Quadriceps exercise intolerance in patients with chronic obstructive pulmonary disease: the potential role of altered skeletal muscle mitochondrial respiration.
This study sought to determine if qualitative alterations in skeletal muscle mitochondrial respiration, associated with decreased mitochondrial efficiency, contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). Using permeabilized muscle fibers from the vastus lateralis of 13 patients with COPD and 12 healthy controls, complex I (CI) and complex II (CII)-driven State 3 mitochondrial respiration were measured separately (State 3:CI and State 3:CII) and in combination (State 3:CI+CII). State 2 respiration was also measured. Exercise tolerance was assessed by knee extensor exercise (KE) time to fatigue. Per milligram of muscle, State 3:CI+CII and State 3:CI were reduced in COPD (P < 0.05), while State 3:CII and State 2 were not different between groups. To determine if this altered pattern of respiration represented qualitative changes in mitochondrial function, respiration states were examined as percentages of peak respiration (State 3:CI+CII), which revealed altered contributions from State 3:CI (Con 83.7 ± 3.4, COPD 72.1 ± 2.4%Peak, P < 0.05) and State 3:CII (Con 64.9 ± 3.2, COPD 79.5 ± 3.0%Peak, P < 0.05) respiration, but not State 2 respiration in COPD. Importantly, a diminished contribution of CI-driven respiration relative to the metabolically less-efficient CII-driven respiration (CI/CII) was also observed in COPD (Con 1.28 ± 0.09, COPD 0.81 ± 0.05, P < 0.05), which was related to exercise tolerance of the patients (r = 0.64, P < 0.05). Overall, this study indicates that COPD is associated with qualitative alterations in skeletal muscle mitochondria that affect the contribution of CI and CII-driven respiration, which potentially contributes to the exercise intolerance associated with this disease.
Geriatric Research, Education, and Clinical Center, Salt Lake City Veterans Affairs Medical Center, Salt Lake City, Utah; Department of Exercise and Sport Science, University of Utah, Salt Lake City, Utah;
Jayson R
JR
Gifford
Geriatric Research, Education, and Clinical Center, Salt Lake City Veterans Affairs Medical Center, Salt Lake City, Utah; Department of Internal Medicine, University of Utah, Salt Lake City, Utah; and.
Joel D
JD
Trinity
Geriatric Research, Education, and Clinical Center, Salt Lake City Veterans Affairs Medical Center, Salt Lake City, Utah; Department of Internal Medicine, University of Utah, Salt Lake City, Utah; and.
Gwenael
G
Layec
Geriatric Research, Education, and Clinical Center, Salt Lake City Veterans Affairs Medical Center, Salt Lake City, Utah; Department of Internal Medicine, University of Utah, Salt Lake City, Utah; and.
Ryan S
RS
Garten
Geriatric Research, Education, and Clinical Center, Salt Lake City Veterans Affairs Medical Center, Salt Lake City, Utah; Department of Exercise and Sport Science, University of Utah, Salt Lake City, Utah;
Song-Young
SY
Park
Geriatric Research, Education, and Clinical Center, Salt Lake City Veterans Affairs Medical Center, Salt Lake City, Utah; Department of Exercise and Sport Science, University of Utah, Salt Lake City, Utah;
Matthew J
MJ
Rossman
Xlab, Center for Healthy Aging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Steen
S
Larsen
Xlab, Center for Healthy Aging, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Flemming
F
Dela
Geriatric Research, Education, and Clinical Center, Salt Lake City Veterans Affairs Medical Center, Salt Lake City, Utah; Department of Exercise and Sport Science, University of Utah, Salt Lake City, Utah; Department of Internal Medicine, University of Utah, Salt Lake City, Utah; and r.richardson@hsc.utah.edu.
Russell S
RS
Richardson
D000368:Aged; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D017079:Exercise Tolerance / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000503:physiopathology*; D052097:Quadriceps Muscle / Q000378:metabolism / Q000503:physiopathology*
D042963:Electron Transport Complex II; D042967:Electron Transport Complex I
COPD; exercise intolerance; mitochondrial dysfunction; mitochondrial respiration; muscle dysfunction