Title: How does exercise improve the calf muscle in patients with poor blood supply to their leg?

Purpose of the project: Patients with peripheral arterial disease have a poor blood supply to their lower leg. The reduced inflow prevents the leg from utilising nutrients and oxygen as easily as a healthy leg would. This causes pain when walking (intermittent claudication), which often occurs after a reproducible distance e.g. every 50 yards. These patients have a reduction in their quality of life as they feel embarrassed in social situations e.g. walking around town requires multiple breaks, so they tend to avoid this and isolate themselves more.

One treatment for claudication is exercising until the pain comes on; which most are reluctant to do. Walking up to three times a week for an hour, can double most people's walking distances, but doesn't always. The reason why some improve with exercise and others do not remains unknown.

This project will be the first randomised controlled trial of exercise in claudicants that focuses on the adaptations that occur in the muscle at a cellular level. We wish to compare muscle cells from a group that have exercised and group that have not. We will focus on the change in muscle cell size and function at present, and later progress to why and how this happens.

Methods: We will take measurements at the start of the study (baseline), after 6 weeks and then 3, 6 and 12 months. These measurements will be of a patient's fitness, actual walking distances and blood samples. At the time of surgery, muscle from the calf will be taken from the affected leg. This will be processed at the University's biomedical science department to look at the different types of muscle fibre and how efficiently they are working.

Inclusion Criteria:

• Community dwelling older adults aged 45 and over
• Diagnosis of intermittent claudication - ABPI < 0.9 with symptoms in keeping with intermittent claudication
• Undergoing surgery for claudication
• Ability to walk without assistance
• Healthy control patients who are undergoing varicose vein surgery

Exclusion Criteria:

• Participants who are unable to provide informed consent
• Severe of acute cardiovascular, musculoskeletal or pulmonary illness
• Critical limb ischaemia
• Active treatment for cancer
• Rheumatoid arthritis or any patient receiving steroids or disease modifying Antirheumatic drugs (DMARDS)
• Failure to complete a CPET