PO-20 A HYDROGEN SULFIDE PRODRUG AUGMENTS ANGIOGENESIS IN A SWINE MODEL OF CRITICAL LIMB ISCHEMIA VIA A NITRIC OXIDE DEPENDENT MECHANISM

DOI

10.1016/j.artres.2016.08.026How to use a DOI?

Abstract

Introduction: Despite advances in revascularization, treatments for critical limb ischemia (CLI) have been largely unsuccessful. Hydrogen sulfide (H₂S) and nitric oxide (NO), are endogenous gasotransmitters which exert potent vasodilatory and proangiogenic effects. Recent experimental evidence suggest that the proangiogenic effects of H₂S are medicated in part through the NO pathway. We sought to determine whether a novel H₂S prodrug, SG-1002 (Sulfagenix, Inc. Cleveland OH), increases NO production and promotes peripheral revascularization.

Methods: CLI was generated in Yucatan miniswine (n=17) via carotid cutdown and placement of an Amplatzer vascular plug deployed within a Viabahn stent positioned proximally in the external iliac artery. At day 7 post-CLI pigs, received daily placebo or SG-1002 (1600 mg PO). Cuff-pressures were measured weekly by ankle/brachial index (ABI). Plasma H₂S, H₂S metabolite sulfane sulfur (SS), and NO metabolite, nitrite (NO₂) were measured. At day 42 post-CLI, digital subtraction angiography (DSA) was performed and opacified vessels quantitated.

Results: ABI was reduced to 0 following CLI induction. ABI improved in both groups but continued to demonstrate persistent ischemia with values below 0.25 at day 42 and showed no difference between groups. Circulating H₂S levels were similar between groups. SS levels were 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 an increase in NO₂ levels from baseline to day 42 in SG-1002 treated pigs (p < 0.05). DSA revealed an increase of CLI limb vessel number in SG-1002 treated pigs compared to placebo (p < 0.05).

Conclusions: Treatment with the H₂S prodrug, SG-1002, results in increased metabolites of H₂S and NO signaling. H₂S treatment increased vascular density in the setting of severe CLI in a clinical relevant swine model.

Open Access

This is an open access article distributed under the CC BY-NC license.

TY  - JOUR
AU  - Amanda M. Rushing
AU  - Amy L. Scarborough
AU  - Sarah F. Boisvert
AU  - Erminia Donnarumma
AU  - Rishi Trivedi
AU  - David J. Polhemus
AU  - David J. Lefer
AU  - Traci T. Goodchild
PY  - 2016
DA  - 2016/11/24
TI  - PO-20 A HYDROGEN SULFIDE PRODRUG AUGMENTS ANGIOGENESIS IN A SWINE MODEL OF CRITICAL LIMB ISCHEMIA VIA A NITRIC OXIDE DEPENDENT MECHANISM
JO  - Artery Research
SP  - 94
EP  - 95
VL  - 16
IS  - C
SN  - 1876-4401
UR  - https://doi.org/10.1016/j.artres.2016.08.026
DO  - 10.1016/j.artres.2016.08.026
ID  - Rushing2016
ER  -