Therapeutic vascular angiogenesis for intractable macroangiopathy-related digital ulcer in patients with systemic sclerosis: a pilot study.

OBJECTIVE: SSc causes intractable ischaemic ulcers. To avoid major amputation, we examined the safety and efficacy of therapeutic vascular angiogenesis for digital ulcers due to SSc. METHODS: A single-centre, open-label pilot study was conducted in patients with an ischaemic digital ulcer [n = 40, mean age 65 years (s.d. 8), Rutherford class III-5 or III-6) due to lcSSc (n = 11) or arteriosclerosis obliterans (ASO; n = 29). Bone marrow mononuclear cells (0.4-5.1 × 10(10) cells in total) were administered into the ischaemic limbs. We evaluated short-term safety and efficacy by means of a pain scale, (99m)Tc-tetrofosmin scintigraphy and transcutaneous oxygen tension (TcPO2) before and 4 weeks after treatment. Also, the 2-year outcome was compared. RESULTS: There was a case of amputation in each group within 4 weeks after therapy. The pain scale significantly decreased in both groups [lcSSc 93 mm (s.d. 9) to 11 (s.d. 16), P < 0.01; ASO 77 mm (s.d. 22) to 16 (s.d. 13), P < 0.01] and TcPO2 significantly improved [lcSSc 9.0 mmHg (s.d. 9) to 35 (s.d. 14), P < 0.01; ASO 18 mmHg (s.d. 10) to 29 (s.d. 21), P < 0.05). At the 2-year follow-up, the limb amputation rate was 9.1% in lcSSc and 20.7% in ASO (P = 0.36), while the recurrence rate was 18.2% in lcSSc and 17.2% in ASO (P = 0.95). All-cause mortality was 27.3% in lcSSc and 17.2% in ASO (P = 0.65). CONCLUSION: In patients with lcSSc, bone marrow mononuclear cell implantation provides clinical benefit and is safe, without major adverse reactions, and may become an effective strategy. TRIAL REGISTRATION: UMIN-CTR, http://www.umin.ac.jp/ctr/index-j.htm, no. UMIN000004112.

Low-energy extracorporeal shock wave therapy improves microcirculation blood flow of ischemic limbs in patients with peripheral arterial disease: pilot study.

BACKGROUND: Because direct application of low-energy shock waves induces angiogenesis, we investigated the safety and efficacy of this new therapy to develop a noninvasive method of repeatable therapeutic angiogenesis for treating peripheral arterial disease (PAD). SUBJECTS AND METHODS: The subjects were 10 patients who had symptomatic PAD and limited ischemia in a below-the-knee artery. Low-energy shock waves were directly applied to the calf muscles 6 times every other day. Intracorporeal changes were evaluated with ultrasonography to determine adverse effects of therapy. To assess blood flow of the microcirculation, transcutaneous oxygen tension (TcPO2), skin perfusion pressure (SPP), and (99m)technetium-tetrofosmin ((99m)Tc-TF) scintigraphy were performed before and after therapy. The TcPO2 was measured while subjects inhaled pure oxygen (maximum TcPO2). The (99m)Tc-TF perfusion index was determined as a ratio of uptake in muscle to that in the brain (control) for quantitative analysis. RESULTS: No adverse effects were noted in any patient. Maximum TcPO2 values increased significantly on the calf (57.3±28.4 to 71.0±14.5 mm Hg, p=0.044) and the dorsum of the foot (52.2±21.8 to 76.1±17.9 mm Hg, p=0.012). The SPP tended to increase after therapy on the dorsum and plantar surfaces of the foot, but the differences were not significant. The (99m)Tc-TF perfusion index in the foot significantly increased (0.48±0.09 to 0.61±0.12, p=0.0013), but that in the leg did not change. CONCLUSION: We have demonstrated that low-energy shock wave therapy is safe and can restore blood flow in the microcirculation in patients with symptomatic PAD.