From the Department of Anesthesiology and Department of Cardiology (C.B.,
K.P.), University of Heidelberg, Germany.
Correspondence to André Gries, MD, Department of Anesthesiology, University of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany. E-mail andre_gries{at}krzmail.krz.uni-heidelberg.de
Background—Recent data suggest
that inhaled NO can inhibit platelet aggregation. This study
investigates whether inhaled NO affects the expression level and
avidity of platelet membrane receptors that mediate platelet
adhesion and aggregation.
Methods and Results—In 30 healthy volunteers, platelet-rich
plasma was incubated with an air/5% CO2 mixture containing
0, 100, 450, and 884 ppm inhaled NO. ADP- and collagen-induced
platelet aggregation, the membrane expression of P-selectin, and
the binding of fibrinogen to the platelet glycoprotein
(GP) IIb/IIIa receptor were determined before (t0) and
during the 240 minutes of incubation. In addition, eight patients
suffering from severe adult respiratory distress syndrome (ARDS) were
investigated before and 120 minutes after the beginning of
administration of 10 ppm inhaled NO. In vitro, 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
collagen-induced (13±5% versus 62±5%; P<.01)
platelet aggregation. Furthermore, P-selectin expression (36±7%
of t0 value; P<.01) and fibrinogen binding
(33±11%; P<.01) were inhibited. In patients with
ARDS, after two who did not respond to NO inhalation with an
improvement in oxygenation had been excluded, an
increase in plasma cGMP, prolongation of in vitro bleeding time, and
inhibition of platelet aggregation and P-selectin expression were
observed, and fibrinogen binding was also inhibited (19±7% versus
30±8%; P<.05).
Conclusions—NO-dependent inhibition of platelet aggregation
may be caused by a decrease in fibrinogen binding to the platelet
GP IIb/IIIa receptor.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Inhaled Nitric Oxide Inhibits Human Platelet Aggregation, P-Selectin Expression, and Fibrinogen Binding In Vitro and In Vivo
Key Words: platelets • P-selectin • fibrinogen • nitric oxide • respiration
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