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J Am Coll Cardiol, 2002; 40:521-528
© 2002 by the American College of Cardiology Foundation
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CLINICAL STUDY

Assessment of endothelial function using peripheral waveform analysis

A clinical application

Christopher S. Hayward, MD*{dagger},*, Mustafa Kraidly, MD{dagger}, Carolyn M. Webb, PhD{dagger} and Peter Collins, MD{dagger}

* St. Vincent’s Hospital, Sydney, Australia
{dagger} National Heart and Lung Institute, Royal Brompton Hospital, London, United Kingdom

Manuscript received June 4, 2001; revised manuscript received April 10, 2002, accepted May 14, 2002.

* Reprint requests and correspondence: Dr. Christopher S. Hayward, Cardiology Department, St. Vincent’s Hospital, Victoria St. Darlinghurst 2010, New South Wales, Australia.
chayward{at}stvincents.com.au

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 beta2-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 µg) 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 beta2-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.

Abbreviations and Acronyms
  AIx
  augmentation index
  ANOVA
  analysis of variance
  BMI
  body mass index
  BP
  blood pressure
  CAD
  coronary artery disease
  GTN
  glyceryl trinitrate
  HR
  heart rate
  L-NMMA
  N-{omega}-nitro-monomethyl-L-arginine
  NO
  nitric oxide
  Salb
  Salbutamol




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