Inhaled nitric oxide inhibits platelet-leukocyte interactions in patients with acute respiratory distress syndrome.
BACKGROUND
In addition to its effects on platelet function, recent studies suggest that inhaled nitric oxide (NO) also influences the function of circulating leukocytes. Therefore, the aim of this work was to investigate the formation of platelet-leukocyte aggregates (PLAs) and platelet and leukocyte cell surface receptor expression during NO therapy in patients with acute respiratory distress syndrome.


METHODS
In 16 patients responding to NO therapy with an improvement in oxygenation (NO group) and in four nonresponders (control), platelet P-selectin expression, platelet fibrinogen binding, the expression CD11a on leukocytes, and the formation of PLAs were investigated at 0, 60, 120, and 180 mins of therapy or at corresponding time points by means of flow cytometry. In addition, PLA was investigated in 30 healthy volunteers during NO inhalation, in five mechanically ventilated patients without acute respiratory distress syndrome and without NO inhalation, and during NO incubation in platelet-rich plasma of ten healthy volunteers in vitro.


RESULTS
NO therapy inhibited PLA formation at 60 (13% +/- 4% in the NO group vs. 19% +/- 7% in the control group, p <.01) and 120 mins (14% +/- 4% vs. 18% +/- 7%, p <.05) and slightly decreased CD11a expression at 60 mins (152 +/- 22 arbitrary units vs. 187 +/- 36 arbitrary units, p <.05). Furthermore, besides inhibiting platelet fibrinogen binding, NO also led to a significant inhibition of P-selectin expression at 120 (38% +/- 4% vs. 43% +/- 5%, p <.05) and 180 mins (34% +/- 5% vs. 43% +/- 6%, p <.01), demonstrating a significant correlation between changes in P-selectin expression and PLA formation. In contrast, PLA formation was not influenced by mechanical ventilation in patients without acute respiratory distress syndrome. These results were further supported by additional studies showing inhibition of PLA formation in healthy volunteers as well.


CONCLUSIONS
NO-dependent inhibition of PLA formation in patients with acute respiratory distress syndrome can be explained by the inhibition in platelet P-selectin expression. Thus, this study provides rational evidence of systemic antileukocytic and antiplatelet properties of NO therapy in the clinical setting.
Gries
André
A
Department of Anesthesiology, University of Heidelberg, Heidelberg, Germany.
Herr
Axel
A
Kirsch
Sylvia
S
Günther
Christine
C
Weber
Steffen
S
Szabo
Gabor
G
Holzmann
Alexandra
A
Böttiger
Bernd W
BW
Martin
Eike
E
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001792:Blood Platelets / Q000187:drug effects* / Q000276:immunology; D040881:CD11a Antigen / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000494:pharmacology*; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects* / Q000276:immunology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D011971:Receptors, Immunologic / Q000097:blood; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D018709:Statistics, Nonparametric
D040881:CD11a Antigen; D019007:P-Selectin; D019038:Platelet Glycoprotein GPIb-IX Complex; D011971:Receptors, Immunologic; D009569:Nitric Oxide