Nitric oxide metabolites in complications after open reconstructive procedures in patients with peripheral atherosclerosis

BACKGROUND: Assessing the severity of endothelial dysfunction (ED) and making a prognosis after open reconstructive interventions in patients with peripheral atherosclerosis is complicated due to a limited number of conventional routine methods, including laboratory ones, available for establishing associations between biochemical markers and disease outcomes. AIM: This work is dedicated to the evaluation of nitric oxide (II) metabolites (nitrates and nitrites) in patients with complications following open bypass procedures on the lower extremity arteries using synthetic grafts in order to assess the severity of endothelial dysfunction and its negative sequalae. MATERIALS AND METHODS: The study involved 60 subjects with stage IIb–III chronic lower limb ischemia according to A. V. Pokrovsky–Fontaine classification (categories 3–5 Rutherford) due to atherosclerotic peripheral artery disease. Median age of the subjects was 65 (60–67); the majority of the patients were male (51 (85%). Median value of ankle-brachial index at baseline was 0.32 (0.19–0.42). All participants underwent open bypass grafting procedures using synthetic vascular grafts. Nitric (II) oxide (NO) metabolites level (nitrites and nitrates) was measured before the intervention and three months afterwards by spectrophotocolorimetry using an ELISA analyzer Stat Fax 3200 (Awareness Techonology, Inc., USA) and Griess reagent. The subjects were followed up for a year to determine the rate of development of complications such as restenosis, graft thrombosis, limb loss (major amputation), lethal outcomes, as well as disease progression, myocardial infarction, oncology, and stroke. RESULTS: Performance of a reconstructive procedure on lower extremity arteries was followed by a decrease in NO metabolites level from initial median 76.3 mcmol/ml (48–100.7) to 52.4 mcmol/ml (36.1–93.8) at three months after the intervention (р = 0.015). There was a positive correlation between the NO metabolites level at baseline (0 months) and follow-up visit (3 months) (r = +0.573). Complications within one year after bypass procedures were detected in 66.64% subjects. Baseline level of NO metabolites in patients who required an amputation within one year after the procedure was markedly elevated and reached 116.3 mcmol/ml (90–130.5) (p = 0.025); development of restenosis and lethal outcomes within one year were associated with initially low NO metabolites levels, 35.6 mcmol/ml (p = 0.036) and 33 mcmol/ml (30–36), accordingly (р = 0.043). CONCLUSIONS: Both markedly high and low levels of nitric oxide metabolites (nitrates and nitrites) levels are associated with development of severe complications after open reconstructive procedures in patients with peripheral atherosclerosis. Quantitative determination of the NO metabolites level in serum is a relatively easy and reliable method allowing for the determination of the severity of endothelial dysfunction and its sequalae in subjects after open bypass reconstructive procedures on lower extremity arteries.