Effects of a novel hydrogen sulfide prodrug in a porcine model of acute limb ischemia
| Autor: | J. Stephen Jenkins, Jeffrey D. Schumacher, Zhen Li, Samuel E. Victoria, Kevin Au, David J. Lefer, Erminia Donnarumma, Amanda M. Rushing, David J. Polhemus, Traci T. Goodchild |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Swine
medicine.medical_treatment Neovascularization Physiologic 030204 cardiovascular system & hematology Pharmacology Nitric Oxide Placebo Revascularization Article Nitric oxide Peripheral Arterial Disease 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Ischemia Occlusion medicine Animals Prodrugs Hydrogen Sulfide 030212 general & internal medicine Nitrites Vascular disease business.industry Extremities Prodrug equipment and supplies medicine.disease Coronary Vessels Peripheral Vasodilation Disease Models Animal Oxidative Stress medicine.anatomical_structure chemistry Regional Blood Flow Acute Disease Swine Miniature Angiogenesis Inducing Agents Female Surgery Cardiology and Cardiovascular Medicine business Signal Transduction Artery |
| Zdroj: | J Vasc Surg |
| ISSN: | 0741-5214 |
| Popis: | OBJECTIVE. Previous studies have shown hydrogen sulfide (H(2)S) exerts potent proangiogenic properties under in vitro conditions and in rodent models. We sought to determine whether a novel H(2)S prodrug promotes peripheral revascularization in a swine model of acute limb ischemia (ALI). METHODS AND RESULTS. ALI was induced in 17 female miniswine via intravascular occlusion of the external iliac. At day 7 post- ALI induction, miniswine (n = 17) were randomized to received placebo or the H(2)S pro-drug, SG-1002 (800 mg PO BID), for 35 days. At day 35 SG-1002 increased circulating levels of H(2)S (5.0 ± 1.2 μmol/L vs. 1.8 ± 0.50 μmol/L; p < 0.05), sulfane sulfur (10.6 ± 2.3 μmol/L vs. 2.6 ± 0.8 μmol/L; p < 0.05), and nitrite (0.5 ± 0.05 μmol/L vs. 0.3 ± 0.03 μmol/L; p < 0.005) compared to placebo. SG-1002 therapy increased angiographic scoring in ischemic limb vessel number (27.6 ± 1.6 vs. 22.2 ± 1.8; p < 0.05) compared to placebo. Treatment with SG-1002 preserved existing capillaries in ischemic limbs (128.3 ± 18.7 vs. 79.0 ± 9.8 capillaries/mm(2); p < 0.05) compared to placebo. Interestingly, treatment with SG-1002 also improved coronary vasorelaxation responses to bradykinin and substance P in miniswine with ALI. CONCLUSIONS. Our results suggest that daily administration of the H(2)S prodrug, SG-1002, leads to an elevation in circulating H(2)S and NO signaling and preserves vessel number and density in ischemic limbs. Furthermore, SG-1002 therapy improved endothelial-dependent coronary artery vasorelaxation in the setting of ALI. Our data demonstrate that SG-1002 preserves the vascular architecture in ischemic limbs and exerts vascular protective effects in the coronary vasculature in a model of peripheral vascular disease. |
| Databáze: | OpenAIRE |
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