Sildenafil citrate (Viagra) does not exacerbate myocardial ischemia in canine models of coronary artery stenosis.
OBJECTIVES: Our aim was to determine whether sildenafil citrate (Viagra) unfavorably alters coronary perfusion in canine models of coronary artery stenosis. BACKGROUND: Concern has been raised that sildenafil may exacerbate ischemia in patients with coronary artery disease. However, the effects of sildenafil on coronary perfusion are largely unexplored. METHODS: Using anesthetized dogs, a micromanometer constrictor was applied to either an intact coronary artery (model of stable hypoperfusion: Protocol 1) or a site of arterial injury (model of recurrent platelet-mediated thrombosis: Protocol 2). After monitoring coronary flow for 1 h, dogs received two escalating, clinically relevant doses of sildenafil or placebo. Perfusion was assessed during the initial hour pretreatment, for 1 h following dose 1 and 1 h following dose 2 by measuring the area of the flow-time profile, normalized to baseline flow x 60 min. Interaction between sildenafil and adenosine-mediated inhibition of platelet aggregation was evaluated by in vitro platelet aggregometry (Protocol 3). RESULTS: In Protocol 1, flow-time area was maintained at 50% to 60% of baseline in both placebo- and sildenafil-treated groups. In Protocol 2, controls exhibited an expected modest, temporal adenosine-mediated improvement in flow-time area (from 40 +/- 5% to 61 +/- 7%; p < .05) while in contrast, perfusion in sildenafil-treated dogs remained unchanged (37 +/- 6% vs. 33% to 35% before vs. after treatment). In vitro aggregometry confirmed that sildenafil rendered platelets refractory to the inhibitory effects of adenosine receptor stimulation. CONCLUSIONS: Sildenafil did not exacerbate ischemia in canine models of coronary stenosis. However, in the setting of recurrent thrombosis, sildenafil-treated dogs were apparently unresponsive to the platelet inhibitory effects of endogenous adenosine.[1]References
- Sildenafil citrate (Viagra) does not exacerbate myocardial ischemia in canine models of coronary artery stenosis. Przyklenk, K., Kloner, R.A. J. Am. Coll. Cardiol. (2001) [Pubmed]
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