(Circulation. 1996;94:1919-1926.)
© 1996 American Heart Association, Inc.
Articles |
Inhaled Nitric Oxide Increases Coronary Artery Patency After Thrombolysis
the Department of Anesthesia (C.A., W.E.H., W.M.Z.), the Cardiac Unit (K.D.B., P.R.M., J.L.G., R.H., H.K.G., M.J.S.), and Cardiovascular Research Center (K.D.B.) of the Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Mass.
Correspondence to Marc J. Semigran, MD, Cardiac Unit, Massachusetts General Hospital, Bulfinch 211, Boston, MA 02114. E-mail semigran@olorin.mgh.harvard.edu.
Background Nitric oxide (NO) and nitrosovasodilators that release NO inhibit platelet aggregation. The antithrombotic effect of intravenously infused nitrosovasodilators is usually accompanied by systemic vasodilation. Inhaled NO is a pulmonary vasodilator that does not produce systemic hemodynamic effects. This study examines the antithrombotic effect of inhaled NO in a canine model of platelet-mediated coronary artery reocclusion after thrombolysis.
Methods and Results In 25 anesthetized dogs, a segment of the left anterior descending coronary artery was traumatized and a high-grade stenosis created. Thrombus was injected at this site, and tissue plasminogen activator was administered, producing cyclic flow variations (CFVs) in 24 of 25 dogs. CFV frequency was 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% while breathing 20 ppm NO (P<.01) and from 49±3% to 75±7% while breathing 80 ppm NO (P<.01). The increased CAPR during 80 ppm NO administration 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 did not reverse the effect of the thromboxane A2 agonist U-46619. In vitro ADP-induced platelet aggregation was inhibited by NO gas.
Conclusions Inhaled NO at concentrations of 20 and 80 ppm increases coronary patency and decreases CFV frequency in a canine model of platelet-mediated coronary reocclusion after thrombolysis without producing systemic hemodynamic effects.
Key Words: nitric oxide • thrombolysis • thrombus
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