Endothelial Function in Human Arteries

Study Overview
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Brief Summary
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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
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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).

Official Title
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Endothelial Function in Human Arteries

Conditions
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Endothelial Dysfunction

Intervention / Treatment
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* Drug: L-arginine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L-arginine<br>Assess the effects of regional L-arginine supplementation in patients with chronic lower extremity occlusive disease undergoing angiography | Drug: L-arginine<br>* 30 patients will receive either 50, 100 or 500mg L-arginine supplementation infused via a end-hole catheter<br>* Other names: Nitric oxide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local arterial factors including peripheral L-arginine and nitrotyrosine levels via mass spectrometry and morphologic parameters of plaque composition. |  | Procedural | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peripheral vascular disease, endothelial dysfunction, intravascular ultrasound, L-Arginine