis. Frontiers Media S.A. 2016-08-25 /pmc/articles/PMC4997968/ /pubmed/27610087 http://dx.doi.org/10.3389/fphys.2016.00367 Text en Copyright © 2016 Sedmera, Neckar, Benes, Pospisilova, Petrak, Sedlacek and Melenovsky. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Sedmera, David
Neckar, Jan
Benes, Jiri
Pospisilova, Jana
Petrak, Jiri
Sedlacek, Kamil
Melenovsky, Vojtech
Changes in Myocardial Composition and Conduction Properties in Rat Heart Failure Model Induced by Chronic Volume Overload
title Changes in Myocardial Composition and Conduction Properties in Rat Heart Failure Model Induced by Chronic Volume Overload
title_full Changes in Myocardial Composition and Conduction Properties in Rat Heart Failure Model Induced by Chronic Volume Overload
title_fullStr Changes in Myocardial Composition and Conduction Properties in Rat Heart Failure Model Induced by Chronic Volume Overload
title_full_unstemmed Changes in Myocardial Composition and Conduction Properties in Rat Heart Failure Model Induced by Chronic Volume Overload
title_short Changes in Myocardial Composition and Conduction Properties in Rat Heart Failure Model Induced by Chronic Volume Overload
title_sort changes in myocardial composition and conduction properties in rat heart failure model induced by chronic volume overload
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997968/
https://www.ncbi.nlm.nih.gov/pubmed/27610087
http://dx.doi.org/10.3389/fphys.2016.00367
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