Oi Keiji, Fukumoto Yoshihiro, Ito Kenta, Uwatoku Toyokazu, Abe Kohtaro, Hizume Takatoshi, Shimokawa Hiroaki
Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Tohoku J Exp Med. 2008 Feb;214(2):151-8. doi: 10.1620/tjem.214.151.
We have recently demonstrated that the low-energy extracorporeal cardiac shock wave (SW) therapy improves myocardial perfusion and cardiac function in a porcine model of chronic myocardial ischemia and also ameliorates myocardial ischemia in patients with severe coronary artery disease. The present study was designed to examine whether our SW therapy also is effective to ameliorate hindlimb ischemia in rabbits. Hindlimb ischemia was made by surgical excision of the entire unilateral rabbit femoral artery. One week after the operation, we performed the SW (n = 9) or sham-therapy (n = 9) to the ischemic region 3 times a week for 3 weeks. Three weeks after the SW therapy, the development of collateral arteries, the flow ratio of the ischemic/non-ischemic common iliac arteries, the blood pressure ratio of the ischemic/non-ischemic hindlimb, and the capillary density in the ischemic muscles were all significantly increased in the SW group compared with the control group, indicating that the SW therapy induced therapeutic angiogenesis. Importantly, no adverse effect, such as muscle damage, hemorrhage, or thrombosis, was noted with the therapy. Finally, we examined the role of endothelial nitric oxide synthesis (eNOS) and vascular endothelial growth factor (VEGF) in the mechanisms of SW-induced angiogenesis on day 28. The expression levels of eNOS and VEGF proteins in ischemic hindlimb muscles tended to be increased in the SW group compared with the control group. These results suggest that our low-energy SW therapy also is effective and safe for the treatment of peripheral artery disease.
我们最近证明，低能量体外心脏冲击波（SW）疗法可改善慢性心肌缺血猪模型的心肌灌注和心脏功能，还可改善严重冠状动脉疾病患者的心肌缺血。本研究旨在检验我们的SW疗法对改善兔后肢缺血是否也有效。通过手术切除单侧兔股动脉全程造成后肢缺血。术后1周，我们对缺血区域进行SW治疗（n = 9）或假治疗（n = 9），每周3次，共3周。SW治疗3周后，与对照组相比，SW组的侧支动脉发育、缺血/非缺血髂总动脉血流比、缺血/非缺血后肢血压比以及缺血肌肉中的毛细血管密度均显著增加，表明SW疗法诱导了治疗性血管生成。重要的是，该疗法未观察到肌肉损伤、出血或血栓形成等不良反应。最后，我们在第28天研究了内皮型一氧化氮合酶（eNOS）和血管内皮生长因子（VEGF）在SW诱导血管生成机制中的作用。与对照组相比，SW组缺血后肢肌肉中eNOS和VEGF蛋白的表达水平有升高趋势。这些结果表明，我们的低能量SW疗法治疗外周动脉疾病也是有效且安全的。
