Abstract
Chronic limb-threatening ischemia (CLTI) is a major public health problem. Low-intensity pulsed ultrasound (LIPUS) has been shown to improve ischemic limb conditions in patients with CLTI. However, the possible mechanisms of these benefits require further understanding. A total of 37 atherosclerotic peripheral artery disease patients with CLTI (Fontaine class III or IV) who were not suitable for standard revascularization therapies were enrolled. Patients were treated with LIPUS daily for 20 min. Clinical parameters were evaluated at baseline and after 4 weeks and 12 weeks of treatment with LIPUS. Rest pain intensity on a visual analog scale (P = 0.018), walking impairment questionnaire score (P < 0.001), skin perfusion pressure (P < 0.001), flow-mediated vasodilation (P < 0.001), nitroglycerine-induced vasodilation (P = 0.002), white blood cell count (P = 0.013), ALT (P = 0.001), AST (P = 0.017), and high-sensitivity C-reactive protein (P = 0.011) were significantly improved after LIPUS treatment. None of the patients withdrew from the study due to adverse effects associated with LIPUS. During a mean follow-up period of 91.4 ± 49.0 months, the rate of survival was 88.9% at 1 year and the rate of limb survival was 88.6% at 1 year. LIPUS exposure may have favorable effects on clinical symptoms, inflammation, perfusion parameters, and vascular function in patients with CLTI and it can be used safely.Clinical Trial Registration Information: URL for Clinical Trial: https://www.umin.ac.jp/ctr/index.htm ; Registration Number for Clinical Trial: UMIN000004901, UMIN000014757; https://jrct.niph.go.jp/search ; Registration Number for Clinical Trial: jRCTs062200008.