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, repe ated measurements of platelet aggregation in infants and small childre n are impossible due to the large blood samples required. Instead, the expression of different platelet receptors mediating platelet adhesio n (CD 36 and CD 42b), activation (CD 42b and CD 61) and aggregation (C D 41a) was measured repeatedly by flow cytometry. First, the expressio n of platelet receptors was quantified in platelet suspensions of 20 h ealthy volunteers after incubation with different concentrations of NO (0, 25, 100 and 640 ppm) and compared to changes in platelet aggregat ion and intrathrombocytic cGMP levels. It was then studied in 21 infan ts and children before, during and up to 3 days after cardiopulmonary bypass surgery. Seven of these patients required NO inhalation postope ratively. The in vitro experiments showed a reduced expression of the CD 41a, CD 42b and CD 61 receptors with increasing doses of NO, predom inantly affecting the CD 41a receptor (-11% at 100 ppm and -20% at 640 ppm). This significant effect is in keeping with the observed NO-indu ced 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 cardiopul monary 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 obser ved and analysis of variance did not reveal any significant difference between both groups of patients. Conclusions NO (greater than or equa l to 100 ppm) decreases the expression of different platelet adhesion molecules and platelet aggregation, presumably via an increase in intr acellular cGMP. However, due to the low dose range used in the clinica l setting (1-40 ppm) this is clinically not relevant. Immediately afte r cardiopulmonary bypass surgery the expression of these adhesion mole cules is reduced, but recovers on the 1st postoperative day.