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Effects of a novel sustained release sodium nitrite formulation on critical limb ischemia in the setting of metabolic syndrome (698.3)
Author(s) -
Bradley Jessica,
Goodchild Traci,
Chang Carlos,
Polhemus David,
Otsuka Hiroyuki,
Sweet Michael,
Brown Kevin,
Robinson Scott,
Brewster Luke,
Calvert John,
Lefer David
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.698.3
Subject(s) - medicine , critical limb ischemia , ischemia , hyperaemia , blood pressure , nitric oxide , femoral artery , blood flow , anesthesia , cardiology , myocardial infarction , revascularization
Critical limb ischemia (CLI) patients have an increased risk of major amputation of 25‐40% and an annual mortality of 20%. We observed a marked attenuation of nitric oxide (NO) bioavailability and NO signaling in tissue from CLI patients. Skeletal muscle nitrite levels were significantly attenuated in CLI patients compared to controls (89.9 ± 9.3 µM vs. 428.4 ± 65.6 µM; p<0.001). We hypothesized that NO‐based therapy would enhance blood flow to the ischemic limb and ameliorate skeletal muscle necrosis in CLI. We investigated the effects of oral, sustained release (SR)‐nitrite (Theravasc Inc., Cleveland, OH) in a clinically relevant model of CLI with central obesity and metabolic syndrome. Obese Ossabaw swine (n=9 per group) were subjected to percutaneous occlusion of their common and external iliac arteries, which induced CLI. After 14 days of CLI, pigs were randomized to oral placebo or SR‐nitrite therapy (80mg/tablet 2x per day) for 35 days. Weekly, limb cuff mean blood pressure and Doppler ultrasound superficial femoral artery vessel area were measured in the ischemic limb. Despite trends for improved blood flow with SR‐nitrite there were no significant differences in ischemic limb blood pressure (A) and superficial femoral artery area (B) between study groups. Additional animals have been enrolled in the study to more fully assess the effects of SR‐nitrite therapy for the treatment of CLI. $graphic_FBCB7A13‐37D9‐43D4‐9359‐9360D8AFA024$Grant Funding Source : NIH 1R01 HL092141, NIH 1R01 HL093579, NIH 1U24 HL094373, NIH 1P20 HL113452, The CFHC