Sildenafil improves coronary artery patency in a canine model of platelet-mediated cyclic coronary occlusion after thrombolysis
Abstract
OBJECTIVES: We 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.
BACKGROUND: The 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.
METHODS: Cyclic 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 microg/kg bolus followed by 4 microg/kg/min infusion).
RESULTS: Cyclic 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 > or =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…
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