INHALED NITRIC-OXIDE INHIBITS HUMAN PLATELET-AGGREGATION, P-SELECTIN EXPRESSION, AND FIBRINOGEN BINDING IN-VITRO AND IN-VIVO

Background-Recent data suggest that inhaled NO can inhibit platelet ag gregation. This study investigates whether inhaled NO affects the expr ession level and avidity of platelet membrane receptors that mediate p latelet adhesion and aggregation. Methods and Results-In 30 healthy vo lunteers. platelet-rich plasma was incubated with an air/5% CO2 mixtur e containing 0, 100, 450, and 884 ppm inhaled NO. ADP-and collagen-ind uced platelet aggregation, the membrane expression of P-selectin, and the binding of fibrinogen to the platelet glycoprotein (GP) IIb/IIIa r eceptor were determined before (t(0)) and during the 240 minutes of in cubation. In addition, eight patients suffering from severe adult resp iratory distress syndrome (ARDS) were investigated before and 120 minu tes after the beginning of administration of 10 ppm inhaled NO. In vit ro, NO led to a dose-dependent inhibition of both ADP-induced (3+/-3% at 884 ppm versus 70+/-6% at 0 ppm after 240 minutes; P<.001) and coll agen-induced (13+/-5% versus 62+/-5%; P<.01) platelet aggregation. Fur thermore, P-selectin expression (36+/-7% of t(0) value: P<.01) and fib rinogen binding (33+/-11%; P<.01) were inhibited. In patients with ARD S, after two who did not respond to NO inhalation with an improvement in oxygenation had been excluded, an increase in plasma cGMP, prolonga tion of in vitro bleeding time, and inhibition of platelet aggregation and P-selectin expression were observed, and fibrinogen binding was a lso inhibited (19+/-7% versus 30+/-8%; P<.05). Conclusions-NO-dependen t inhibition of platelet aggregation may be caused by a decrease in fi brinogen binding to the platelet GP IIb/IIIa receptor.