Effects of the cardiac myosin activator Omecamtiv-mecarbil on severe chronic aortic regurgitation in Wistar rats
Abstract Background Aortic regurgitation (AR) is a valvular disease that can lead to systolic heart failure. Treatment options besides cardiac surgery are limited and consequently severe AR is associated with higher mortality and morbidity when not operated. In this investigation, we examined the ef...
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | BMC Cardiovascular Disorders |
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| Online Access: | http://link.springer.com/article/10.1186/s12872-018-0831-3 |
| _version_ | 1818981369252937728 |
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| author | Bachar El-Oumeiri Kathleen Mc Entee Filippo Annoni Antoine Herpain Frédéric Vanden Eynden Pascal Jespers Guido Van Nooten Philippe van de Borne |
| author_facet | Bachar El-Oumeiri Kathleen Mc Entee Filippo Annoni Antoine Herpain Frédéric Vanden Eynden Pascal Jespers Guido Van Nooten Philippe van de Borne |
| author_sort | Bachar El-Oumeiri |
| collection | DOAJ |
| description | Abstract Background Aortic regurgitation (AR) is a valvular disease that can lead to systolic heart failure. Treatment options besides cardiac surgery are limited and consequently severe AR is associated with higher mortality and morbidity when not operated. In this investigation, we examined the effects of a novel cardiac myosin activator, Omecamtiv-mecarbil (OM), in rats with chronic severe AR. Methods AR was created by retrograde puncture of the aortic valve leaflets in 20 adults Wistar rats. 12 animals survived the acute AR phase and were randomized 2 months thereafter into OM (n = 7) or placebo groups (n = 5). Two rats underwent a sham operation and served as controls. Equal volumes of OM or placebo (NaCl 0.9%) were perfused in the femoral vein by continuous infusion (1.2 mg/kg/hour) during 30 min. Doppler-echocardiography was performed before and at the end of the infusion periods. Results OM increased indices of global cardiac function (cardiac output, stroke volume), and increased systolic performance (fractional shortening, ejection fraction, left ventricular end systolic diameter) (all p < 0.05). These effects concurred with decreases in indices of LV preload (left atrial size, left ventricular end diastolic diameter) as well in the aortic pre-ejection period / left ventricular ejection time ratio (all p < 0.05). The severity score of the regurgitant AR jet did not change. Placebo infusion did not affect these parameters. Conclusion The cardiac myosin activator OM exerts favorable hemodynamic effects in rats with experimental chronic AR. |
| first_indexed | 2024-12-20T17:30:13Z |
| format | Article |
| id | doaj.art-e3b630e36f554e69aa110014e521eb37 |
| institution | Directory Open Access Journal |
| issn | 1471-2261 |
| language | English |
| last_indexed | 2024-12-20T17:30:13Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
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| series | BMC Cardiovascular Disorders |
| spelling | doaj.art-e3b630e36f554e69aa110014e521eb372022-12-21T19:31:25ZengBMCBMC Cardiovascular Disorders1471-22612018-05-011811910.1186/s12872-018-0831-3Effects of the cardiac myosin activator Omecamtiv-mecarbil on severe chronic aortic regurgitation in Wistar ratsBachar El-Oumeiri0Kathleen Mc Entee1Filippo Annoni2Antoine Herpain3Frédéric Vanden Eynden4Pascal Jespers5Guido Van Nooten6Philippe van de Borne7Department of Cardiac surgery, Erasme Hospital, ULBLaboratory of Physiology and Pharmacology, ULBDepartment of intensive care, Erasme Hospital, ULBDepartment of intensive care, Erasme Hospital, ULBDepartment of Cardiac surgery, Erasme Hospital, ULBLaboratory of Physiology and Pharmacology, ULBDepartment of Cardiac surgery, Erasme Hospital, ULBDepartment of Cardiology, Erasme Hospital, ULBAbstract Background Aortic regurgitation (AR) is a valvular disease that can lead to systolic heart failure. Treatment options besides cardiac surgery are limited and consequently severe AR is associated with higher mortality and morbidity when not operated. In this investigation, we examined the effects of a novel cardiac myosin activator, Omecamtiv-mecarbil (OM), in rats with chronic severe AR. Methods AR was created by retrograde puncture of the aortic valve leaflets in 20 adults Wistar rats. 12 animals survived the acute AR phase and were randomized 2 months thereafter into OM (n = 7) or placebo groups (n = 5). Two rats underwent a sham operation and served as controls. Equal volumes of OM or placebo (NaCl 0.9%) were perfused in the femoral vein by continuous infusion (1.2 mg/kg/hour) during 30 min. Doppler-echocardiography was performed before and at the end of the infusion periods. Results OM increased indices of global cardiac function (cardiac output, stroke volume), and increased systolic performance (fractional shortening, ejection fraction, left ventricular end systolic diameter) (all p < 0.05). These effects concurred with decreases in indices of LV preload (left atrial size, left ventricular end diastolic diameter) as well in the aortic pre-ejection period / left ventricular ejection time ratio (all p < 0.05). The severity score of the regurgitant AR jet did not change. Placebo infusion did not affect these parameters. Conclusion The cardiac myosin activator OM exerts favorable hemodynamic effects in rats with experimental chronic AR.http://link.springer.com/article/10.1186/s12872-018-0831-3Omecamtiv-mecarbilAortic regurgitationDoppler-echocardiographyWistar ratLeft ventricle |
| spellingShingle | Bachar El-Oumeiri Kathleen Mc Entee Filippo Annoni Antoine Herpain Frédéric Vanden Eynden Pascal Jespers Guido Van Nooten Philippe van de Borne Effects of the cardiac myosin activator Omecamtiv-mecarbil on severe chronic aortic regurgitation in Wistar rats BMC Cardiovascular Disorders Omecamtiv-mecarbil Aortic regurgitation Doppler-echocardiography Wistar rat Left ventricle |
| title | Effects of the cardiac myosin activator Omecamtiv-mecarbil on severe chronic aortic regurgitation in Wistar rats |
| title_full | Effects of the cardiac myosin activator Omecamtiv-mecarbil on severe chronic aortic regurgitation in Wistar rats |
| title_fullStr | Effects of the cardiac myosin activator Omecamtiv-mecarbil on severe chronic aortic regurgitation in Wistar rats |
| title_full_unstemmed | Effects of the cardiac myosin activator Omecamtiv-mecarbil on severe chronic aortic regurgitation in Wistar rats |
| title_short | Effects of the cardiac myosin activator Omecamtiv-mecarbil on severe chronic aortic regurgitation in Wistar rats |
| title_sort | effects of the cardiac myosin activator omecamtiv mecarbil on severe chronic aortic regurgitation in wistar rats |
| topic | Omecamtiv-mecarbil Aortic regurgitation Doppler-echocardiography Wistar rat Left ventricle |
| url | http://link.springer.com/article/10.1186/s12872-018-0831-3 |
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