In vivo human lower extremity saphenous vein bypass grafts manifest flow mediated vasodilation

Abstract

Objective As in arteries, venous endothelium modulates vessel homeostasis and tone. The effect of an arterialized environment on venous endothelial function remains poorly understood. In particular, regulation of saphenous vein graft (SVG) blood flow and lumen caliber remains undefined. We hypothesized that mature SVGs would exhibit endothelium-dependent, flow-mediated vasodilation. We further hypothesized that endothelium-derived nitric oxide (NO) was an important mediator of vascular tone. Methods Patients with femoral to popliteal artery SVGs that had maintained primary patency and were at least one year from surgery were enrolled. High-resolution, B-mode ultrasound was used to measure vein graft diameter before and one minute after reactive hyperemia (RH) to determine flow-mediated vasodilation (FMD). RH was created through application of 220 mm Hg to the calf for 5 minutes with a sphygmomanometric cuff. After a 10 minute recovery period, nitroglycerin-mediated, endothelium-independent vasodilation was measured 3 minutes after administration of nitroglycerin 0.4 mg SL. Brachial artery FMD was also measured. L-NG monomethyl arginine (L-NMMA; 1 mg/kg infusion over ten minutes) was used in a subset of patients (N=6) to competitively inhibit endothelial nitric oxide synthase. Results Nineteen subjects were enrolled. The median age of the SVGs was 34.6 (21.0–49.7) months. SVG flow-mediated, endothelium-dependent vasodilation was measured at 5.28% ± 3.1% mean change in lumen diameter (range 1.99% – 9.36%, p<.0001 for diameter change). Nitroglycerin-mediated, vasodilation was 3.7% ± 1.0%, (range .16% – 10.04%, P<.005). Intravenous administration of L-NMMA abolished SVG FMD (5.7 ± 1.4% before L-NMMA vs 0.01 ± 0.01% during L-NMMA infusion, p=.0088) and attenuated brachial artery FMD (7.54% ± 1.0% vs 5.7± 1.4; p=.05). Conclusions SVGs manifest flow-mediated, endothelium-dependent and nitroglycerin-mediated, endothelium-independent vasodilation. Vein graft endothelium-dependent FMD is likely mediated by NO. Further investigation will be required to determine the role of endothelial function in vein graft patency.

Atorvastatin-Loaded Hydrogel Affects the Smooth Muscle Cells of Human Veins

“…The implantation of a vein graft into arterial circulation often results in the development of IH, leading to vessel stenosis (Owens et al, 2009;Owens, 2010). This process is associated with the dedifferentiation of HSMCs, which turn from a contractile to a secretory phenotype, characterized by increased proliferation and migration (Owens et al, 2004;Mitra et al, 2006;Alexander and Owens, 2012;Nguyen et al, 2013).…”

Carotid Proliferative Plaque Formation in a Canine Model of Chronic Hypertension

“…These distributions of proliferative plaque formation are different from the atherosclerotic lesions induced by hyperlipidemia, which is mainly located in both the aorta and carotid arteries. 24 …”

Association between n-3 polyunsaturated fatty acid content of red blood cells and inflammatory biomarkers in patients with peripheral artery disease

“…Flow-mediated vasodilation was performed according to current guidelines and standards 36,37 as already described by our group 38 and other investigators 39 . Subjects were asked to fast (≥ 8 hours) and be free of nicotine (≥ 4 hours).…”

“…2,3 Several studies have demonstrated that C-reactive protein (CRP) and other inflammatory markers, including interleukin-6 (IL-6) and intercellular-adhesion-molecule-1 (ICAM-1), are elevated in patients with PAD. 4–6 Inflammation increases the risk of progression to PAD and of its severity, 7–10 and more importantly, is a predictor of increased mortality in patients with PAD. 11–13 …”