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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:1172.)
© 2007 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

What Is the Most Appropriate Methodology for Detection of Conduit Artery Endothelial Dysfunction?

Sasidhar Guthikonda; Christine A. Sinkey; William G. Haynes

From the Department of Cardiology (S.G.), Baylor College of Medicine, Houston, Tex; and the Department of Internal Medicine and General Clinical Research Center (C.A.S., W.G.H.), University of Iowa College of Medicine, Iowa City.

Correspondence to William G. Haynes MD FRCPE, General Clinical Research Center (157 MRF), University of Iowa College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242. E-mail william-g-haynes{at}uiowa.edu

Background— Use of upper-arm arterial occlusion to induce reactive hyperemia, and endothelium-dependent flow-mediated dilation (FMD) of the brachial artery, induces greater conduit vessel dilatation than lower-arm occlusion. However, brachial artery ischemia after upper arm arterial occlusion may make this approach unreliable. We studied whether upper or lower arm occlusions differ in their ability to detect endothelial dysfunction in cigarette smokers, and its improvement with an antioxidant strategy.

Methods and Results— Ten cigarette smokers with a >20 pack year history and 10 age- and gender-matched healthy controls participated in a 2-phase randomized controlled study of xanthine oxidase inhibition, using a 600-mg oral dose of allopurinol administered beforehand. Endothelium-dependent dilatation was assessed using ultrasound-Doppler after lower and upper arm occlusion. After lower arm occlusion, FMD was significantly impaired in smokers compared with controls (3.8±1.1% versus 8.7±2.2%; P=0.001). However, after upper arm occlusion, brachial artery dilatation in smokers was higher (11.8±2.7%; P<0.0001 versus lower arm) and did not differ from controls (9.4±2.9%; P=0.3). There was no difference in endothelium-independent dilatation to sublingual nitroglycerin between smokers and controls. Inhibition of xanthine oxidase with allopurinol improved lower arm FMD (3.8±1.1 to 10.1±1.9%; P<0.0001), but did not improve upper arm FMD (11.8±2.7 to 14.1±3.7%; P=0.4).

Conclusions— Although upper arm occlusion induces robust brachial vasodilatation, it cannot detect endothelial dysfunction induced by smoking or its improvement by inhibition of xanthine oxidase. The increase in brachial artery diameter with upper arm occlusion may be confounded by ischemia of the artery. Conduit artery FMD after release of lower arm occlusion appears to be a more valid method for assessment of endothelial function in humans.

Reactive hyperemia after lower arm arterial occlusion (LAO) is used to study conduit vessel endothelial function. Upper arm brachial artery occlusion (UAO) has been suggested as an alternative and better method to assess endothelial function. We tested upper arm occlusion to evaluate endothelial dysfunction in smokers before and after xanthine oxidase inhibition with allopurinol. LAO demonstrated significant impairment in endothelial function in smokers and improved with allopurinol, whereas UAO did not. Responses to nitroglycerin and in controls were not significantly different. In conclusion, LAO is better means of studying endothelial dysfunction than UAO.

Key Words: Doppler ultrasound • risk factors • flow-mediated dilation • endothelium

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