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CLINICAL RESEARCH: ASSESSING VASCULAR FUNCTION

Conduit Artery Constriction Mediated by Low Flow

A Novel Noninvasive Method for the Assessment of Vascular Function

Tommaso Gori, MD, PhD^_*,,_*, Saverio Dragoni, MD^_*, Monica Lisi, MD^_*, Giuseppe Di Stolfo, MD^_*, Serena Sonnati, MD^_*, Massimo Fineschi, MD^_* and John D. Parker, MD

^_* Department of Internal, Cardiovascular and Geriatric Medicine, University of Siena, Siena, Italy
Division of Cardiology, Department of Medicine, Mount Sinai and University Health Network Hospitals, University of Toronto, Toronto, Ontario, Canada.

Manuscript received October 24, 2007; revised manuscript received December 21, 2007, accepted January 6, 2008.

^_* Reprint requests and correspondence: Dr. Tommaso Gori, Department of Medicine 2, University Hospital of Siena, Siena, Italy. (Email: Tommaso.gori{at}utoronto.ca).

Objectives: We describe and validate a novel noninvasive method that complements the data from "traditional" flow-mediated dilation (FMD) studies.

Background: The study of peripheral vascular reactivity provides important diagnostic and prognostic information in patients with (or at risk for) cardiovascular disease.

Methods: High-resolution ultrasound and automatic computerized analysis were used to measure the diameter of the radial artery at rest and in conditions of locally decreased and increased shear stress (respectively, low–flow-mediated constriction [L-FMC] and flow-mediated dilation [FMD]). A composite end point (L-FMC + FMD) was also calculated. A total of 196 studies were performed.

Results: When the repeatability of the method was tested, the range of variation across measurements was 1.1% for L-FMC and 1.7% for FMD; the intraclass correlation coefficient was 0.80 and 0.68, respectively. Low–flow-mediated constriction, FMD, and their composite end point were significantly blunted after acute smoking, in coronary artery disease patients, and in hypertensive patients as compared with that seen in healthy age-matched volunteers (p < 0.01, analysis of variance). Low–flow-mediated constriction, but not FMD, was blunted (p < 0.05) after administration of fluconazole (an inhibitor of a cytochrome P450-derived endothelium-derived hyperpolarization factor) and aspirin (an inhibitor of cyclooxygenase). Flow-mediated dilation, but not L-FMC, was blunted (p < 0.05) by nitric oxide synthase inhibition.

Conclusions: Low–flow-mediated constriction is a simple, rapid, and accurate measure of resting arterial tone that does not require further procedures as compared with "traditional" FMD measurements. While FMD measures endothelial responses to sudden increases in shear stress, L-FMC is a measure of the response to resting shear stress levels, and, therefore, it provides additional information that is complementary to FMD.

Abbreviations and Acronyms   CAD = coronary artery disease   EDHF = endothelium-derived hyperpolarization factor   FMD = flow-mediated dilation   L-FMC = low–flow-mediated constriction   NO = nitric oxide

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