Article ID Journal Published Year Pages File Type
2954124 Journal of the American College of Cardiology 2006 7 Pages PDF
Abstract

ObjectivesWe sought to assess the effect of sildenafil, a highly-specific type 5 phosphodiesterase (PDE5) inhibitor, on platelet-mediated cyclic coronary flow reductions occurring in a canine model of coronary thrombosis despite aspirin therapy.BackgroundThe PDE5 inhibitors augment the antithrombotic effects of nitric oxide in vitro and in vivo, but it has been proposed that the PDE5 inhibitor sildenafil is prothrombotic.MethodsCyclic coronary flow reductions were induced in the left anterior descending coronary artery by creation of a stenosis, endothelial injury, and thrombus formation followed by treatment with aspirin, heparin, and tissue plasminogen activator. After an initial observation period, dogs were treated with or without sildenafil (100 μg/kg bolus followed by 4 μg/kg/min infusion).ResultsCyclic coronary flow reductions ceased in five of six animals 18 ± 5 min after initiation of sildenafil but continued in all six control animals. The portion of the observation period during which the coronary artery was patent increased from 52 ± 9% to 83 ± 5% after sildenafil administration (p = 0.008) but did not differ between the first and second observation periods in untreated dogs (49 ± 11% vs. 44 ± 11%, respectively). Among animals with plasma free sildenafil levels ≥20 nmol/l, cyclic coronary flow reductions were 73 ± 12% less frequent and the time to cessation of cycling 72 ± 14% shorter than in animals with levels <20 nmol/l (p < 0.05 for both). Sildenafil transiently decreased blood pressure 7 ± 1% but did not change heart rate. Sildenafil treatment reduced ex vivo thrombin-induced platelet aggregation by 39 ± 3% (p < 0.005).ConclusionsSildenafil improves coronary patency in a canine model of platelet-mediated coronary artery thrombosis, likely via inhibition of platelet aggregation.

Related Topics
Health Sciences Medicine and Dentistry Cardiology and Cardiovascular Medicine
Authors
, , , , , ,