Abstract 9481: Whole Body Periodic Acceleration, Novel Passive Exercise Devices, Enhances Blood Supply to Ischemic Hindlimb in Mice and Human

Introduction: Whole body periodic acceleration (WBPA) is a non-invasive, passive exercise device that has been shown to improve endothelial function by increasing shear stress by head-to-foot direction movements of the body. However, the impact of WBPA on blood flow to ischemic legs has not been investigated. Hypothesis: WBPA enhances blood supply in a mouse model of hindlimb ischemia and in patients with peripheral arterial disease (PAD). Methods and Results: After unilateral femoral artery excision, wild type mice were assigned to either the WBPA (n=15) or control (n=13) group. WBPA was applied at 150 cpm for 45 min under anesthesia once a day. WBPA significantly increased blood flow recovery at 7 and 14 days after 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-treated mice compared with control mice, suggesting that WBPA promotes angiogenesis at a microcirculatory level. WBPA increased the phosphorylation of endothelial nitric oxide synthase (eNOS) in adductor muscle. The pro-angiogenic 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 PCR analysis showed significant increases in molecules involved in angiogenesis, such as VEGF, FGF2, SDF-1, PDGF-B in ischemic hindlimb by WBPA. Protein array analysis showed that WBPA induced changes in the expression profile of serum angiogenesis-related proteins. Facilitated blood flow recovery was observed in a mouse model of diabetes despite no changes in glycemic control. Clinically, 10 patients (age, 69±7 years, 9 men) with PAD underwent single session of WBPA treatment at 140 cpm for 45 min. WBPA significantly improved the ischemic/non-ischemic ratio of blood flow in the lower extremity from 0.74±0.21 to 0.87±0.21 (p<0.05). Conclusions: WBPA increased blood supply to ischemic lower extremities through activation of eNOS signaling and upregulation of pro-angiogenic growth factor in ischemic skeletal muscle. WBPA is a potentially suitable non-invasive intervention to facilitate therapeutic angiogenesis.