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Skeletal muscle mitochondrial dysfunction in pacing‐induced heart failure in dogs
Author(s) -
Rosca Mariana G,
Vazquez Edwin J,
Stanley William,
Hoppel Charles L
Publication year - 2006
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.20.4.a801-b
Subject(s) - heart failure , skeletal muscle , medicine , cardiology
Mitochondrial dysfunction may be the common signaling mechanism in the evolution of heart failure and the related skeletal myopathy. Previous studies reported a decrease in mitochondrial complex III and V activities when measured in cardiac and skeletal homogenates from pacing‐induced heart failure dogs. Our strategy to focus on isolated mitochondria was based on the hypothesis that the two skeletal muscle populations of mitochondria (subsarcolemmal‐SSM and intermyofibrillar‐IFM) differ in their response to heart failure via their accessibility and reply to plasma and tissue inflammatory cytokines. Therefore we have examined the SSM and IFM isolated from gastrocnemius of control and pacing‐induced heart failure dogs. SSM isolated from heart failure dogs displayed a decrease in oxidation of substrates that supply the electron transport chain upstream of complex IV. Specifically, the decline in duroquinol‐supplied respiration (a complex III substrate) associated with normal TMPD‐dependent respiration (complex IV substrate) in SSM is a strong indication of a complex III defect. Measurement of the enzymatic activities of mitochondrial respiratory complexes confirmed the selective decline in complex III activity in the SSM. Identification of the mechanism(s) responsible for mitochondrial defect will provide further insight into the treatment of the heart failure related myopathy. Supported by NIH grants to CLH.