The purpose of this study is to test the effects of leg exercise assistive paddling (LEAP) therapy during prolonged sitting (PS) on vascular and functional performance in those with peripheral artery disease (PAD) and age-matched controls. LEAP therapy is a novel application of passive limb movement to enhance blood flow through the legs without muscular contractions. Specifically, LEAP therapy is the rotational passive movement of the lower leg about the knee from 90 to 180 degrees of rotation at a cadence of 1Hz. Previous literature has indicated that this movement pattern can produce robust increases in blood flow in the passively moved limb in healthy individuals, and passive limb movement may protect vascular function during PS. However, the impact of LEAP therapy to improve blood flow in the legs of those with PAD during PS is unknown.

Participants will participate in a randomized cross-over design study with 2 visits (LEAP therapy and no LEAP therapy). For the first visit, participants will be randomly allocated to receive LEAP therapy during 2.5 hours of PS or not. For the second visit, participants will sit for 2.5 hours and will receive the condition that they did not previously receive. Before and after PS, the following measurements will be made: flow-mediated dilation of the popliteal and brachial arteries, arterial stiffness with tonometry techniques, microvascular vasodilatory capacity and skeletal muscle metabolic rate with near-infrared spectroscopy, autonomic nervous system function, and there will be blood drawn from the antecubital vein. After PS, participants will participate in a graded exercise test to assess functional walking capacity. Finally, during PS, near-infrared spectroscopy on the calf muscles and electrocardiogram will be collected continuously to monitor muscle oxygen availability and autonomic activity, respectively.

Epidemiological studies suggest that over 200 million adults worldwide currently have peripheral artery disease (PAD), which is the buildup of atherosclerotic plaques in the arteries of the legs and is associated with high rates of morbidity and mortality. The population most suspectable to PAD is older adults, with the incidence of PAD increasing exponentially after the age of 50. This sharp age demarcation makes PAD particularly concerning for Western societies, where the proportion of older adults is steadily rising, thereby making PAD a large potential future burden to healthcare systems and economies alike. Therefore, the discovery and development of interventions to prevent and treat PAD is a top biomedical concern that has a high future return on investments.

Exercise and physical activity are known to improve functional capacity in those with PAD. In fact, exercise therapies have been reported to be as effective as revascularization surgeries at restoring functional walking capacity. However, despite the major benefits of exercise, adherence to supervised exercise therapies is low, and those with PAD report being highly sedentary, which is likely attributed to the muscle pain they experience during exercise. Elevated sedentarism among those with PAD is concerning, since the investigators and others have demonstrated that sedentarism in the form of prolonged sitting (i.e., sitting for >1 hour) can 1) increase arterial stiffness, 2) reduce the vasodilatory capacities of the macro- and micro-vasculatures, 3) reduce skeletal muscle metabolism, and 4) reduce shear stress in the large conduit arteries, all of which are known to promote atherosclerosis. Importantly, since those with PAD already demonstrate impaired vascular function, they may be more suspectable to the negative effects of prolonged sitting on vascular health. Remarkably, the investigators have shown that passive movement of the legs (i.e., limb movement without active muscle contractions) can prevent vascular decline during prolonged sitting. Therefore, passive limb movement (PLM) therapies may be an effective strategy to provide light physical activity to those with PAD and protect them against the deleterious effects of sedentarism. Importantly, since PLM does not require active skeletal muscle work, it is likely that PLM will be well-tolerated by those with PAD, and adherence to PLM therapies may be enhanced compared to traditional exercise. Therefore, developing methods that mimic exercise with PLM may be an effective front-line strategy to improve functional capacity, vascular function, and quality of life in those with PAD.

Unfortunately, there are currently no available methods that provide PLM therapy for those with PAD, and it is not known whether PLM therapies can protect the vasculature of those with PAD during PS. Therefore, the investigators have developed the Leg Exercise Assistive Paddling (LEAP) protocol to provide PLM therapy during PS. LEAP therapy is a standardized protocol for those with PAD that provides PLM by rotating the lower leg about the knee from 90-180° at a cadence of 1Hz for 1 minute every 10 minutes. These parameters have been chosen for LEAP therapy because of the robust increases in leg blood flow elicited by these parameters. The investigators hypothesize that LEAP therapy prevents vascular and functional decline in those with PAD during PS. Therefore, the development and validation of LEAP therapy is expected to promote PLM therapies as a new interventional strategy to improve vascular and functional capacities in those with PAD.

Participants will participate in a randomized cross-over design study with 2 visits (LEAP therapy and no LEAP therapy). For the first visit, participants will be randomly allocated to receive LEAP therapy during 2.5 hours of PS or not. For the second visit, participants will sit for 2.5 hours and will receive the condition that they did not previously receive. Before and after PS, the following measurements will be made: flow-mediated dilation of the popliteal and brachial arteries, arterial stiffness with tonometry techniques, microvascular vasodilatory capacity and skeletal muscle metabolic rate with near-infrared spectroscopy, autonomic nervous system function, and there will be blood drawn from the antecubital vein. After PS, participants will participate in a graded exercise test to assess functional walking capacity. Finally, during PS, near-infrared spectroscopy on the calf muscles and electrocardiogram will be collected continuously to monitor muscle oxygen availability and autonomic activity, respectively.

Inclusion Criteria:

PAD subjects:

• Able to provide written informed consent
• 50-85 years of age
• Diagnosed with Peripheral Arterial Disease (PAD) Fontaine stage II-III
• Women must be postmenopausal (cessation of menses for > 24 months)
• History of exercise-induced claudication
• Free of ulcers, gangrene, or necrosis of the foot, Fontaine stage IV PAD

Age-matched control subjects:

• Able to provide written informed consent
• 50-85 years of age
• No evidence of peripheral occlusive disease, ankle-brachial index > 0.90
• Women must be postmenopausal (cessation of menses for > 24 months)

Exclusion Criteria:

PAD subjects:

• Pain at rest and/or tissue loss from Peripheral Arterial Disease (PAD), Fontaine stage IV PAD
• Acute lower extremity ischemic event secondary to thromboembolic disease or acute trauma
• Limited walking capacity from conditions other than PAD
• Have not had a physical exam to assess exercise limitations in the past year
• Pregnant or nursing
• Kidney disease or type II diabetes mellitus

Age-matched control subjects:

• Positive diagnosis of Peripheral Arterial Disease (PAD)
• Any exercise limitations as determined at last physical exam, at least 1 year prior to study
• Have not had a physical exam to assess exercise limitations in the past year
• Limited walking capacity from musculoskeletal injury
• Pregnant or nursing
• Kidney disease or type II diabetes mellitus

There is no plan to share individual participant data with other researchers.