Randomized, placebo-controlled, blinded and cross-matched study on the antiplatelet effect of inhaled nitric oxide in healthy volunteers.
The platelet inhibitory effect of 0-40 ppm inhaled nitric oxide (NO) was investigated in healthy men and women. In both groups, ADP-and collagen-induced platelet aggregation was significantly inhibited 20 (T20) and 40 min (T40) after the beginning of inhalation of 5, 10, and 40 ppm. Moreover, in both men and women, the in vitro bleeding time was significantly prolonged at T20 and T40 during inhalation of 40 ppm. Inhalation of NO also inhibited P-selectin expression at 5, 10, and 40 ppm and fibrinogen binding to the GPIIb/IIIa-receptor at 40 ppm. In conclusion, in healthy volunteers, the platelet inhibitory effect of inhaled NO was not dose-related, since it was significant at 5 and 10 ppm but did not increase during the administration of higher NO concentrations. In addition, gender-related differences were only observed in ADP-induced platelet aggregation at 10 ppm and in bleeding time prolongation at 40 ppm.
Gries
A
A
Department of Anesthesiology, University of Heidelberg, Germany. ANDRE_GRIES@med.uni-heidelberg.de
Herr
A
A
Motsch
J
J
Holzmann
A
A
Weimann
J
J
Taut
F
F
Erbe
N
N
Bode
C
C
Martin
E
E
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000280:Administration, Inhalation; D000328:Adult; D001780:Blood Coagulation Tests; D003094:Collagen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005340:Fibrinogen / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D016555:Matched-Pair Analysis; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000008:administration & dosage* / Q000494:pharmacology*; D019007:P-Selectin / Q000187:drug effects; D010919:Placebos; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D010976:Platelet Count; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000187:drug effects / Q000378:metabolism; D012737:Sex Factors; D013997:Time Factors
D009566:Nitrates; D019007:P-Selectin; D010919:Placebos; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; D005340:Fibrinogen; D003094:Collagen