Establishment of optimal exercise therapy using near-infrared spectroscopy monitoring of tissue muscle oxygenation after therapeutic angiogenesis for patients with critical limb ischemia: A multicenter, randomized, controlled trial.

Critical limb ischemia (CLI) is a potentially life-threatening condition that involves severely reduced blood flow to the peripheral arteries due to arteriosclerosis obliterans (ASO) of the limbs or a similar condition. CLI patients must undergo revascularization to avoid amputation of the lower limbs and improve their survival prognosis. However, the outcomes of conventional surgical revascularization or endovascular therapy are inadequate; therefore, establishing further effective treatment methods is an urgent task. We perform therapeutic angiogenesis using autologous bone marrow-derived mononuclear cells in clinical practice and demonstrated its safety and efficacy for CLI patients for whom conventional treatments failed or are not indicated. Exercise therapies must be devised for CLI patients who have undergone therapeutic angiogenesis to save their limbs and improve survival. Because evidence regarding the efficacy and safety of exercise therapy for CLI patients is lacking, we plan to perform a prospective trial of the efficacy and safety of optimal exercise therapy following therapeutic angiogenesis for CLI patients.The trial will enroll 30 patients between 20 and 79 years with Rutherford category 4 or 5 CLI caused by ASO who will undergo therapeutic angiogenesis. Participants will be randomly allocated to receive either optimal exercise therapy or fixed exercise therapy. Those receiving optimal exercise therapy will undergo tissue muscle oxygen saturation monitoring using near-infrared spectroscopy while performing exercises and will be prescribed optimal exercise therapy. The optimal amount of exercise will be determined on day 8, 31, 61, 91 and 181 after therapeutic angiogenesis. ETHICS AND DISSEMINATION: This protocol was approved by the Institutional Review Boards of Kyoto Prefectural University of Medicine. In accordance with the Helsinki Declaration, written informed consent has been obtained from all participants prior to enrollment. The results of this trial will be disseminated by publication in a peer-reviewed journal. TRIAL REGISTRATION: This trial is registered at http://www.umin.ac.jp/ctr/index.htm (identifier: UMIN000035288).

Effects of electrical stimulation therapy on the blood flow in chronic critical limb ischemia patients following regenerative therapy.

OBJECTIVES: We investigated the effects of electrical stimulation therapy on cutaneous and muscle blood flow in critical limb ischemia patients following regenerative therapy. METHODS: Three groups were studied: 10 healthy young subjects, 10 elderly subjects, and 7 critical limb ischemia patients after regenerative therapy. After 5 min rest, electrical stimulation was applied at 5 Hz on the tibialis anterior muscle for 10 min. We estimated the relative changes in oxyhemoglobin and total hemoglobin compared to the basal values at rest (Δ[HbO2], Δ[Hbtot]), which reflected the blood flow in the skin and muscle layer, and we simultaneously measured the tissue O2 saturation (StO2) throughout the electrical stimulation and recovery phase by near-infrared spectroscopy. RESULTS: The Δ[HbO2] and Δ[Hbtot] values of the muscle layer in critical limb ischemia patients increased gradually and remained significantly higher at the 5-min and 10-min recovery periods after the electrical stimulation without reducing the StO2, but there is no significant change in the other two groups. Skin blood flow was not influenced by electrical stimulation in three groups. CONCLUSION: This improvement of the peripheral circulation by electrical stimulation would be beneficial as the adjunctive therapy after regenerative cell therapy.