INHALED NITRIC-OXIDE INCREASES CORONARY-ARTERY PATENCY AFTER THROMBOLYSIS

Background Nitric oxide (NO) and nitrosovasodilators that release NO i nhibit platelet aggregation. The antithrombotic effect of intravenousl y infused nitrosovasodilators is usually accompanied by systemic vasod ilation. Inhaled NO is a pulmonary vasodilator that does not produce s ystemic hemodynamic effects. This study examines the antithrombotic ef fect of inhaled NO in a canine model of platelet-mediated coronary art ery reocclusion after thrombolysis. Methods and Results In 25 anesthet ized dogs, a segment of the left anterior descending coronary artery w as traumatized and a high-grade stenosis created. Thrombus was injecte d at this site, and tissue plasminogen activator was administered, pro ducing cyclic flow variations (CFVs) in 24 of 25 dogs. CFV frequency w as unchanged in dogs not breathing NO but decreased by 35+/-9% (P<.05) and 53+/-7% (P<.01) while dogs breathed 20 and 80 parts per million ( ppm) NO, respectively. The coronary artery patency ratio (fraction of time during which the coronary artery was patent; CAPR) was unchanged in dogs not treated with NO but increased from 51+/-7% to 64+/-8% whil e breathing 20 ppm NO (P<.01) and from 49+/-3% to 75+/-7% while breath ing 80 ppm NO (P<.01). The increased CAPR during 80 ppm NO administrat ion persisted during a 45-minute posttreatment period (70+/-7%, P<.05 versus baseline). NO inhalation did not change systemic hemodynamics. In a pharmacological model of coronary vasoconstriction, inhaled NO di d not reverse the effect of the thromboxane A(2) agonist U-46619. In v itro ADP-induced platelet aggregation was inhibited by NO gas. Conclus ions Inhaled NO at concentrations of 20 and 80 ppm increases coronary patency and decreases CFV frequency in a canine model of platelet-medi ated coronary reocclusion after thrombolysis without producing systemi c hemodynamic effects.