Pulse-Wave Analysis: Clinical Evaluation of a Noninvasive, Widely Applicable Method for Assessing Endothelial Function

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 22; no. 1; pp. 147 - 152
• Main Authors: Wilkinson, Ian B., Hall, Ian R., MacCallum, Helen, Mackenzie, Isla S., McEniery, Carmel M., van der Arend, Bart J., Shu, Yae-Eun, MacKay, Laura S., Webb, David J., Cockcroft, John R.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.01.2002; Hagerstown, MD Lippincott
• Subjects: Acetylcholine - pharmacology; Adrenergic beta-Agonists - blood; Adrenergic beta-Agonists - pharmacology; Adult; Albuterol - blood; Albuterol - pharmacology; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Blood Pressure - physiology; Cardiology. Vascular system; Compliance; Double-Blind Method; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Enzyme Inhibitors; Female; Forearm - blood supply; Humans; Hypercholesterolemia - blood; Hypercholesterolemia - physiopathology; Male; Medical sciences; Middle Aged; Nitroglycerin - pharmacology; Norepinephrine - pharmacology; omega-N-Methylarginine; Plethysmography - drug effects; Plethysmography - methods; Radial Artery - drug effects; Radial Artery - physiology; Regional Blood Flow - drug effects; Regional Blood Flow - physiology; Reproducibility of Results; Vasoconstrictor Agents - pharmacology; Vasodilator Agents - pharmacology; Vasomotor System - drug effects; Vasomotor System - physiology; Human; Pathogenesis; Pulse; Cardiovascular disease; Metabolic diseases; Lipids; Hyperlipoproteinemia; Endothelium; Vascular disease; Wave; Hypercholesterolemia; Analysis; Atherosclerosis; Risk factor; Hemodynamics; Dyslipemia
• ISSN: 1079-5642; 1524-4636; 1524-4636
• DOI: 10.1161/hq0102.101770

Current methods 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-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.