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The effect of the sphingosine‐1‐phosphate analogue FTY720 on atrioventricular nodal tissue

The sphingosine‐1‐phosphate (S1P) receptor modulator, fingolimod (FTY720), has been used for the treatment of patients with relapsing forms of multiple sclerosis, but atrioventricular (AV) conduction block have been reported in some patients after the first dose. The underlying mechanism of this AV...

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Autores principales: Egom, Emmanuel E., Kruzliak, Peter, Rotrekl, Vladimir, Lei, Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511369/
https://www.ncbi.nlm.nih.gov/pubmed/25864579
http://dx.doi.org/10.1111/jcmm.12549
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author Egom, Emmanuel E.
Kruzliak, Peter
Rotrekl, Vladimir
Lei, Ming
author_facet Egom, Emmanuel E.
Kruzliak, Peter
Rotrekl, Vladimir
Lei, Ming
author_sort Egom, Emmanuel E.
collection PubMed
description The sphingosine‐1‐phosphate (S1P) receptor modulator, fingolimod (FTY720), has been used for the treatment of patients with relapsing forms of multiple sclerosis, but atrioventricular (AV) conduction block have been reported in some patients after the first dose. The underlying mechanism of this AV node conduction blockade is still not well‐understood. In this study, we hypothesize that expression of this particular arrhythmia might be related to a direct effect of FTY720 on AV node rather than a parasympathetic mimetic action. We, therefore, investigated the effect of FTY720 on AV nodal, using in vitro rat model preparation, under both basal as well as ischaemia/reperfusion conditions. We first look at the expression pattern of S1P receptors on the AV node using real‐time PCR. Although all three S1P receptor isoforms were expressed in AVN tissues, S1P1 receptor isoform expression level was higher than S1P2 and S1P3. The effect of 25 nM FTY720 on cycle length (CL) was subsequently studied via extracellular potentials recordings. FTY720 caused a mild to moderate prolongation in CL by an average 9% in AVN (n = 10, P < 0.05) preparations. We also show that FTY720 attenuated both ischaemia and reperfusion induced AVN rhythmic disturbance. To our knowledge, these remarkable findings have not been previously reported in the literature, and stress the importance for extensive monitoring period in certain cases, especially in patients taking concurrently AV node blocker agents.
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spelling pubmed-45113692015-07-28 The effect of the sphingosine‐1‐phosphate analogue FTY720 on atrioventricular nodal tissue Egom, Emmanuel E. Kruzliak, Peter Rotrekl, Vladimir Lei, Ming J Cell Mol Med Original Articles The sphingosine‐1‐phosphate (S1P) receptor modulator, fingolimod (FTY720), has been used for the treatment of patients with relapsing forms of multiple sclerosis, but atrioventricular (AV) conduction block have been reported in some patients after the first dose. The underlying mechanism of this AV node conduction blockade is still not well‐understood. In this study, we hypothesize that expression of this particular arrhythmia might be related to a direct effect of FTY720 on AV node rather than a parasympathetic mimetic action. We, therefore, investigated the effect of FTY720 on AV nodal, using in vitro rat model preparation, under both basal as well as ischaemia/reperfusion conditions. We first look at the expression pattern of S1P receptors on the AV node using real‐time PCR. Although all three S1P receptor isoforms were expressed in AVN tissues, S1P1 receptor isoform expression level was higher than S1P2 and S1P3. The effect of 25 nM FTY720 on cycle length (CL) was subsequently studied via extracellular potentials recordings. FTY720 caused a mild to moderate prolongation in CL by an average 9% in AVN (n = 10, P < 0.05) preparations. We also show that FTY720 attenuated both ischaemia and reperfusion induced AVN rhythmic disturbance. To our knowledge, these remarkable findings have not been previously reported in the literature, and stress the importance for extensive monitoring period in certain cases, especially in patients taking concurrently AV node blocker agents. John Wiley and Sons Inc. 2015-07 2015-04-13 /pmc/articles/PMC4511369/ /pubmed/25864579 http://dx.doi.org/10.1111/jcmm.12549 Text en © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Egom, Emmanuel E.
Kruzliak, Peter
Rotrekl, Vladimir
Lei, Ming
The effect of the sphingosine‐1‐phosphate analogue FTY720 on atrioventricular nodal tissue
title The effect of the sphingosine‐1‐phosphate analogue FTY720 on atrioventricular nodal tissue
title_full The effect of the sphingosine‐1‐phosphate analogue FTY720 on atrioventricular nodal tissue
title_fullStr The effect of the sphingosine‐1‐phosphate analogue FTY720 on atrioventricular nodal tissue
title_full_unstemmed The effect of the sphingosine‐1‐phosphate analogue FTY720 on atrioventricular nodal tissue
title_short The effect of the sphingosine‐1‐phosphate analogue FTY720 on atrioventricular nodal tissue
title_sort effect of the sphingosine‐1‐phosphate analogue fty720 on atrioventricular nodal tissue
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511369/
https://www.ncbi.nlm.nih.gov/pubmed/25864579
http://dx.doi.org/10.1111/jcmm.12549
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