Extracorporeal Shock Wave Therapy Ameliorates Hindlimb Ischemia in Rabbits

Abstract

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 fl ow 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 signifi cantly 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.shock wave therapy; angiogenesis; peripheral artery disease; blood fl ow; capillary density. Tohoku J. Exp. Med., 2008, 214 (2), 151-158.

Microvascular Response to Shock Wave Application in Striated Skin Muscle

“…In our study, eNOS was significantly up-regulated 1 d after ESWA. The observation of increased eNOS levels after ESWA is in line with findings of other researchers [41][42][43]. In addition, we observed a significantly increased expression of vWF within the endothelial lining.…”

Extracorporeal Shock Wave Therapy as a New and Non-invasive Angiogenic Strategy

“…The development of collateral arteries was enhanced in the SW-treated rabbit compared with the control animals. Quoted from Oi et al 2008 with permission.…”

“…Therefore, we aimed to apply our cardiac SW therapy to PAD. We studied the effects of our SW therapy on hindlimb ischemia in rabbits (Oi et al 2008). Hindlimb ischemia was induced by surgical excision of the entire unilateral femoral artery.…”

“…Furthermore, the lithotripsy therapy with highenergy SW is indicated for gallstones, pancreatic and salivary stones. We have recently developed a new, noninvasive angiogenic therapy using low-energy shock waves (SW) which level is approximately 10% of that used for urinary lithotripsy treatment (Nishida et al 2004;Fukumoto et al 2006;Uwatoku et al 2007;Oi et al 2008;Shimokawa and Ito 2009). Based on our reports in animals and humans (Nishida et al 2004;Fukumoto et al 2006), Aicher et al employed a low-energy SW therapy to treat hindlimb ischemia in rats in combination with cell-based therapy (Aicher et al 2006).…”

Shock wave treatment enhances endothelial proliferation via autocrine vascular endothelial growth factor

“…ESWT has been shown to promote coronary angiogenesis in the ischemic myocardium and improve myocardial function in vivo in a porcine model of chronic myocardial ischemia (Nishida et al, 2004). Meanwhile, ESWT has also been effective in the promotion of angiogenesis in a rabbit model of hindlimb ischemia (Oi et al, 2008). The precise mechanism underlying ESWT-induced angiogenesis remains unknown.…”