Bowen 2017 J Am Heart Assoc
|Bowen TS, Brauer D, Rolim NPL, Bækkerud FH, Kricke A, Ormbostad Berre AM, Fischer T, Linke A, da Silva GJ, Wisloff U, Adams V (2017) Exercise training reveals inflexibility of the diaphragm in an animal model of patients with obesity-driven heart failure with a preserved ejection fraction. J Am Heart Assoc 6. pii: e006416.|
Abstract: Respiratory 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.
Obese 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.
This 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.
© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. • Keywords: ZSF1, Diastolic heart failure, Metabolism, Obesity, Respiratory muscle, Skeletal muscle exercise • Bioblast editor: Kandolf G • O2k-Network Lab: NO Trondheim Rognmo O
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style Pathology: Cardiovascular, Obesity
Organism: Rat Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS Pathway: N, NS HRR: Oxygraph-2k
Labels, 2018-01, Comorbidity