. Terjung. Time course of changes in collateral blood flow and isolated vessel size and gene expression after femoral artery occlusion in rats.

Exercise produces a powerful angiogenic stimulus within the active muscle that leads to a functionally important increase in capillarity. Further, exercise can increase flow capacity by enlarging the caliber of arterial supply vessels. These adaptations are achieved by the processes of angiogenesis and arteriogenesis, respectively.

Peripheral arterial disease (PAD) is a common vascular disease that reduces blood flow capacity to the legs of patients. PAD leads to exercise intolerance that can progress in severity to greatly limit mobility, and in advanced cases leads to frank ischemia with pain at rest. It is estimated that 12–15 million people in the United States are diagnosed with PAD, with a much larger population that is undiagnosed. The presence of PAD predicts a 50–1500% increase in morbidity and mortality, depending on severity. Treatment of patients with PAD is limited to modification of cardiovascular disease risk factors, pharmacological intervention, surgery, and exercise therapy. Extended exercise programs that involve walking ~5 times/wk, at a significant intensity that requires frequent rest periods, are most significant. Pre-clinical studies and virtually all clinical trials demonstrate the benefits of exercise therapy, including: improved walking tolerance, modified inflammatory/hemostatic markers, enhanced vasoresponsiveness, adaptations within the limb (angiogenesis, arteriogenesis, mitochondrial synthesis) that enhance oxygen delivery and metabolic responses, potentially delayed progression of the disease, enhanced quality of life indices, and extended longevity. A synthesis is provided as to how these adaptations can develop in the context of our current state of knowledge and events known to be orchestrated by exercise. The benefits are so compelling that exercise prescription should be an essential option presented to patients with PAD in the absence of contraindications. Obviously, selecting for a life style pattern, that includes enhanced physical activity prior to the advance of PAD limitations, is the most desirable and beneficial.

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