Abstract 21068: Far Red/Near Infrared Light Stimulates Hindlimb Collateralization via Nitric Oxide
Peripheral artery disease (PAD) has significant morbidity due to amputation associated from the development of critical limb ischemia. Present therapies are non-curative, however developing a functional collateral circulation in the lower extremities could offer a new therapeutic modality. We hypothesized application of light in the far red/near infrared region (670nm; NIR), which stimulates wound healing, growth factor release and enzyme activation, would enhance collateral development in an ischemic limb.
Methods: Femoral artery ligation and excision were performed in NZW rabbits. After 14 days, collateral vessels were counted. NIR (20J) was applied daily for 10 min to the femoral surgical site for 14 days. Ischemia alone stimulated collateral development compared to the non-ischemic limb (11 vessels vs. 6, p<0.05). NIR applied to the ischemic limb stimulated collateralization (16 vessels vs. 11, p<0.05). Interestingly, NIR treatment of the ischemic limb in the presence of the nitric oxide synthase (NOS) inhibitor L-NAME did not attenuate vessel formation. However, infusion of carboxy-PTIO, a NO scavenger (0.17 mg/kg/min) during application of NIR markedly reduced collateral development (9 vessels vs. 16; p<0.05). In vitro, NIR stimulated coronary vascular smooth muscle cell (SMC) proliferation 50% and endothelial cell proliferation by 70%. NIR (4J a day for 4 days) also stimulated endothelial cell tube formation, which was inhibited by carboxy-PTIO (100 uM) but not by L-NAME (1 mM). To further elucidate and identify NO related genes affected by NIR, gene expression arrays using RT-PCR were performed in SMC. Genes involved in the production of reactive oxygen species (myeloperoxidase and eosinphil peroxidase genes) were downregulated 30 min after exposure to NIR. These results suggest NIR can increase NO bioavailability in vivo independent of NOS activation and downregulation of genes responsible for formation of reactive oxygen species. NO is required for in vivo and in vitro collateralization/tube formation by NIR. These results suggest that NIR may provide a noninvasive therapy for alleviating ischemia in PAD.
- © 2010 by American Heart Association, Inc.