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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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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. |
format | Online Article Text |
id | pubmed-8371349 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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