Abstract 19162: A Novel Hydrogen Sulfide Prodrug, SG-1002, Augments Angiogenesis in a Swine Model of Critical Limb Ischemia
Introduction: Despite advances in revascularization, treatments for critical limb ischemia (CLI) have been largely unsuccessful. Hydrogen sulfide (H2S), a gaseous signaling molecule, exerts potent vasodilatory and proangiogenic effects. We sought to determine whether a novel H2S prodrug, SG-1002, promotes peripheral revascularization.
Methods: CLI was generated in Yucatan miniswine (n=17) by placement of an Amplatzer vascular plug deployed within a Viabahn stent in the proximal external iliac artery. At day 7 post-CLI pigs received daily placebo or SG-1002 (1600 mg PO). Blood flow was measured weekly by ankle/brachial index (ABI) cuff-pressures. Plasma levels of H2S, the H2S metabolite sulfane sulfur (SS), and the NO metabolite, nitrite were measured. At day 42 post-CLI, quantitative digital subtraction angiography (DSA) vasculature was performed and number of opacified vessels counted.
Results: ABI measurements revealed a reduction to 0 following the CLI procedure. ABI improved but continued to demonstrate a persistent ischemic state with values below 0.25 at day 42 in both groups. There was no difference in ABI between the placebo and SG-1002 groups at any time point. Circulating H2S levels were similar in placebo and SG-1002 treated animals. SS levels were significantly increased from baseline to day 42 in SG-1002 treated pigs (p < 0.001) but remained unchanged in placebo treated animals. At day 42, SG-1002 treatment increase circulating NO2 levels (p < 0.05) compared to placebo. There was also an increase in NO2 levels from baseline to day 42 in the SG-1002 treated pigs (p < 0.05). DSA revealed an increase of CLI limb vessel number in SG1002 treated pigs compared to placebo (p < 0.05).
Conclusions: Treatment with the novel H2S prodrug, SG-1002, leads to an elevation in circulating metabolites of H2S and NO signaling. H2S treatment increased vascular density in the setting of severe CLI in a clinically relevant model.
Author Disclosures: A.M. Rushing: None. A.L. Scarborough: None. S.F. Boisvert: None. E. Donnarumma: None. R. Trivedi: None. D.J. Polhemus: None. D.J. Lefer: Consultant/Advisory Board; Modest; Sulfagenix. T.T. Goodchild: None.
- © 2016 by American Heart Association, Inc.