Walking Exercise Therapy Effects on Lower Extremity Skeletal Muscle in Peripheral Artery Disease.
Study Goal
The researchers aimed to understand the biological mechanisms by which walking exercise improves walking ability in people with peripheral artery disease (PAD) and how these mechanisms differ from those in people without PAD.
Results Summary
Walking exercise improved treadmill walking time in PAD patients but also increased muscle denervation markers. Exercise did not consistently improve mitochondrial activity or capillary density in PAD patients, though it may enhance plasma nitrite levels, potentially improving muscle perfusion.
Population
Older individuals with peripheral artery disease (PAD).
Effective Dosage
Not specified (supervised treadmill exercise).
Duration
12 weeks (in one randomized trial).
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
Walking exercise | increase | walking ability | peripheral artery disease (PAD) | - | is the most effective noninvasive therapy that improves | #1 |
aerobic exercise | increase | mitochondrial activity, muscle mass, capillary density, and insulin sensitivity | older people without PAD | - | improves | #2 |
walking exercise | increase | lower extremity ischemia | people with PAD | - | increases | #3 |
- | increase | mitochondrial impairment, increased reactive oxygen species, and increased fibrosis | gastrocnemius muscle in people with PAD compared with people without PAD | - | has greater | #4 |
walking exercise therapy | no change | mitochondrial activity | people with PAD | - | did not consistently improve | #5 |
supervised treadmill exercise | increase | treadmill walking time | people with PAD randomized to supervised exercise | from 9.3 to 15.1 minutes | increased | #6 |
supervised treadmill exercise | increase | proportion of angular muscle fibers | people with PAD randomized to supervised exercise | from 7.6% to 15.6% | increased | #7 |
- | no change | angular myofibers | control group | from 9.1% to 9.1% | did not change | #8 |
exercise | no change | capillary density | lower extremity skeletal muscle of participants with PAD | - | have not shown significant effects on increased | #9 |
exercise | no change | microcirculatory delivery of oxygen and nutrients | patients with PAD | - | there are no data showing that improves | #10 |
supervised exercise | increase | plasma nitrite abundance after a treadmill walking test | people with PAD | - | effects on increased | #11 |
Walking exercise is the most effective noninvasive therapy that improves walking ability in peripheral artery disease (PAD). Biologic mechanisms by which exercise improves walking in PAD are unclear. This review summarizes evidence regarding effects of walking exercise on lower extremity skeletal muscle in PAD. In older people without PAD, aerobic exercise improves mitochondrial activity, muscle mass, capillary density, and insulin sensitivity in skeletal muscle. However, walking exercise increases lower extremity ischemia in people with PAD, and therefore, mechanisms by which this exercise improves walking may differ between people with and without PAD. Compared with people without PAD, gastrocnemius muscle in people with PAD has greater mitochondrial impairment, increased reactive oxygen species, and increased fibrosis. In multiple small trials, walking exercise therapy did not consistently improve mitochondrial activity in people with PAD. In one 12-week randomized trial of people with PAD randomized to supervised exercise or control, supervised treadmill exercise increased treadmill walking time from 9.3 to 15.1 minutes, but simultaneously increased the proportion of angular muscle fibers, consistent with muscle denervation (from 7.6% to 15.6%), while angular myofibers did not change in the control group (from 9.1% to 9.1%). These findings suggest an adaptive response to exercise in PAD that includes denervation and reinnervation, an adaptive process observed in skeletal muscle of people without PAD during aging. Small studies have not shown significant effects of exercise on increased capillary density in lower extremity skeletal muscle of participants with PAD, and there are no data showing that exercise improves microcirculatory delivery of oxygen and nutrients in patients with PAD. However, the effects of supervised exercise on increased plasma nitrite abundance after a treadmill walking test in people with PAD may be associated with improved lower extremity skeletal muscle perfusion and may contribute to improved walking performance in response to exercise in people with PAD. Randomized trials with serial, comprehensive measures of muscle biology, and physiology are needed to clarify mechanisms by which walking exercise interventions improve mobility in PAD.