Impairment of microcirculation and energy metabolism in intermittent claudication: beneficial effects of exercise training

Although in peripheral arterial disease (PAD) the primary determinant of inadequate blood supply to the affected limb during exercise is a flow-limiting lesion of a conduit artery, there is a large body of evidence that impairment of microcirculation and skeletal muscle energy metabolism play a relevant role in the reduced working ability of affected individuals. This review was conceived to cast some light on this topic, paying special attention to the functional benefits of exercise training (ET) in the treatment of claudicant patients. In PAD, the ischemia induced by maximal exercise increases oxidative stress, inflammation and endothelial dysfunction. Perturbation of the endothelial homeostasis results in increased adhesiveness of leukocytes and platelets, and in reduced vasodilator capability. These events, expression of the interplay between inflammation and endothelium, provoke an obstacle in the microcirculation with a reduction in the nutritive blood flow, leading to acidosis and impaired energy metabolism in skeletal muscle, with consequent reduced exercise tolerance. ET counteracts these effects by improving walking ability and quality of life in patients with intermittent claudication, thus representing the gold standard in the treatment of PAD.