Sildenafil citrate (Viagra) does not exacerbate myocardial ischemia in canine models of coronary artery stenosis.
OBJECTIVE
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.
Przyklenk
K
K
Heart Institute, Good Samaritan Hospital, and Department of Medicine, University of Southern California, Los Angeles 90017-2395, USA. karinp@dnamail.com
Kloner
R A
RA
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000503:physiopathology*; D004195:Disease Models, Animal; D004285:Dogs; D010879:Piperazines / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D000241:Adenosine