Abstract 16154: The LargPAD Trial: Phase IIA Evaluation of L-Arginine Supplementation in Patients With Peripheral Arterial Disease
Objective: Endothelial function is improved by L-Arginine supplementation (L-Arg) in preclinical studies. We hypothesize that endothelial function improves with catheter-directed L-Arg delivery in arteries of patients with peripheral arterial disease (PAD).
Methods: Patients with PAD (n=25, mean age 62, 48% male) requiring lower extremity angiography were enrolled. Endothelial dependent relaxation (EDR) was measured using intravascular ultrasound and a Doppler Flow wire after the infusion of acetylcholine (Ach, FDA IND). Patients received either 50 (n=5), 100 (n=10) or 500mg (n=10) L-Arg intra-arterial supplementation followed by repeat EDR measurement. IVUS derived virtual histology (IVUS-VH) of the same vessel was calculated. Endothelial independent relaxation (EIR) was measured with infusion of nitroglycerin (NTG). Levels of NOx and serum arginine were determined by laboratory analysis.
Results: Patients tolerated L-Arg infusion with no side effects or adverse events. Limb blood flow increased for all patients with Ach infusion 10-6 to 10-4 with greater increases after L-arg (68% vs. 91%, p=.085, Figure). Griess reaction analysis showed a mean NOx increase of 85% (p=.046) post L-Arg infusion. Serum arginine levels increased by 54.3% (p<.005) after limb L-arg infusion using mass spectrometry. Arterial responsiveness was intact in all vessels (EIR, 137 +/- 28% volume flow increase). IVUS-VH indicated plaque volume was 14.89 ± 5.5 mm3/cm, and plaque stratification indicated predominantly fibrous morphology (45.5%; necrotic core, 28.9%; calcium, 18.2%).
Discussion: We conclude that despite extensive atherosclerosis, endothelial function is intact in diseased lower extremity human arteries. Endothelial function can be improved by L-Arg infusion secondary to increased nitric oxide bioactivity. Further studies of L-Arg as a therapeutic modality in patients with endothelial dysfunction (i.e. acute limb ischemia) are warranted.
- © 2011 by American Heart Association, Inc.