Impaired Diabetic Myocutaneous Wound Revascularization Is Associated With Reduced Transdermal H(2)S.

INTRODUCTION: As the prevalence of diabetes mellitus continues to rise, morbidity associated with nonhealing diabetic wounds is becoming more common. Hydrogen sulfide (H(2)S) has been increasingly recognized as an important signaling molecule in wound healing and angiogenesis. Obesity and diabetes are associated with decreased levels of circulating and transdermal H(2)S, but skin H(2)S emissions during wound healing have not previously been established. This study aims to describe H(2)S physiology during diabetic ischemic wound healing and revascularization. MATERIALS AND METHODS: Sprague Dawley and Zucker diabetic fatty (ZDF) rats underwent creation of full-thickness ischemic myocutaneous flap wounds. Revascularization was followed for 14 days by serial laser speckle contrast imaging and transdermal H(2)S emissions during healing. The degree of ischemic tissue injury (panniculus carnosus thickness) and neovascularization (CD31 immunohistochemistry) were assessed histologically. Vascular endothelial growth factor was measured by Western immunoblot. RESULTS: ZDF rats were observed to have impaired skin perfusion at baseline and during flap engraftment [64 perfusion units (PU) versus 184 PU, P < 0.01], which mirrored deficits in H(2)S emissions of the healing flap wound (10 parts per billion [ppb] versus 28 ppb, P < 0.01). Significantly worse tissue ischemic injury and neovascularization were noted in ZDF animals compared to Sprague Dawley (12 CD31(+) vessels/mm(2) versus 20, P = 0.02), which correlated with a two-fold deficit in vascular endothelial growth factor expression compared to nondiabetic animals. CONCLUSIONS: Impairments in transdermal H(2)S emissions are present in diabetic ischemic wounds and are associated with deficits in wound revascularization, perfusion, maintenance of tissue architecture, neovascularization, and angiogenic signaling. H(2)S therapies may be a viable novel option for this challenging clinical problem.