What is the most appropriate methodology for detection of conduit artery endothelial dysfunction?
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.


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.
Guthikonda
Sasidhar
S
Department of Cardiology, Baylor College of Medicine, Houston, Tex, USA.
Sinkey
Christine A
CA
Haynes
William G
WG
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000493:Allopurinol / Q000008:administration & dosage* / Q000627:therapeutic use; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology*; D018592:Cross-Over Studies; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D005996:Nitroglycerin; D011379:Prognosis; D011446:Prospective Studies; D012016:Reference Values; D016037:Single-Blind Method; D012907:Smoking / Q000009:adverse effects; D018608:Ultrasonography, Doppler / Q000379:methods*; D014652:Vascular Diseases / Q000175:diagnosis / Q000503:physiopathology / Q000517:prevention & control*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D000493:Allopurinol; D014969:Xanthine Oxidase; D005996:Nitroglycerin