Exercise Training Reveals Inflexibility of the Diaphragm in an Animal Model of Patients With Obesity‐Driven Heart Failure With a Preserved Ejection Fraction
BackgroundRespiratory muscle weakness contributes to exercise intolerance in patients with heart failure with a preserved ejection fraction (HFpEF)—a condition characterized by multiple comorbidities with few proven treatments. We aimed, therefore, to provide novel insight into the underlying diaphr...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2017-10-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.117.006416 |
| _version_ | 1811332626032623616 |
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| author | T. Scott Bowen Dominic Brauer Natale P. L. Rolim Fredrik H. Bækkerud Angela Kricke Anne‐Marie Ormbostad Berre Tina Fischer Axel Linke Gustavo Justo da Silva Ulrik Wisloff Volker Adams |
| author_facet | T. Scott Bowen Dominic Brauer Natale P. L. Rolim Fredrik H. Bækkerud Angela Kricke Anne‐Marie Ormbostad Berre Tina Fischer Axel Linke Gustavo Justo da Silva Ulrik Wisloff Volker Adams |
| author_sort | T. Scott Bowen |
| collection | DOAJ |
| description | BackgroundRespiratory muscle weakness contributes to exercise intolerance in patients with heart failure with a preserved ejection fraction (HFpEF)—a condition characterized by multiple comorbidities with few proven treatments. We aimed, therefore, to provide novel insight into the underlying diaphragmatic alterations that occur in HFpEF by using an obese cardiometabolic rat model and further assessed whether exercise training performed only after the development of overt HFpEF could reverse impairments. Methods and ResultsObese ZSF1 rats (n=12) were compared with their lean controls (n=8) at 20 weeks, with 3 additional groups of obese ZSF1 rats compared at 28 weeks following 8 weeks of either sedentary behavior (n=13), high‐intensity interval training (n=11), or moderate‐continuous training (n=11). Obese rats developed an obvious HFpEF phenotype at 20 and 28 weeks. In the diaphragm at 20 weeks, HFpEF induced a shift towards an oxidative phenotype and a fiber hypertrophy paralleled by a lower protein expression in MuRF1 and MuRF2, yet mitochondrial and contractile functional impairments were observed. At 28 weeks, neither the exercise training regimen of high‐intensity interval training or moderate‐continuous training reversed any of the diaphragm alterations induced by HFpEF. ConclusionsThis study, using a well‐characterized rat model of HFpEF underpinned by multiple comorbidities and exercise intolerance (ie, one that closely resembles the patient phenotype), provides evidence that diaphragm alterations and dysfunction induced in overt HFpEF are not reversed following 8 weeks of aerobic exercise training. As such, whether alternative therapeutic interventions are required to treat respiratory muscle weakness in HFpEF warrants further investigation. |
| first_indexed | 2024-04-13T16:39:47Z |
| format | Article |
| id | doaj.art-32678be3cc1643a88b943274b7b9747f |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-13T16:39:47Z |
| publishDate | 2017-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-32678be3cc1643a88b943274b7b9747f2022-12-22T02:39:16ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802017-10-0161010.1161/JAHA.117.006416Exercise Training Reveals Inflexibility of the Diaphragm in an Animal Model of Patients With Obesity‐Driven Heart Failure With a Preserved Ejection FractionT. Scott Bowen0Dominic Brauer1Natale P. L. Rolim2Fredrik H. Bækkerud3Angela Kricke4Anne‐Marie Ormbostad Berre5Tina Fischer6Axel Linke7Gustavo Justo da Silva8Ulrik Wisloff9Volker Adams10Department of Internal Medicine and Cardiology, Leipzig University‐Heart Center, Leipzig, GermanyDepartment of Internal Medicine and Cardiology, Leipzig University‐Heart Center, Leipzig, GermanyK.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, NorwayK.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, NorwayDepartment of Internal Medicine and Cardiology, Leipzig University‐Heart Center, Leipzig, GermanyK.