Abstract 18084: Diabetes Promotes Tissue Nitric Oxide (NO) Insufficiency in Critical Limb Ischemia Patients
Background: Diabetic patients are 5 times more likely than non-diabetics to develop critical limb ischemia (CLI). The pathogenesis of CLI in diabetic patients remains poorly understood and at present there is a paucity of effective therapies to treat this devastating disease. Nitrite (NO2) and nitrosothiols (RSNO) have recently emerged as important storage forms of nitric oxide (NO) that modulate vascular reactivity and signaling. The purpose of this study was to investigate tissue NO bioavailability in muscle biopsies obtained from non-diabetic and diabetic (Db) patients following leg amputation.
Methods: Gastrocnemius and tibialis anterior tissue was attained post-amputation from human non-diabetic patients with CLI (n=12) and diabetic patients with CLI (n=8). Nitrite concentrations were determined by ion chromatography methods. RSNO and NO-Heme levels were measured by chemiluminescence detection.
Results: The CLI + Db group displayed reduced skeletal muscle (89.9 vs. 55.5 nM, p < 0.05) nitrite levels compared to the CLI group without Db. Nitrosothiol (21.2 vs. 10.52 nM, p < 0.05) concentrations and NO-Heme (27.61 vs. 13.0 nM, p < 0.05) levels were also significantly attenuated in the CLI + Db group.
Conclusion: These data clearly indicate significant reductions in NO bioavailability (nitrite, RSNO, and NO-heme) in diabetics with CLI. Future studies will evaluate the cellular mechanisms responsible for reduced NO levels in diabetic patients with CLI. Nitric oxide based therapeutics including sodium nitrite may be suitable to treat diabetic patients with CLI to attenuate the progression of this disease.
- © 2013 by American Heart Association, Inc.