Levosimendan, milrinone, and dobutamine in experimental acute pulmonary embolism
Acute pulmonary embolism is a frequent condition in emergency medicine and potentially fatal. Cause of death is right ventricular failure due to increased right ventricular afterload from both pulmonary vascular obstruction and vasoconstriction. Inodilators are interesting drugs of choice as they ma...
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| Format: | Article |
| Language: | English |
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Wiley
2021-07-01
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| Series: | Pulmonary Circulation |
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| Online Access: | https://doi.org/10.1177/20458940211022977 |
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| author | Mads D. Lyhne Simone J. Dragsbaek Jacob V. Hansen Jacob G. Schultz Asger Andersen Jens Erik Nielsen‐Kudsk |
| author_facet | Mads D. Lyhne Simone J. Dragsbaek Jacob V. Hansen Jacob G. Schultz Asger Andersen Jens Erik Nielsen‐Kudsk |
| author_sort | Mads D. Lyhne |
| collection | DOAJ |
| description | Acute pulmonary embolism is a frequent condition in emergency medicine and potentially fatal. Cause of death is right ventricular failure due to increased right ventricular afterload from both pulmonary vascular obstruction and vasoconstriction. Inodilators are interesting drugs of choice as they may improve right ventricular function and lower its afterload. We aimed to investigate the cardiovascular effects of three clinically relevant inodilators: levosimendan, milrinone, and dobutamine in acute pulmonary embolism. We conducted a randomized, blinded, animal study using 18 female pigs. Animals received large autologous pulmonary embolism until doubling of baseline mean pulmonary arterial pressure and were randomized to increasing doses of each inodilator. Effects were evaluated with bi‐ventricular pressure–volume loop recordings, right heart catheterization, and blood gas analyses. Induction of pulmonary embolism increased right ventricular afterload and pulmonary pressure (p < 0.05) causing right ventricular dysfunction. Levosimendan and milrinone showed beneficial hemodynamic profiles by lowering right ventricular pressures and volume (p < 0.001) and improved right ventricular function and cardiac output (p < 0.05) without increasing right ventricular mechanical work. Dobutamine increased right ventricular pressure and function (p < 0.01) but at a cost of increased mechanical work at the highest doses, showing an adverse hemodynamic profile. In a porcine model of acute pulmonary embolism, levosimendan and milrinone reduced right ventricular afterload and improved right ventricular function, whereas dobutamine at higher doses increased right ventricular afterload and right ventricular mechanical work. The study motivates clinical testing of inodilators in patients with acute pulmonary embolism and right ventricular dysfunction. |
| format | Article |
| id | doaj-art-8697190623b9485a93b1e3a1dce3b5ff |
| institution | OA Journals |
| issn | 2045-8940 |
| language | English |
| publishDate | 2021-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pulmonary Circulation |
| spelling | doaj-art-8697190623b9485a93b1e3a1dce3b5ff2025-08-20T02:27:31ZengWileyPulmonary Circulation2045-89402021-07-0111311110.1177/20458940211022977Levosimendan, milrinone, and dobutamine in experimental acute pulmonary embolismMads D. Lyhne0Simone J. Dragsbaek1Jacob V. Hansen2Jacob G. Schultz3Asger Andersen4Jens Erik Nielsen‐Kudsk5Department of CardiologyAarhus University Hospital, Aarhus, DenmarkDepartment of Clinical MedicineAarhus UniversityAarhusDenmarkDepartment of CardiologyAarhus University Hospital, Aarhus, DenmarkDepartment of Clinical MedicineAarhus UniversityAarhusDenmarkDepartment of CardiologyAarhus University Hospital, Aarhus, DenmarkDepartment of Clinical MedicineAarhus UniversityAarhusDenmarkDepartment of CardiologyAarhus University Hospital, Aarhus, DenmarkDepartment of Clinical MedicineAarhus UniversityAarhusDenmarkDepartment of CardiologyAarhus University Hospital, Aarhus, DenmarkDepartment of Clinical MedicineAarhus UniversityAarhusDenmarkDepartment of CardiologyAarhus University Hospital, Aarhus, DenmarkDepartment of Clinical MedicineAarhus UniversityAarhusDenmarkAcute pulmonary embolism is a frequent condition in emergency medicine and potentially fatal. Cause of death is right ventricular failure due to increased right ventricular afterload from both pulmonary vascular obstruction and vasoconstriction. Inodilators are interesting drugs of choice as they may improve right ventricular function and lower its afterload. We aimed to investigate the cardiovascular effects of three clinically relevant inodilators: levosimendan, milrinone, and dobutamine in acute pulmonary embolism. We conducted a randomized, blinded, animal study using 18 female pigs. Animals received large autologous pulmonary embolism until doubling of baseline mean pulmonary arterial pressure and were randomized to increasing doses of each inodilator. Effects were evaluated with bi‐ventricular pressure–volume loop recordings, right heart catheterization, and blood gas analyses. Induction of pulmonary embolism increased right ventricular afterload and pulmonary pressure (p < 0.05) causing right ventricular dysfunction. Levosimendan and milrinone showed beneficial hemodynamic profiles by lowering right ventricular pressures and volume (p < 0.001) and improved right ventricular function and cardiac output (p < 0.05) without increasing right ventricular mechanical work. Dobutamine increased right ventricular pressure and function (p < 0.01) but at a cost of increased mechanical work at the highest doses, showing an adverse hemodynamic profile. In a porcine model of acute pulmonary embolism, levosimendan and milrinone reduced right ventricular afterload and improved right ventricular function, whereas dobutamine at higher doses increased right ventricular afterload and right ventricular mechanical work. The study motivates clinical testing of inodilators in patients with acute pulmonary embolism and right ventricular dysfunction.https://doi.org/10.1177/20458940211022977right ventricular functioninodilatorpulmonary circulationanimal modelpressure–volume loops |
| spellingShingle | Mads D. Lyhne Simone J. Dragsbaek Jacob V. Hansen Jacob G. Schultz Asger Andersen Jens Erik Nielsen‐Kudsk Levosimendan, milrinone, and dobutamine in experimental acute pulmonary embolism Pulmonary Circulation right ventricular function inodilator pulmonary circulation animal model pressure–volume loops |
| title | Levosimendan, milrinone, and dobutamine in experimental acute pulmonary embolism |
| title_full | Levosimendan, milrinone, and dobutamine in experimental acute pulmonary embolism |
| title_fullStr | Levosimendan, milrinone, and dobutamine in experimental acute pulmonary embolism |
| title_full_unstemmed | Levosimendan, milrinone, and dobutamine in experimental acute pulmonary embolism |
| title_short | Levosimendan, milrinone, and dobutamine in experimental acute pulmonary embolism |
| title_sort | levosimendan milrinone and dobutamine in experimental acute pulmonary embolism |
| topic | right ventricular function inodilator pulmonary circulation animal model pressure–volume loops |
| url | https://doi.org/10.1177/20458940211022977 |
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