Effects of cardiopulmonary bypass and inhaled nitric oxide on platelets in children with congenital heart defects.
Nitric oxide (NO) reduces platelet aggregation in vitro. However, repeated measurements of platelet aggregation in infants and small children are impossible due to the large blood samples required. Instead, the expression of different platelet receptors mediating platelet adhesion (CD 36 and CD 42b), activation (CD 42b and CD 61) and aggregation (CD 41a) was measured repeatedly by flow cytometry. First, the expression of platelet receptors was quantified in platelet suspensions of 20 healthy volunteers after incubation with different concentrations of NO (0, 25, 100 and 640 ppm) and compared to changes in platelet aggregation and intrathrombocytic cGMP levels. It was then studied in 21 infants and children before, during and up to 3 days after cardiopulmonary bypass surgery. Seven of these patients required NO inhalation postoperatively. The in vitro experiments showed a reduced expression of the CD 41a, CD 42b and CD 61 receptors with increasing doses of NO, predominantly affecting the CD 41a receptor (-11% at 100 ppm and -20% at 640 ppm). This significant effect is in keeping with the observed NO-induced inhibition of platelet aggregation (-44% at 100 ppm) and the rise in platelet cGMP levels (+69% at 100 ppm). In patients without inhaled NO, the expression of CD 41a was slightly attenuated during cardiopulmonary bypass surgery (-15%) but increased significantly afterwards (2 h: +31%, 1st day: +129%, 2nd day: +120%, 3rd day: +111%). Comparable results were obtained regarding the other adhesion molecules CD 36, CD 42b and CD 61. In patients with inhaled NO the same pattern was observed and analysis of variance did not reveal any significant difference between both groups of patients.


CONCLUSIONS
NO (> or = 100 ppm) decreases the expression of different platelet adhesion molecules and platelet aggregation, presumably via an increase in intracellular cGMP. However, due to the low dose range used in the clinical setting (1-40 ppm) this is clinically not relevant. Immediately after cardiopulmonary bypass surgery the expression of these adhesion molecules is reduced, but recovers on the 1st postoperative day.
Breuer
J
J
Department of Paediatrics, University of Tuebingen, Germany.
Leube
G
G
Mayer
P
P
Gebhardt
S
S
Sieverding
L
L
Häberle
L
L
Heinemann
M
M
Apitz
J
J
D000280:Administration, Inhalation; D000704:Analysis of Variance; D015703:Antigens, CD / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects*; D002315:Cardiopulmonary Bypass; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006157:Guanosine Monophosphate / Q000032:analysis; D006330:Heart Defects, Congenital / Q000097:blood* / Q000628:therapy*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage*; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D010976:Platelet Count
D015703:Antigens, CD; D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D006157:Guanosine Monophosphate