Artery Research

<Previous Article In Issue
Next Article In Issue>
Volume 16, Issue C, December 2016, Pages 94 - 95

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

Authors
Amanda M. Rushing, Amy L. Scarborough, Sarah F. Boisvert, Erminia Donnarumma, Rishi Trivedi, David J. Polhemus, David J. Lefer, Traci T. Goodchild
Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, United States
Available Online 24 November 2016.
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.

Download article (PDF)
View full text (HTML)

<Previous Article In Issue
Next Article In Issue>
Journal
Artery Research
Volume-Issue
16 - C
Pages
94 - 95
Publication Date
2016/11/24
ISSN (Online)
1876-4401
ISSN (Print)
1872-9312
DOI
10.1016/j.artres.2016.08.026How to use a DOI?
Open Access
This is an open access article distributed under the CC BY-NC license.

Cite this article

risenwbib
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  -