Endothelial Function in Human Arteries

We will assess doses of regional L-arginine supplementation in patients undergoing elective angiography for lower extremity PAD. Assessment of EDR and EIR with IVUS in patent arteries will be performed with one of 3 doses of catheter-directed L-arginine. We will obtain plasma samples from the peripheral arteries and assay amino acid levels and protein oxidation products using mass spectrometry. These experiments will determine the optimal L-arginine supplementation dose to be used in further studies. We expect to show that L-arginine supplementation will have a more significant effect on vessels less affected by atherosclerosis, but that this effect diminishes with greater atheroma accumulation as measured by IVUS virtual histology. Also, we expect L-arginine supplementation to be most effective in vessels with low baseline L-arginine levels. Lastly, we will compare local arterial factors obtained via catheter-directed arterial sampling (NOx, L-arginine, nitrotyrosine levels) to traditional serum risk factors (glucose, HbA1c, LDL, homocysteine and hs C-reactive protein).

Inclusion criteria

• age >18 years
• symptoms of intermittent claudication, rest pain or minor tissue loss (Rutherford Category I-V)
• ABI of <.90
• angiographic demonstration of a 100mm patent segment of superficial femoral artery containing at least one distal runoff vessel

Exclusion criteria

• acute limb ischemia,
• contraindication to angiography (creatinine >2.5)
• concurrent oral anticoagulant therapy that cannot be safely withheld
• extensive tissue loss or gangrene