CLINICAL STUDY
The effect of sildenafil on human vascular function, platelet activation, and myocardial ischemia
Julian P. J. Halcox, MA, MRCP*,
Khaled R. A. Nour, MD*,
Gloria Zalos, RN*,
Rita Mincemoyer, RN*,
Myron A. Waclawiw, PhD*,
Candido E. Rivera, MD ,
Georgia Willie, MD ,
Samer Ellahham, MD and
Arshed A. Quyyumi, MD, FRCP, FACC*,*
* National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA
Department of Hematology, National Institutes of Health, Bethesda, Maryland, USA
Department of Cardiology, Washington Hospital Center, Washington, DC, USA
Manuscript received June 11, 2001;
revised manuscript received May 23, 2002,
accepted June 27, 2002.
* Reprint requests and correspondence: Dr. Arshed A. Quyyumi, Professor of Medicine (Cardiology), Emory University Hospital, Suite F606, 1364 Clifton Road N.E., Atlanta, Georgia 30322, USA.
aquyyum{at}emory.edu
OBJECTIVES: We studied the effects of sildenafil, a phosphodiesterase 5 inhibitor, on coronary and peripheral vascular function, platelet activation, and myocardial ischemia.
BACKGROUND: Nitric oxide vasodilates and inhibits platelet activation by generating cyclic guanosine 5'-monophosphate, which is metabolized by phosphodiesterase type 5.
METHODS: The effect of oral sildenafil on resting coronary vascular tone, endothelium-dependent and -independent function and platelet activation was measured in 24 patients. An additional 24 patients with coronary artery disease (CAD) and ischemia during exercise, and 12 control subjects received either 100 mg of sildenafil, 10 mg of isosorbide dinitrate (ISDN) or placebo during exercise on three separate days in a randomized, double-blind manner. Flow-mediated dilation of the brachial artery was measured, and CAD patients underwent treadmill exercise testing.
RESULTS: Sildenafil (100 mg) vasodilated epicardial coronary arteries (+6.9 ± 1.3%, p < 0.0001). Coronary epicardial and microvascular responses with acetylcholine and cold-pressor testing improved, with a greater enhancement in patients with CAD and endothelial dysfunction. Verapamil responses were unchanged. Both resting and adenosine diphosphate-stimulated platelet IIb/IIIa receptor activation was inhibited by sildenafil (p < 0.05). Brachial arteries dilated in response to sildenafil in controls. Peak flow-mediated dilation was similar, but the duration of hyperemia was prolonged after sildenafil administration (p < 0.001). Compared with placebo, ISDN improved myocardial ischemia during exercise (p < 0.05), whereas the effect of sildenafil was intermediate between the two.
CONCLUSIONS: Sildenafil dilates epicardial coronary arteries, improves endothelial dysfunction and inhibits platelet activation in patients with CAD. It has an intermediate effect on myocardial ischemia compared with ISDN and placebo.
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Abbreviations and Acronyms
| | ACH | | acetylcholine | | CAD | | coronary atherosclerosis | | cGMP | | cyclic guanosine monophosphate | | CPT | | cold-pressor testing | | CVR | | coronary vascular resistance | | D | | diameter | | FMD | | flow-mediated dilation | | ISDN | | isosorbide dinitrate | | PDE5 | | phosphodiesterase type V | | NCA | | normal coronary arteries | | NO | | nitric oxide |
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