Abstract 15790: An Evolving Approach of Therapeutic Angiogenesis with Sodium Sulfide in Critical Limb Ischemia of Type 2 Diabetic and Eldely Mouse Hind Limb
Introduction:Patients with type 2 diabetes mellitus (DM) frequently have peripheral arterial disease, with a predilection for the lower legs. Diabetes is one of the negative predictors of therapeutic angiogenesis. Hydrogen sulfide (H2S) is a gaseous signaling molecule which has endothelial cell proliferation, anti-apoptosis, anti -inflammatory, vasodilatation and anti-oxidant effects. The effect of sodium sulfide (prodrug of H2S) in diabetic ischemic angiogenesis is yet to be reported.
Hypothesis: Sodium sulfide therapy augments blood perfusion by stimulation of ischemic angiogenesis in type 2 diabetic mouse critical limb ischemia
Methods: Hind limb ischemia was induced in 42 weeks old DB/DB type 2 DM mice by ligating and excising the left femoral vessels. Mice were randomly assigned to two experimental groups (n=8, each group); PBS (Control) or 0.5 mg/kg sodium sulfide. Sodium sulfide was administered twice daily by retro-orbital injection starting at day 5 and continued until day21. Body weight, Blood glucose and lipid panel were investigated before and after study period. Blood perfusion was measured by laser Doppler perfusion image system. Angiogenic index and proliferation index were measured by the ratio of CD31 positive / DAPI positive vessels and Ki67 positive / DAPI positive vessels respectively. Capillary myo-fiber ratio was determined by Nova red staining. Apoptosis assay was determined by tunnel assay
Results: Sodium sulfide therapy did not significantly alter blood glucose, body weight or lipid panels compared to control PBS therapy. Blood perfusion, angiogenic index and cell proliferation index were significantly increased in the sodium sulfide therapy group compared to the PBS control group.
Conclusions: Sodium sulfide therapy completely restored blood flow in type 2 diabetic ischemic limbs by increasing angiogenic activity and decreasing apoptosis. Sodium sulfide therapy may be beneficial for PAD in non-insulin dependent diabetes.
- © 2010 by American Heart Association, Inc.