Passive exercise using whole-body periodic acceleration enhances blood supply to ischemic hindlimb.

OBJECTIVE: Whole-body periodic acceleration (WBPA) has been developed as a passive exercise technique to improve endothelial function by increasing shear stress through repetitive movements in spinal axis direction. We investigated the effects of WBPA on blood flow recovery in a mouse model of hindlimb ischemia and in patients with peripheral arterial disease.

METHODS AND RESULTS: After unilateral femoral artery excision, mice were assigned to either the WBPA (n=15) or the control (n=13) group. WBPA was applied at 150 cpm for 45 minutes under anesthesia once a day. WBPA significantly increased blood flow recovery after ischemic surgery, as determined by laser Doppler perfusion imaging. Sections of ischemic adductor muscle stained with anti-CD31 antibody showed a significant increase in capillary density in WBPA mice compared with control mice. WBPA increased the phosphorylation of endothelial nitric oxide synthase (eNOS) in skeletal muscle. The proangiogenic effect of WBPA on ischemic limb was blunted in eNOS-deficient mice, suggesting that the stimulatory effects of WBPA on revascularization are eNOS dependent. Quantitative real-time polymerase chain reaction analysis showed significant increases in angiogenic growth factor expression in ischemic hindlimb by WBPA. Facilitated blood flow recovery was observed in a mouse model of diabetes despite there being no changes in glucose tolerance and insulin sensitivity. Furthermore, both a single session and 7-day repeated sessions of WBPA significantly improved blood flow in the lower extremity of patients with peripheral arterial disease.

CONCLUSIONS: WBPA increased blood supply to ischemic lower extremities through activation of eNOS signaling and upregulation of proangiogenic growth factor in ischemic skeletal muscle. WBPA is a potentially suitable noninvasive intervention to facilitate therapeutic angiogenesis.