The long-term goal of this research is to improve mobility, functional independence, and
quality of life in patients with peripheral artery disease (PAD) by developing
conservative interventions. PAD is a manifestation of atherosclerosis, which produces
blockages in the leg arteries, and results in insufficient blood flow to the legs. PAD
results in significant gait deficits and an overall sedentary lifestyle. The
investigators' prior work showed that the biochemical (oxidative stress and mitochondrial
dysfunction) and histological (myofiber degeneration and fibrosis) characteristics of PAD
muscles are altered compared to controls. These myopathic changes are due to cycles of
ischemia and reperfusion, and they correlate to functional limitations (walking distance
and calf muscle strength). Limb ischemia from PAD is the most common disorder treated
within the vascular surgery service of the Omaha Veterans Affairs Medical Center. The
most effective treatment for increasing the distances that patients with PAD can walk is
supervised exercise therapy (SET). However, SET uses pain onset to guide exercise
intensity and rest cycles. These repeated bouts of ischemia/reperfusion could cause
further pathological damage to muscle myofibers and oxidative processes. Such adverse
effects of ischemia may explain why not all patients improve with SET. Preventing cycles
of ischemia-reperfusion during SET can improve walking performance without further muscle
biochemistry damage in patients with PAD. The investigators propose using hemodynamic
responses to modulate exercise intensity and prevent ischemia during SET. Muscle
oxygen-guided supervised exercise therapy (M-SET) can prevent ischemia onset and thus
preserve muscle mass and function during exercise therapy in patients with PAD. The aims
are:
Aim 1: To determine the exercise outcomes of an M-SET versus a standard SET session in
patients with PAD. Aim 2: To determine the acute effect of M-SET versus standard SET on
oxidative stress and inflammation in patients with PAD. Aim 3: To determine the effect of
12 weeks of M-SET versus standard SET on exercise outcomes, muscle biochemistry, and
subject-reported preference in patients with PAD.
The investigators will measure exercise outcomes during one session each of M-SET (using
StO2 on the calf to modulate exercise) and SET, in 12 patients with PAD using a
cross-over design. Exercise outcomes will be assessed by the total distance patients
walked during the session, metabolic cost, metabolic equivalents of the task, physical
activity enjoyment, and rate of perceived exertion. In Aim 2, oxidative stress will be
measured using peripheral blood mononuclear cells before and after each exercise session
(SET and M-SET) in all patients. During the standard SET session, subjects will walk
until claudication pain becomes severe and the participant needs to stop. Then subjects
will rest until claudication pain subsides. Afterward, subjects will walk again,
repeating the cycle for up to 50 minutes. M-SET will use an StO2 threshold that is 15%
lower level than baseline StO2 levels. Subjects will stop walking once they reach the
threshold and rest until StO2 levels return to baseline. Then, subjects will begin
walking again, repeating this cycle for 50 total minutes (including walking and rest).
Patients from Aims 1 and 2 will be randomly assigned to either a 12-week M-SET or
standard SET (6 per group) program. Training will be performed three times weekly as
described above. Subjects will be evaluated before and after the intervention to capture
initial and absolute walking distances and 7-day physical activity. Muscle biochemistry
will be quantified using mitochondrial function, mitochondrial oxidative dynamics, and
reactive oxygen species production before and after training. Results will support a full
clinical trial and rehabilitation recommendations.