title: 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 (FMD). We further hypothesized that endothelium-derived nitric oxide (NO) was an important mediator.
  
  
  METHODS
  Patients with femoral to popliteal artery SVGs that had maintained primary patency and were at least 1 year from surgery were enrolled. High-resolution, B-mode ultrasound scans were used to measure vein graft diameter before and 1 minute after reactive hyperemia (RH) to determine 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 sublingually. Brachial artery FMD was determined by validated techniques. L-N(G)monomethyl arginine (L-NMMA; 1 mg/kg infusion over 10 minutes) was used in a subset of patients (n = 6) to competitively inhibit endothelial NO 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.
authors.affiliation: Division of Vascular and Endovascular Surgery, University of California San Francisco, San Francisco, CA 94143-0222, USA. Christopher.Owens@ucsfmedctr.org
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Owens
authors.forename: Nicole
authors.initials: N
authors.lastname: Wake
authors.forename: Michael S
authors.initials: MS
authors.lastname: Conte
authors.forename: Marie
authors.initials: M
authors.lastname: Gerhard-Herman
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Beckman
mesh_terms: D000284:Administration, Oral; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D015331:Cohort Studies; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005263:Femoral Artery / Q000503:physiopathology / Q000601:surgery*; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D007262:Infusions, Intravenous; D035002:Lower Extremity / Q000098:blood supply*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D005996:Nitroglycerin / Q000008:administration & dosage; D016491:Peripheral Vascular Diseases / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D011150:Popliteal Artery / Q000503:physiopathology / Q000601:surgery*; D012039:Regional Blood Flow; D012501:Saphenous Vein / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology / Q000637:transplantation*; D013997:Time Factors; D016896:Treatment Outcome; D018608:Ultrasonography, Doppler; D014654:Vascular Patency; D014664:Vasodilation; D014665:Vasodilator Agents / Q000008:administration & dosage; D019323:omega-N-Methylarginine / Q000008:administration & dosage
chemical_list: D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D005996:Nitroglycerin
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