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, NorwayDepartment of Internal Medicine and Cardiology, Leipzig University‐Heart Center, Leipzig, GermanyDepartment of Internal Medicine and Cardiology, Leipzig University‐Heart Center, Leipzig, GermanyK.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, NorwayK.G. Jebsen Center of Exercise in Medicine, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, NorwayDepartment of Internal Medicine and Cardiology, Leipzig University‐Heart Center, Leipzig, GermanyBackgroundRespiratory muscle weakness contributes to exercise intolerance in patients with heart failure with a preserved ejection fraction (HFpEF)—a condition characterized by multiple comorbidities with few proven treatments. We aimed, therefore, to provide novel insight into the underlying diaphragmatic alterations that occur in HFpEF by using an obese cardiometabolic rat model and further assessed whether exercise training performed only after the development of overt HFpEF could reverse impairments. Methods and ResultsObese ZSF1 rats (n=12) were compared with their lean controls (n=8) at 20 weeks, with 3 additional groups of obese ZSF1 rats compared at 28 weeks following 8 weeks of either sedentary behavior (n=13), high‐intensity interval training (n=11), or moderate‐continuous training (n=11). Obese rats developed an obvious HFpEF phenotype at 20 and 28 weeks. In the diaphragm at 20 weeks, HFpEF induced a shift towards an oxidative phenotype and a fiber hypertrophy paralleled by a lower protein expression in MuRF1 and MuRF2, yet mitochondrial and contractile functional impairments were observed. At 28 weeks, neither the exercise training regimen of high‐intensity interval training or moderate‐continuous training reversed any of the diaphragm alterations induced by HFpEF. ConclusionsThis study, using a well‐characterized rat model of HFpEF underpinned by multiple comorbidities and exercise intolerance (ie, one that closely resembles the patient phenotype), provides evidence that diaphragm alterations and dysfunction induced in overt HFpEF are not reversed following 8 weeks of aerobic exercise training. As such, whether alternative therapeutic interventions are required to treat respiratory muscle weakness in HFpEF warrants further investigation.https://www.ahajournals.org/doi/10.1161/JAHA.117.006416diastolic heart failuremetabolismobesityrespiratory muscleskeletal muscle exerciseZSF1 |
| spellingShingle | T. Scott Bowen Dominic Brauer Natale P. L. Rolim Fredrik H. Bækkerud Angela Kricke Anne‐Marie Ormbostad Berre Tina Fischer Axel Linke Gustavo Justo da Silva Ulrik Wisloff Volker Adams Exercise Training Reveals Inflexibility of the Diaphragm in an Animal Model of Patients With Obesity‐Driven Heart Failure With a Preserved Ejection Fraction Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease diastolic heart failure metabolism obesity respiratory muscle skeletal muscle exercise ZSF1 |
| title | Exercise Training Reveals Inflexibility of the Diaphragm in an Animal Model of Patients With Obesity‐Driven Heart Failure With a Preserved Ejection Fraction |
| title_full | Exercise Training Reveals Inflexibility of the Diaphragm in an Animal Model of Patients With Obesity‐Driven Heart Failure With a Preserved Ejection Fraction |
| title_fullStr | Exercise Training Reveals Inflexibility of the Diaphragm in an Animal Model of Patients With Obesity‐Driven Heart Failure With a Preserved Ejection Fraction |
| title_full_unstemmed | Exercise Training Reveals Inflexibility of the Diaphragm in an Animal Model of Patients With Obesity‐Driven Heart Failure With a Preserved Ejection Fraction |
| title_short | Exercise Training Reveals Inflexibility of the Diaphragm in an Animal Model of Patients With Obesity‐Driven Heart Failure With a Preserved Ejection Fraction |
| title_sort | exercise training reveals inflexibility of the diaphragm in an animal model of patients with obesity driven heart failure with a preserved ejection fraction |
| topic | diastolic heart failure metabolism obesity respiratory muscle skeletal muscle exercise ZSF1 |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.117.006416 |
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