Near-Infrared Spectroscopy-Guided Exercise Training in Peripheral Arterial Disease

Background: Patients suffering with atherosclerotic peripheral arterial disease (PAD) have limited therapeutic options to improve claudication. Supervised exercise programs are generally effective in improving leg pain from walking, but are poorly adhered to because of patient discomfort. The benefit of exercise training programs is thought to be mediated in part through repeated ischemic stimuli that activate endogenous regenerative mechanisms. In preliminary studies, exercise-induced tissue desaturation by near infrared spectroscopy (NIRS) precedes the onset of leg pain. This proposal aims to explore a novel strategy of exercise training in PAD based on measured tissue hypoxia rather than pain symptoms using NIRS to non-invasively characterize muscle oxygen tension.

Methods: In subjects with symptomatic peripheral arterial disease, the efficacy of a novel NIRS-based strategy of thrice-weekly exercise training will be assessed. Enrolled subjects will be randomized to NIRS-based training, traditional claudication-based training, or self-directed walking. The hypotheses tested include: 1) NIRS-directed exercise improves claudication to a similar degree as symptom-directed exercise training and 2) is superior to self-directed walking. In the symptom-based group, physical effort will be dictated by claudication symptoms, whereas in the hypoxia-based training program, physical effort is dictated by NIRS measure of calf oxygen tension. Efficacy in the training programs will be evaluated by total walking time on a standard graded treadmill test after 12 weeks. Other measures will be claudication onset time, subjective and objective measures of physical activity, changes in vascular function. In addition, the hypothesis that hypoxia-directed training will result in increased ischemic signaling and increased progenitor cell mobilization to a degree similar as in claudication-based training will be tested.

Conclusions: These experiments will test whether a training strategy based on tissue hypoxia (measured by NIRS) is as effective as and more tolerable than traditional symptom-based training programs in PAD. In addition, these experiments will characterize mechanistic responses to hypoxia that may account for clinical improvements that exercise training affords.