Response of neonatal platelets to nitric oxide in vitro.
OBJECTIVE
Several studies have demonstrated altered platelet function during nitric oxide inhalation (iNO) in adults and neonates. In vitro NO inhibits activation of fibrinogen receptor glycoprotein (GP) IIb/IIIa in a dose-dependent manner. In neonates GPIIb/IIIa response to stimulation is physiologically attenuated during the first days after birth in comparison to adults; the effects of NO on GPIIb/IIIa in neonates, however, are less established. We investigated the response of platelets from neonates, their mothers, and nonpregnant controls to the NO donor SIN-1 in vitro.


METHODS
Umbilical cord and venous (mother, controls) platelet-rich plasma was stimulated in vitro with 10 microM ADP or 0.05 U/ml thrombin in the presence or absence of 10 microM SIN-1. GPIIb/IIIa activation was determined by two-color flow cytometry.


METHODS
Delivery department of an university hospital.


METHODS
Ten healthy term neonates, their mothers and nonpregnant controls.


RESULTS
NO significantly reduced GPIIb/IIIa activation in thrombin- and ADP-stimulated platelets in all groups (p < 0.001). Neonatal platelets were significantly hyporeactive to stimulation (p < 0.05), but the relative response to SIN-1 was similar in all three groups (70 +/- 5 %).


CONCLUSIONS
The relative amount of NO-induced inhibition of GPIIb/ IIIa activation in neonates is thus similar to that of adults. However, due to the intrinsic hyporesponsiveness of neonatal platelets and NO-synergistic pharmacodynamic profiles of other drugs (e.g., prostacyclin), possible adverse effects of iNO must be considered.
Clinic of Anesthesiology and Intensive Care Medicine, Humboldt University of Berlin, Germany. didier.keh@charite.de
D
D
Keh
I
I
Kürer
J W
JW
Dudenhausen
W
W
Woltmann
K J
KJ
Falke
H
H
Gerlach
D000328:Adult; D000367:Age Factors; D001792:Blood Platelets / Q000187:drug effects*; D016022:Case-Control Studies; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000187:drug effects* / Q000378:metabolism
D020030:Nitric Oxide Donors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine