Extracorporeal Shock Wave Therapy Ameliorates Hindlimb Ischemia in Rabbits

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.