051 Topical Oxygen Alters Angiogenesis-Related Growth Factor Expression in Chronic Diabetic Foot Ulcers

Abstract

Objective: Following tissue vascular and oxygen delivery disruption, normal wound healing is a complex process requiring restoration of supplies of oxygen and other nutrients through blood vessel regeneration, or angiogenesis. Angiogenesis is stimulated by synergistic interactions of growth factors and cytokines secreted by damaged cells in wound tissues exhibiting hypoxia, high lactate levels, and inflammation. Chronic wounds, often complications of diabetes, are characterized by chronic hypoxia, inflammation, and insufficient growth factor secretion. To test growth factor sensitivity to reversed hypoxia in chronic human wounds, we administered pure oxygen topically to chronic foot ulcers in diabetic humans and used molecular probes to measure growth factors previously found to regulate angiogenesis and improve delayed healing, i.e., VEGF et al. Methods: By multiplex ELISA assays of growth factor cytokines, we quantified pg/ug levels of total proteins detectable in fluids collected from human diabetic plantar wounds after exposure to topical oxygen delivered in 0–50 mm Hg pulses during 90-minute treatments 4 days per week over a 5 week protocol. Wounds that had failed to heal for at least 4 weeks were infused with a maximum of 1.06 ATM of oxygen at 1 minute intervals in a lower limb enclosing chamber. Findings: Our initial data show increased expression in angiogenesis-related growth factors (bFGF, HB-EGF, HGF, KGF, VEGF) in wound fluid from chronic diabetic foot ulcers using the Topical Hyperbaric Oxygen Chamber (Advanced Hyperbaric Technologies, Inc., Farmingdale, NJ). Secretion of the most crucial angiogenic factor, VEGF, was increased by 8-fold to well over 10-fold using the described protocol. Conclusions: These data show evidence of a molecular mechanism for the scientific basis of topical hyperbaric oxygen-modulated growth factor expression in chronic diabetic wounds, previously unresponsive to standard wound care. We conclude that topically applied hyperbaric oxygen alters angiogenesis-related growth factor expression in wound fluids from chronic diabetic foot ulcers in a manner consistent with renewed healing. Acknowledgments: Advanced Hyperbaric Technologies, Inc., Farmingdale, NJ.