Abstract 288: Impaired Ischemic Myocutaneous Wound Revascularization And Transdermal H 2 S Emissions In Diabetic Rats

Abstract

Introduction: Hydrogen sulfide (H 2 S) has been recognized as an important signaling molecule in cellular O 2 sensing, wound healing and angiogenesis. Studies have shown abnormal H 2 S levels in diabetic patients with cardiovascular disease. Diminished H 2 S signaling may play a causative role in diabetic foot wounds. The Transdermal Arterial Gasotransmitter Sensor (TAGS) device measures real-time H 2 S emissions through the skin. In this work, we utilize the novel TAGS device to characterize transdermal H 2 S emissions during diabetic and non-diabetic wound healing for the first time. Methods: Dorsal peninsular-shaped myocutaneous ischemic flap wounds were created under anesthesia. Sprague Dawley (SD) and Zucker Diabetic Fatty (ZDF) rats (n=10 each) were compared. Transdermal H 2 S emissions, laser speckle contrast images (LSCI) and planimetric photos were serially taken from the wound flap area over 14 days. After animal sacrifice, healed flap tissue was collected for histologic (H&E) analysis of panniculus carnosus (skin muscle) viability as a proxy for degree of ischemic insult. Results: ZDF rats were significantly hyperglycemic (mean 516 mg/dL vs. 201 mg/dL for SD, P=0.002). Similar mean baseline (preoperative) H 2 S emissions were observed in SD (16 ppb) and ZDF (12 ppb) rats (P=0.25). During revascularization and healing, ZDF wounds emitted significantly less H 2 S (10 ppb at day 14) as compared to SD (28 ppb at day 14, P<0.01). ZDF wounds demonstrated impaired flap engraftment and revascularization by LSCI (mean 65.6 Perfusion Units (PU) for ZDF vs. 188.0 PU for SD at day 14, p<0.01) and planimetric analysis (mean 16.6% necrosis for ZDF vs. 5.3% necrosis for SD at day 14, p=0.01). Panniculus carnosus mean myofibril count, myofibril diameter, and layer thickness were significantly decreased (p<0.01) in the ZDF cohort, suggesting greater tissue ischemic insult and muscle loss. Conclusion: Diabetic rats have impaired wound H 2 S production and poor revascularization. These physiologic alterations are accompanied by greater wound necrosis and histologic ischemic insult. This suggests H 2 S abnormalities in diabetes may play a role in the pathogenesis of impaired wound healing and could represent a potential future therapeutic target for these difficult wounds.