Endothelial Dysfunction
Conditions
Keywords
peripheral vascular disease, endothelial dysfunction, intravascular ultrasound, L-Arginine
Brief summary
Up to 30 patients with lower extremity disease scheduled to undergo diagnostic angiography will undergo baseline bloodwork and IVUS (intravascular ultrasound), followed by dosing with L-arginine to assess changes in endothelial function.
Detailed description
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).
Interventions
30 patients will receive either 50, 100 or 500mg L-arginine supplementation infused via a end-hole catheter
Sponsors
Study design
Eligibility
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| IVUS mediated assessment of endothelial-dependent (EDR) and endothelial-independent (EIR) vasorelaxation before and after catheter-directed L-arginine delivery in patent arteries. | Procedural |
Secondary
| Measure | Time frame |
|---|---|
| Local arterial factors including peripheral L-arginine and nitrotyrosine levels via mass spectrometry and morphologic parameters of plaque composition. | Procedural |