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Heart Failure with Preserved Ejection Fraction Induces Molecular, Mitochondrial, Histological, and Functional Alterations in Rat Diaphragm Muscle
Author(s) -
Bowen T Scott,
Rolim Natale,
Fischer Tina,
Bækkerud Fredrik,
Medeiros Alessandra,
Werner Sarah,
Bronstad Eivind,
Rognmo Oivind,
Mangner Norman,
Linke Axel,
Schuler Gerhard,
Silva Gustavo,
Wisloff Ulrik,
Adams Volker
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1013.3
Subject(s) - heart failure with preserved ejection fraction , medicine , exercise intolerance , heart failure , cardiology , muscle hypertrophy , endocrinology , diaphragm (acoustics) , ejection fraction , skeletal muscle , diastole , blood pressure , physics , acoustics , loudspeaker
Peripheral muscle dysfunction is a key mechanism contributing to exercise intolerance in heart failure patients with preserved ejection fraction (HFpEF), however the underlying mechanisms remain unknown. We used an animal model to better understand potential molecular, mitochondrial, histological, and functional alterations induced by HFpEF in the diaphragm. Methods Female Dahl salt‐sensitive rats were fed a low‐ or high‐salt diet of 0.3% or 8% NaCL for 28 weeks. Heart function and diaphragm alterations were subsequently assessed. Results Compared to low‐salt rats (CON; n=10), high‐salt rats (n=11) developed HFpEF, as demonstrated by impaired diastolic function, preserved left ventricular EF, left ventricular hypertrophy, elevated systolic blood pressure, increased pulmonary congestion, and elevated plasma natriuretic peptides (P<0.05). HFpEF rat diaphragm demonstrated (P<0.05): 1) a fiber type distribution shift from fast‐to‐slow twitch; 2) a decreased pro‐oxidative but increased anti‐oxidant capacity; 3) reduced proteasome activation; 4) impaired in situ mitochondrial respiration at complex I: 5) in vitro muscle weakness and increased fatigability in fiber bundles. Conclusion These data suggest a skeletal muscle myopathy exists in HFpEF and identifies novel mechanisms of exercise intolerance in HFpEF.