{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:48:55Z","timestamp":1791668935598,"version":"4.3.4"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,10,11]]},"abstract":"\n Background<\/jats:title>\n \n Respiratory muscle weakness contributes to exercise intolerance in patients with heart failure with a preserved ejection fraction (\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n )\u2014a condition characterized by multiple comorbidities with few proven treatments. We aimed, therefore, to provide novel insight into the underlying diaphragmatic alterations that occur in\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n by using an obese cardiometabolic rat model and further assessed whether exercise training performed only after the development of overt\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n could reverse impairments.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Obese\n ZSF<\/jats:styled-content>\n 1 rats (n=12) were compared with their lean controls (n=8) at 20\u00a0weeks, with 3 additional groups of obese\n ZSF<\/jats:styled-content>\n 1 rats compared at 28\u00a0weeks following 8\u00a0weeks of either sedentary behavior (n=13), high\u2010intensity interval training (n=11), or moderate\u2010continuous training (n=11). Obese rats developed an obvious\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n phenotype at 20 and 28\u00a0weeks. In the diaphragm at 20\u00a0weeks,\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n induced a shift towards an oxidative phenotype and a fiber hypertrophy paralleled by a lower protein expression in Mu\n RF<\/jats:styled-content>\n 1 and MuRF2, yet mitochondrial and contractile functional impairments were observed. At 28\u00a0weeks, neither the exercise training regimen of high\u2010intensity interval training or moderate\u2010continuous training reversed any of the diaphragm alterations induced by\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n This study, using a well\u2010characterized rat model of\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n 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\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n are not reversed following 8\u00a0weeks of aerobic exercise training. As such, whether alternative therapeutic interventions are required to treat respiratory muscle weakness in\n HF<\/jats:styled-content>\n p\n EF<\/jats:styled-content>\n warrants further investigation.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.117.006416","type":"journal-article","created":{"date-parts":[[2017,10,25]],"date-time":"2017-10-25T00:10:34Z","timestamp":1508890234000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":45,"title":["Exercise Training Reveals Inflexibility of the Diaphragm in an Animal Model of Patients With Obesity\u2010Driven Heart Failure With a Preserved Ejection Fraction"],"prefix":"10.1161","volume":"6","author":[{"given":"T. Scott","family":"Bowen","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Leipzig University\u2010Heart Center, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic","family":"Brauer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Leipzig University\u2010Heart Center, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natale P. L.","family":"Rolim","sequence":"additional","affiliation":[{"name":"K.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, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik H.","family":"B\u00e6kkerud","sequence":"additional","affiliation":[{"name":"K.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, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Kricke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Leipzig University\u2010Heart Center, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Marie","family":"Ormbostad Berre","sequence":"additional","affiliation":[{"name":"K.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, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Leipzig University\u2010Heart Center, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Linke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Leipzig University\u2010Heart Center, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo Justo","family":"da Silva","sequence":"additional","affiliation":[{"name":"K.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, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrik","family":"Wisloff","sequence":"additional","affiliation":[{"name":"K.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, Norway"},{"name":"School of Human Movement & Nutrition Sciences, University of Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Adams","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Leipzig University\u2010Heart Center, Leipzig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2013.10.006"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/2047487314564729"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.302922"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.021884"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.114.001615"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.126.3.838"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2015.10.010"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.239"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2015.10.007"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.113.000539"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00076.2015"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.115.002760"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201600672r"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-016-9549-4"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.116.003027"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1994.77.5.2250"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1996.81.3.1347"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.79.1.147"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2000.89.2.695"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601952"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.11.049"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01177.2013"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2008.12.042"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1989.67.5.1807"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2016.03.011"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01123.2014"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00469.2015"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.117.006416","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T10:47:44Z","timestamp":1715597264000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.117.006416"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,11]]},"references-count":27,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2017,10,11]]}},"alternative-id":["10.1161\/JAHA.117.006416"],"URL":"https:\/\/doi.org\/10.1161\/jaha.117.006416","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,11]]},"assertion":[{"value":"2017-04-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-07-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-10-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e006416"}}