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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:147.)
© 2002 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Pulse-Wave Analysis

Clinical Evaluation of a Noninvasive, Widely Applicable Method for Assessing Endothelial Function

Ian B. Wilkinson; Ian R. Hall; Helen MacCallum; Isla S. Mackenzie; Carmel M. McEniery; Bart J. van der Arend; Yae-Eun Shu; Laura S. MacKay; David J. Webb; John R. Cockcroft

From the Clinical Pharmacology Units, University of Cambridge (I.B.W., I.S.M., C.M.M.), Addenbrooke’s Hospital, Cambridge, England, and the University of Edinburgh (H.M., B.J.v.d.A., Y.-E.S., L.S.M., D.J.W.), Western General Hospital, Edinburgh, Scotland, and the Department of Cardiology (I.R.H., J.R.C.), University of Wales College of Medicine, University Hospital, Cardiff, Wales.

Correspondence to Dr I.B. Wilkinson, Clinical Pharmacology Unit, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 2QQ, UK. E-mail ibw20{at}cam.ac.uk

Currentmethods for assessing vasomotor endothelial function are impractical for use in large studies. We tested the hypothesis that pulse-wave analysis (PWA) combined with provocative pharmacological testing might provide an alternative method. Radial artery waveforms were recorded and augmentation index (AIx) was calculated from derived aortic waveforms. Thirteen subjects received sublingual nitroglycerin (NTG), inhaled albuterol, or placebo. Twelve subjects received NTG, albuterol, and placebo separately during an infusion of N^G-monomethyl-L-arginine (LNMMA) or norepinephrine. Twenty-seven hypercholesterolemic subjects and 27 controls received NTG followed by albuterol. Endothelial function was assessed by PWA and forearm blood flow in 27 subjects. Albuterol and NTG both significantly and repeatably reduced AIx (P<0.001). Only the response to albuterol was inhibited by LNMMA (-9.8±5.5% vs -4.7±2.7%; P=0.02). Baseline AIx was higher in the hypercholesterolemic subjects, who exhibited a reduced response to albuterol (P=0.02) but not to NTG when compared with matched controls. The responses to albuterol and acetylcholine were correlated (r=0.5, P=0.02). Consistent with an endothelium-dependent effect, the response to albuterol was substantially inhibited by LNMMA. Importantly, the response to albuterol was reduced in subjects with hypercholesterolemia and was correlated to that of intra-arterial acetylcholine. This methodology provides a simple, repeatable, noninvasive means of assessing endothelial function in vivo.

Key Words: hypercholesterolemia • nitric oxide • pulse-wave analysis • augmentation index • endothelial function