REDUCED MECHANICAL EFFICIENCY IN COPD,
BUT NORMAL PEAK VO2 WITH SMALL MUSCLE MASS EXERCISE
"This article has an online data supplement, which is accessible from this issue's table of content
online at www.atsjournals.com"
Authors: Russell S. Richardson
Bryan T. Leek
Timothy P. Gavin
Luke J. Haseler
Sundar R.D. Mudaliar
Andrew L. Ries
Odile D. Mathieu-Costello
Peter D. Wagner
Institution:Department of Medicine,
University of California San Diego,
La Jolla, CA 92093.
Dr. R.S. Richardson
Department of Medicine, 0623
University of California San Diego,
La Jolla, CA 92093-0623
TEL: (858) 534-9841
FAX: (858) 534-4812
Running Head: COPD and skeletal muscle function.
Word count: 7,176
Subject Category Number: 53 COPD: Pathophysiology
Copyright (C) 2003 by the American Thoracic Society.
AJRCCM Articles in Press. Published on September 18, 2003 as doi:10.1164/rccm.200305-627OC
We studied 6 patients with COPD (FEV1 = 1.1 ± 0.2 L, 32% of predicted) and 6 age and
activity level matched controls while performing both maximal bicycle exercise and
single leg knee-extensor exercise. Arterial and femoral venous blood sampling,
thermodilution blood flow measurements and needle biopsies allowed the assessment of
muscle O2 supply, utilization and structure. Maximal work rates and single leg maximal
oxygen consumption (controls = 0.63 ± 0.1; COPD = 0.37 ± 0.1 l/min) were significantly
greater in the control group during bicycle exercise. During knee-extensor exercise this
difference in maximal oxygen consumption disappeared, while maximal work capacity
was reduced (flywheel resistance: controls = 923 ± 198; COPD = 612 ± 81 g) revealing a
significantly reduced mechanical efficiency (work per unit O2 consumed) with COPD.
The patients had an elevated number of less efficient Type II muscle fibers while muscle
fiber cross sectional areas, capillarity and mitochondrial volume density were not
different between the groups. Therefore although metabolic capacity per se is unchanged,
fiber type differences associated with COPD may account for the reduced muscular
mechanical efficiency that becomes clearly apparent during knee-extensor exercise, when
muscle is no longer overshadowed by the decrement in lung function.
Word Count 200
KEY WORDS: lung disease, Oxygen consumption, blood flow, fiber type, quadriceps
Although researchers have recently focused their attention on the potential involvement
of skeletal muscle in the pathophysiology of COPD (7, 28, 32, 35, 41) there is currently no
accord on this matter (1). An issue that has clouded conclusions is the difference between
skeletal muscle dysfunction and disuse (52). Certainly, patients with COPD experience
locomotor muscle disuse, promoted by the dyspnea that accompanies exercise in this condition.
However, should simply deconditioned skeletal muscle be considered dysfunctional? The
tendency to answer yes to this question has been promoted by studies that magnify the
differences in COPD skeletal muscle by comparisons with relatively physically active control
subjects (32, 33, 52, 67). Thus, the selection of appropriately inactive controls becomes an
essential component of the experimental design of research focused on the assessment of skeletal
muscle function and COPD.
Additional support for the concept of dysfunctional muscle in COPD has been provided
by the regular use of whole body exercise, such as cycling, to evaluate muscle function (32, 35,
64). The use of a large muscle mass exercise paradigm, in COPD patients, may shroud peripheral
muscle limitations by the attainment of a patient’s reduced ventilation ceiling, before truly taxing
the locomotor muscles. Ideally, to study muscle function itself in COPD, the amount of muscle
recruited should be small enough that the patient can achieve maximal muscular work before the
influence of central ventilatory limitations.
The single leg knee-extensor exercise model (3), allows the measurement of O2 supply
and utilization to a known mass of active muscle (53) under conditions of limited ventilatory
demand, and thus is an ideal exercise paradigm with which to study the skeletal muscle of
patients with COPD (59). The ability to monitor muscle O2 supply in this paradigm is essential,
because without this, metabolic differences may be the consequence of either intrinsic muscle
dysfunction or the normal response of healthy (even if detrained) muscle to reduced O2 supply.
Consequently, this study was designed to assess skeletal muscle function in patients with
COPD during both cycle and single leg knee-extensor exercise in comparison to healthy control
subjects that were well-matched, both in terms of physical activity and physical characteristics.
The purpose of this study was to test the following hypotheses: 1) during cycle exercise the
skeletal muscle of patients with COPD will appear dysfunctional in comparison to controls in
terms of maximal work rate, muscle blood flow, and VO2, while 2) during single leg knee-
extensor exercise the skeletal muscle of patients with COPD will have a more similar
physiological response to that of the control subjects. This work has been previously published in
abstract form (51).
Subjects: Six patients with COPD (FEV1= 1.1 ±0.2, 32 ± 5% predicted )(11) and six
healthy age, weight and activity matched controls volunteered according to the University of
California San Diego, Human Research Protection Program requirements. Controls were
determined to be sedentary and the majority of the COPD patients had completed the UCSD
Pulmonary Rehabilitation Program (within 8-24 months), but did not differ from the controls in
terms of current physical activity (13, 23, 70). Subject characteristics are presented in Table 1.
Exercise models: Two exercise modalities were employed in this study the first being
conventional bicycle ergometry performed on an electrically braked bike (Excalibur, Quinton
Instruments Company, Holland). Cadence was self selected, but for most subjects fell between
60-80 revolutions per minute. The second exercise paradigm was knee-extensor exercise, that
limits muscular work to the quadriceps of one leg (3, 53, 58), this was performed with subjects
reclined on a padded chair with the knee-extensor exercise ergometer placed in front of them
(illustrated in Reference (57)) (see online supplement).
Experimental protocol: Within 1 wk of preliminary familiarization studies, subjects
returned to the laboratory where two catheters (radial artery and left femoral vein) and a
thermocouple (left femoral vein) were emplaced using sterile technique as previously reported
(49, 58)(see online supplement). Blood samples were taken from the arterial and femoral venous
catheters to quantify arterial-venous O2 concentration differences.
Following the catheterization procedures two bouts of graded exercise were performed: 1)
conventional cycle exercise and 2) single leg knee-extensor exercise. The order of these exercise
bouts across subjects was balanced to avoid potential ordering effects. For each exercise bout,
the work rate was increased from an unweighted warm-up to the previously determined