Assessment of endothelial function using peripheral waveform analysis: a clinical application.

OBJECTIVES The study was done to determine whether radial artery applanation tonometry can be used as a noninvasive method of assessing global endothelial function. BACKGROUND; It is known that beta(2)-receptor stimulation results in endothelial release of nitric oxide. Furthermore, for over a century glyceryl trinitrate (GTN) has been known to markedly affect the arterial pressure waveform, even in the absence of significant blood pressure (BP) changes. Therefore, it was hypothesized that the change in the peripheral pressure waveform, as measured using tonometry and quantified using the augmentation index (AIx) and in response to Salbutamol (Salb), would allow assessment of global endothelial function. METHODS The study contained three parts. In the first study, Salb (400 microg) was administered to 11 healthy subjects via inhalation after either intravenous N-omega-nitro-monomethyl-L-arginine (L-NMMA) (3 mg/kg over 5 min) or control solution (normal saline) in the supine, rested, fasted condition. The BP, heart rate and waveform responses were recorded each 5 min following Salb for 20 min. Next, GTN was given and responses recorded 5 min later. In the second study, both the reproducibility of Salb and the GTN responses were assessed in 9 subjects studied twice on separate days. In the third study, the Salb and GTN responses of 12 subjects with angiographic coronary artery disease (CAD) were compared with 10 age-matched control subjects with no atherosclerotic risk factors. RESULTS After control infusion, AIx decreased following Salb, from 50.8 +/- 4.3% to 44.8 +/- 4.2%, a change of -11.8 +/- 3.7%, p < 0.01. After L-NMMA, AIx did not significantly change following Salb (54.2 +/- 5.1% vs. 52.9 +/- 5.3%, -2.0 +/- 3.1%). The GTN-induced decreases in AIx were similar after either infusion (35.1 +/- 3.3% vs. 36.5 +/- 3.3%). Reproducibility of Salb-induced changes in AIx between studies performed on separate days was good (r = 0.80, p < 0.01). Salb-induced changes in AIx in CAD patients were significantly less compared to control subjects (-2.4 +/- 1.9% vs. -13.2 +/- 2.4%, respectively, p < 0.002). The GTN-induced changes were not significantly different (-27.6 +/- 4.2 vs. -38.9 +/- 4.4%, p = 0.07). CONCLUSIONS The peripheral arterial pressure waveform is sensitive to beta(2)-stimulation. Changes are related to nitric oxide release, are reproducible and can distinguish between clinical subject groups. Arterial waveform changes following Salb may thus provide a noninvasive method of measuring "global" arterial endothelial function.

[1]  Nitric oxide‐dependent vasodilatation of rabbit femoral artery by β2‐adrenergic stimulation or cyclic AMP elevation in vivo , 2000, British journal of pharmacology.

[2]  G. Plotnick,et al.  Changes in flow-mediated brachial artery vasoactivity with lowering of desirable cholesterol levels in healthy middle-aged men. , 1996, The American journal of cardiology.

[3]  Joseph P. Murgo,et al.  Aortic input impedance in normal man , 1980 .

[4]  J. Fleg,et al.  Effects of Age and Aerobic Capacit on Arterial Stiffness in Healthy Adults , 1993, Circulation.

[5]  J. Deanfield,et al.  Smooth muscle dysfunction occurs independently of impaired endothelium-dependent dilation in adults at risk of atherosclerosis. , 1998, Journal of the American College of Cardiology.

[6]  M. Karamanoglu,et al.  An analysis of the relationship between central aortic and peripheral upper limb pressure waves in man. , 1993, European heart journal.

[7]  B. Fetics,et al.  Estimation of Central Aortic Pressure Waveform by Mathematical Transformation of Radial Tonometry Pressure Data , 1998 .

[8]  N. S. Andrawis,et al.  Aging is associated with endothelial dysfunction in the human forearm vasculature. , 2000, Journal of the American Geriatrics Society.

[9]  D. W. Gray,et al.  Novel signal transduction pathway mediating endothelium‐dependent β‐adrenoceptor vasorelaxation in rat thoracic aorta , 1992, British journal of pharmacology.

[10]  N. Westerhof,et al.  Forward and backward waves in the arterial system. , 1972, Cardiovascular research.

[11]  R S MACKAY,et al.  Automatic Tonometer with Exact Theory: Various Biological Applications , 1960, Science.

[12]  C. Hayward,et al.  Effects of arterial dilator agents on central aortic systolic pressure and on left ventricular hydraulic load. , 1989, The American journal of cardiology.

[13]  P. Chowienczyk,et al.  Noninvasive Assessment of the Digital Volume Pulse: Comparison With the Peripheral Pressure Pulse , 2000, Hypertension.

[14]  R. Gosling,et al.  Photoplethysmographic assessment of pulse wave reflection: blunted response to endothelium-dependent beta2-adrenergic vasodilation in type II diabetes mellitus. , 1999, Journal of the American College of Cardiology.

