Vikram S. Kashyap1, Ryan O. Lakin1, Lindsay Feiten2, Paul Bishop2, Timur P. Sarac2
1University Hospitals Case Medical Center, Cleveland, OH; 2The Cleveland Clinic, Cleveland, OH.
OBJECTIVES: Endothelial function has been measured in human brachial and coronary arteries, but not in lower extremity arteries affected by atherosclerosis. We describe a novel, first-in-man, evaluation of endothelial function in patients with peripheral arterial disease (PAD) of the superficial femoral arteries (SFA).
METHODS: Patients with PAD (n=25) requiring lower extremity angiography were enrolled. Endothelial dependent relaxation (EDR) was measured using intravascular ultrasound and a Doppler Flow wire after acetylcholine infusion (Ach). IVUS derived virtual histology (IVUS-VH) of the same vessel was calculated. Endothelial independent relaxation (EIR) was measured with infusion of nitroglycerin (NTG, 200 ug).
RESULTS: Patients (mean age 62, 48% male) had a history of hypertension (80%), coronary disease (32%), and diabetes (56%). The mean SFA diameter was 5.2±0.99 mm (range 3.2-6.9 mm). EDR increased over baseline for all patients with Ach infusion 10-6-10-4. Diameter (0.5% at Ach10-4) and area (1.83% at Ach10-4) changes in the diseased SFA were modest. But, average velocity of blood flow (APV) significantly increased 26.2, 46 and 63% with Ach infusion 10-6-10-4. Calculations of blood flow (mm2/sec, 67% change, Ach10-4) and limb volume flow (mm3/sec, 68.1%, Ach10-4) were performed. Lower extremity NOx levels approximated systemic venous levels (P=0.6). NTG infusion indicated normal smooth muscle responsiveness (3.3% diameter, 8.9% area, and 116% velocity change over baseline). IVUS-VH plaque stratification indicated predominantly fibrous morphology (45.5%; necrotic core, 28.9%; calcium, 18.2%). Atheroma burden was 14.89 ± 5.5 mm 3/cm and did not correlate with endothelial responsiveness.
CONCLUSIONS: Endothelial function can be measured directly in human lower extremity arteries. Despite extensive atherosclerosis, endothelial function is still intact. These data support the application of regional endothelial-specific biological therapies in patients with PAD.
AUTHOR DISCLOSURES: P. Bishop, Nothing to disclose; L. Feiten, Nothing to disclose; V. S. Kashyap, NIH, AVA, Research Grants; R. O. Lakin, Nothing to disclose; T. P. Sarac, Nothing to disclose.
Posted April 2012