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.