Abstract 538: Local Hydrogen Sulfide Therapy Augments Angiogenesis And Ischemic Wound Healing

Abstract

Introduction: Hydrogen sulfide (H 2 S) is an important signaling molecule in cellular O 2 sensing, wound healing and angiogenesis. Low H 2 S levels have been shown in diabetes and cardiovascular disease and H 2 S impairment may play a role in chronic non-healing ischemic wounds. H 2 S promotes angiogenesis in cell culture but in vivo data are lacking. We utilized a novel local H 2 S delivery method to investigate the effects of H 2 S therapy in rodents. Methods: Sprague Dawley rats (n=6-10/group) underwent dorsal myocutaneous ischemic flap wound creation under anesthesia. NaHS solution (100 μM) was delivered locally to the wound every 12 hours via implanted microtubing externalized and attached to a fluid delivery vest. Sham rats received saline solution while a third group received H 2 S blocker DL-propargylglycine (PAG). Laser speckle contrast images (LSCI) were recorded over 14 days. Flap tissue was collected for histologic analysis of tissue viability and degree of ischemic insult. Neovascularization was quantified by CD31 immunohistochemistry (IHC). VEGF protein expression was quantified by Western blot. Results: H 2 S treated flaps reperfused at a two-fold greater rate compared to sham and PAG treated flaps by LSCI (mean 12.9 flux/day vs. 6.9 flux/day, P=0.02). IHC mean microvascularity in sham flaps was 18 vessels/mm 2 compared to 47 vessels/mm 2 in H 2 S treated flaps (P=0.0092). Panniculus carnosis muscle thickness (408 μm vs. 234 μm) and myofibril count (56 vs. 38/100k μm 2 ) were preserved in H 2 S treated flaps (P=0.02, 0.04). H 2 S treatment upregulated VEGF while PAG was associated with decreased expression. Conclusion: H 2 S treated flaps have improved wound revascularization, tissue healing and angiogenic signaling. Blockade of H 2 S results in poor revascularization and decreased angiogenic protein expression. H 2 S pathways may play a critical role in the pathogenesis of impaired wound healing and could represent a potential therapeutic target for ischemic wounds.