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).

Conclusion: 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.

Figures

Figure 1

Schematic of lower extremity cuff-induced ischemia technique. The superficial femoral artery is occluded and a saphenous vein bypass is shown. The cuff is placed distal to the distal anastomosis and inflated to supra-systolic pressures, a. Doppler spectral waveform of the vein graft demonstrating baseline, b, and hyperemic flow patterns, c.

Figure 1

Schematic of lower extremity cuff-induced ischemia technique. The superficial femoral artery is occluded and a saphenous vein bypass is shown. The cuff is placed distal to the distal anastomosis and inflated to supra-systolic pressures, a. Doppler spectral waveform of the vein graft demonstrating baseline, b, and hyperemic flow patterns, c.

Figure 1

Schematic of lower extremity cuff-induced ischemia technique. The superficial femoral artery is occluded and a saphenous vein bypass is shown. The cuff is placed distal to the distal anastomosis and inflated to supra-systolic pressures, a. Doppler spectral waveform of the vein graft demonstrating baseline, b, and hyperemic flow patterns, c.

Figure 2

Figure 2a Volumetric flow through human saphenous vein grafts under basal and hyperemic conditions and pre and post 0.4 mg sublingual nitroglycerin. Figure 2b Endothelium-dependent and-independent vasodilatation in human saphenous vein bypass grafts. Baseline reflects baseline vein graft diameter. RH reactive hyperemia, TNG, nitroglycerin. Figure 2c Flow mediated (FMD) and nitroglycerin mediated (NMD) vasodilatation in human saphenous vein grafts.

Figure 2

Figure 2a Volumetric flow through human saphenous vein grafts under basal and hyperemic conditions and pre and post 0.4 mg sublingual nitroglycerin. Figure 2b Endothelium-dependent and-independent vasodilatation in human saphenous vein bypass grafts. Baseline reflects baseline vein graft diameter. RH reactive hyperemia, TNG, nitroglycerin. Figure 2c Flow mediated (FMD) and nitroglycerin mediated (NMD) vasodilatation in human saphenous vein grafts.

Figure 2

Figure 2a Volumetric flow through human saphenous vein grafts under basal and hyperemic conditions and pre and post 0.4 mg sublingual nitroglycerin. Figure 2b Endothelium-dependent and-independent vasodilatation in human saphenous vein bypass grafts. Baseline reflects baseline vein graft diameter. RH reactive hyperemia, TNG, nitroglycerin. Figure 2c Flow mediated (FMD) and nitroglycerin mediated (NMD) vasodilatation in human saphenous vein grafts.

Figure 3

Regression analysis demonstrating a significant positive correlation between brachial artery and vein graft flow mediated dilation once normalized to RH flow stimulus, r=.64, P=.004.

Figure 4

The contribution of Nitric oxide (NO) to brachial artery and vein graft flow mediated dilatation (FMD) was examined by systemically infusing L-NG monomethyl arginine (LNMMA). While NO contributes to brachial artery FMD in atherosclerotic patients, P=.05, a, NO is likely the primary mediator of vein graft FMD, P=.0088, b.

Figure 4

The contribution of Nitric oxide (NO) to brachial artery and vein graft flow mediated dilatation (FMD) was examined by systemically infusing L-NG monomethyl arginine (LNMMA). While NO contributes to brachial artery FMD in atherosclerotic patients, P=.05, a, NO is likely the primary mediator of vein graft FMD, P=.0088, b.