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The myosin activator omecamtiv mecarbil improves wall stress in a rat model of chronic aortic regurgitation

In patients with chronic aortic regurgitation (AR), excessive preload and afterload increase left ventricle wall stress, leading to left ventricular systolic dysfunction. Thus, the objective of the present study was to evaluate the effects of the myosin activator omecamtiv mecarbil (OM) on left vent...

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Autores principales: El Oumeiri, Bachar, van de Borne, Philippe, Hubesch, Géraldine, Herpain, Antoine, Annoni, Filippo, Jespers, Pascale, Stefanidis, Constantin, Mc Entee, Kathleen, Vanden Eynden, Frédéric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371349/
https://www.ncbi.nlm.nih.gov/pubmed/34405966
http://dx.doi.org/10.14814/phy2.14988
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author El Oumeiri, Bachar
van de Borne, Philippe
Hubesch, Géraldine
Herpain, Antoine
Annoni, Filippo
Jespers, Pascale
Stefanidis, Constantin
Mc Entee, Kathleen
Vanden Eynden, Frédéric
author_facet El Oumeiri, Bachar
van de Borne, Philippe
Hubesch, Géraldine
Herpain, Antoine
Annoni, Filippo
Jespers, Pascale
Stefanidis, Constantin
Mc Entee, Kathleen
Vanden Eynden, Frédéric
author_sort El Oumeiri, Bachar
collection PubMed
description In patients with chronic aortic regurgitation (AR), excessive preload and afterload increase left ventricle wall stress, leading to left ventricular systolic dysfunction. Thus, the objective of the present study was to evaluate the effects of the myosin activator omecamtiv mecarbil (OM) on left ventricle wall stress in an experimental rat model of severe chronic AR. Forty adult male Wistar rats were randomized into two experimental groups: induction of AR (acute phase) by retrograde puncture (n = 34) or a sham intervention (n = 6). Rats that survived the acute phase (n = 18) were randomized into an OM group (n = 8) or a placebo group (n = 10). Equal volumes of OM (1.2 mg/kg/h) or placebo (0.9% NaCl) were continuously infused into the femoral vein over 30 min. OM significantly decreased end‐systolic and end‐diastolic and maximum wall stress in this experimental rat model of chronic severe AR (p < 0.001) and increased systolic performance assessed by fractional shortening and left ventricle end‐systolic diameter; both p < 0.05). These effects were correlated with decreased indices of global cardiac function (cardiac output and stroke volume; p < 0.05) but were not inferior to baseline pump indices. Infusion with placebo did not affect global cardiac function but decreased end‐systolic wall stress (p < 0.05) and increased systolic performance (all p < 0.001). In the sham‐operated (control) group, OM decreased diastolic wall stress (p < 0.05). Based on these results, OM had a favorable effect on left ventricle wall stress in an experimental rat model of severe chronic AR.
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spelling pubmed-83713492021-08-23 The myosin activator omecamtiv mecarbil improves wall stress in a rat model of chronic aortic regurgitation El Oumeiri, Bachar van de Borne, Philippe Hubesch, Géraldine Herpain, Antoine Annoni, Filippo Jespers, Pascale Stefanidis, Constantin Mc Entee, Kathleen Vanden Eynden, Frédéric Physiol Rep Original Articles In patients with chronic aortic regurgitation (AR), excessive preload and afterload increase left ventricle wall stress, leading to left ventricular systolic dysfunction. Thus, the objective of the present study was to evaluate the effects of the myosin activator omecamtiv mecarbil (OM) on left ventricle wall stress in an experimental rat model of severe chronic AR. Forty adult male Wistar rats were randomized into two experimental groups: induction of AR (acute phase) by retrograde puncture (n = 34) or a sham intervention (n = 6). Rats that survived the acute phase (n = 18) were randomized into an OM group (n = 8) or a placebo group (n = 10). Equal volumes of OM (1.2 mg/kg/h) or placebo (0.9% NaCl) were continuously infused into the femoral vein over 30 min. OM significantly decreased end‐systolic and end‐diastolic and maximum wall stress in this experimental rat model of chronic severe AR (p < 0.001) and increased systolic performance assessed by fractional shortening and left ventricle end‐systolic diameter; both p < 0.05). These effects were correlated with decreased indices of global cardiac function (cardiac output and stroke volume; p < 0.05) but were not inferior to baseline pump indices. Infusion with placebo did not affect global cardiac function but decreased end‐systolic wall stress (p < 0.05) and increased systolic performance (all p < 0.001). In the sham‐operated (control) group, OM decreased diastolic wall stress (p < 0.05). Based on these results, OM had a favorable effect on left ventricle wall stress in an experimental rat model of severe chronic AR. John Wiley and Sons Inc. 2021-08-17 /pmc/articles/PMC8371349/ /pubmed/34405966 http://dx.doi.org/10.14814/phy2.14988 Text en © 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://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
El Oumeiri, Bachar
van de Borne, Philippe
Hubesch, Géraldine
Herpain, Antoine
Annoni, Filippo
Jespers, Pascale
Stefanidis, Constantin
Mc Entee, Kathleen
Vanden Eynden, Frédéric
The myosin activator omecamtiv mecarbil improves wall stress in a rat model of chronic aortic regurgitation
title The myosin activator omecamtiv mecarbil improves wall stress in a rat model of chronic aortic regurgitation
title_full The myosin activator omecamtiv mecarbil improves wall stress in a rat model of chronic aortic regurgitation
title_fullStr The myosin activator omecamtiv mecarbil improves wall stress in a rat model of chronic aortic regurgitation
title_full_unstemmed The myosin activator omecamtiv mecarbil improves wall stress in a rat model of chronic aortic regurgitation
title_short The myosin activator omecamtiv mecarbil improves wall stress in a rat model of chronic aortic regurgitation
title_sort myosin activator omecamtiv mecarbil improves wall stress in a rat model of chronic aortic regurgitation
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371349/
https://www.ncbi.nlm.nih.gov/pubmed/34405966
http://dx.doi.org/10.14814/phy2.14988
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