CARDIOVASCULAR MEDICINE

Phosphodiesterase type 5 inhibition does not reverse endothelial dysfunction in patients with coronary heart disease

S D Robinson¹, C A Ludlam², N A Boon³, D E Newby¹

¹ Centre for Cardiovascular Sciences, University of Edinburgh, Edinburgh, UK
² Department of Haematology, Royal Infirmary of Edinburgh, Edinburgh, UK
³ Department of Cardiology, Royal Infirmary of Edinburgh, Edinburgh, UK

Correspondence to:
Dr Simon Robinson
Centre for Cardiovascular Sciences, University of Edinburgh, Royal Infirmary of Edinburgh, 49 Little France Crescent, Edinburgh EH16 4SB, UK; simon.robinson{at}ed.ac.uk

Objectives: To investigate whether sildenafil citrate, a selective phosphodiesterase type 5 inhibitor, may improve endothelial vasomotor and fibrinolytic function in patients with coronary heart disease.

Design: Randomised double blind placebo controlled crossover study.

Patients and methods: 16 male patients with coronary heart disease and eight matched healthy men received intravenous sildenafil or placebo. Bilateral forearm blood flow and fibrinolytic parameters were measured by venous occlusion plethysmography and blood sampling in response to intrabrachial infusions of acetylcholine, substance P, sodium nitroprusside, and verapamil.

Main outcome measures: Forearm blood flow and acute release of tissue plasminogen activator.

Results: Mean arterial blood pressure fell during sildenafil infusion from a mean (SEM) of 92 (1) to 82 (1) mm Hg in patients and from 94 (1) to 82 (1) mm Hg in controls (p < 0.001 for both). Sildenafil increased endothelium independent vasodilatation with sodium nitroprusside (p < 0.05) but did not alter the blood flow response to acetylcholine or verapamil in patients or controls. Substance P caused a dose dependent increase in plasma tissue plasminogen activator antigen concentrations (p < 0.01) that was unaffected by sildenafil in either group.

Conclusions: Sildenafil does not improve peripheral endothelium dependent vasomotor or fibrinolytic function in patients with coronary heart disease. Phosphodiesterase type 5 inhibitors are unlikely to reverse the generalised vascular dysfunction seen in patients with coronary heart disease.

Abbreviations: cGMP, cyclic guanosine monophosphate; CHD, coronary heart disease; FBF, forearm blood flow; PAI-1, plasminogen activator inhibitor type 1; PDE5, phosphodiesterase type 5; t-PA, tissue plasminogen activator

Keywords: coronary heart disease; endothelium; fibrinolysis; forearm blood flow; nitric oxide

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