[15]  D. Celermajer,et al.  Cigarette Smoking Is Associated With Dose‐Related and Potentially Reversible Impairment of Endothelium‐Dependent Dilation in Healthy Young Adults , 1993, Circulation.

[16]  N. Westerhof,et al.  Aortic Input Impedance in Normal Man: Relationship to Pressure Wave Forms , 1980, Circulation.

[17]  D. Glogar,et al.  Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease. , 1997, Atherosclerosis.

[18]  P. Ganz,et al.  Estrogen Improves Endothelium-Dependent, Flow-Mediated Vasodilation in Postmenopausal Women , 1994, Annals of Internal Medicine.

[19]  A P Avolio,et al.  Nitroglycerin has more favourable effects on left ventricular afterload than apparent from measurement of pressure in a peripheral artery. , 1990, European heart journal.

[20]  J M Bland,et al.  Statistical methods for assessing agreement between two methods of clinical measurement , 1986 .

[21]  R. Pini,et al.  Non‐invasive measurements of arterial compliance in hypertensive compared with normotensive adults , 1992, Journal of hypertension. Supplement : official journal of the International Society of Hypertension.

[22]  R. Furchgott,et al.  The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine , 1980, Nature.

[23]  S. Liggett,et al.  beta2-adrenergic receptor polymorphisms at amino acid 16 differentially influence agonist-stimulated blood pressure and peripheral blood flow in normal individuals. , 2000, American heart journal.

[24]  A. Yeung,et al.  Close relation of endothelial function in the human coronary and peripheral circulations. , 1995, Journal of the American College of Cardiology.

[25]  J. Ritter,et al.  Effects of inhibition of the L-arginine/nitric oxide pathway on vasodilation caused by beta-adrenergic agonists in human forearm. , 1997, Circulation.

[26]  D. Green,et al.  Simvastatin, an HMG-coenzyme A reductase inhibitor, improves endothelial function within 1 month. , 1997, Circulation.

[27]  P. Fletcher,et al.  Reproducibility of brachial ultrasonography and flow-mediated dilatation (FMD) for assessing endothelial function. , 1997, Australian and New Zealand journal of medicine.

[28]  HELEN B. HUBERT,et al.  Obesity as an Independent Risk Factor for Cardiovascular Disease: A 26‐year Follow‐up of Participants in the Framingham Heart Study , 1983, Circulation.

[29]  G. Watts,et al.  Sex differences in endothelial function in normal and hypercholesterolaemic subjects , 1994, The Lancet.

[30]  L. Mosekilde,et al.  Combined hormone replacement therapy does not protect women against the age-related decline in endothelium-dependent vasomotor function. , 1998, Circulation.

[31]  C. Hayward,et al.  Noninvasive determination of age-related changes in the human arterial pulse. , 1989, Circulation.

[32]  C. H. Chen,et al.  Estimation of central aortic pressure waveform by mathematical transformation of radial tonometry pressure. Validation of generalized transfer function. , 1997, Circulation.

[33]  S. Nakao,et al.  Non-invasive detection of endothelial dysfunction with 30 MHz transducer , 1996, The Lancet.

[34]  C H Chen,et al.  Validation of carotid artery tonometry as a means of estimating augmentation index of ascending aortic pressure. , 1996, Hypertension.

[35]  M. Sampson,et al.  Impaired vascular reactivity in insulin-dependent diabetes mellitus is related to disease duration and low density lipoprotein cholesterol levels. , 1996, Journal of the American College of Cardiology.

[36]  G. Watts,et al.  Impaired endothelium-dependent vasodilation of forearm resistance vessels in hypercholesterolaemia , 1992, The Lancet.

[37]  J. K. Lloyd,et al.  Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis , 1992, The Lancet.

[38]  D. Celermajer,et al.  Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. , 1994, Journal of the American College of Cardiology.

[39]  C. Hayward,et al.  Gender-related differences in the central arterial pressure waveform. , 1997, Journal of the American College of Cardiology.

[40]  D. Celermajer,et al.  Impaired endothelial function occurs in the systemic arteries of children with homozygous homocystinuria but not in their heterozygous parents. , 1993, Journal of the American College of Cardiology.

[41]  F Skrabal,et al.  beta-2 Adrenergic receptor variants affect resting blood pressure and agonist-induced vasodilation in young adult Caucasians. , 1999, Hypertension.

[42]  P. Ganz,et al.  Estradiol therapy combined with progesterone and endothelium-dependent vasodilation in postmenopausal women. , 1998, Circulation.

[43]  A. Beckett,et al.  AKUFO AND IBARAPA. , 1965, Lancet.

[44]  D. Spiegelhalter,et al.  Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. , 1994, Journal of the American College of Cardiology.

[45]  J. Stamler,et al.  Nitric oxide regulates basal systemic and pulmonary vascular resistance in healthy humans. , 1994, Circulation.