P-SELECTIN EXPRESSION IN MYOCARDIUM OF CHILDREN UNDERGOING CARDIOPULMONARY BYPASS

Cardiopulmonary bypass is a planned support technique that results in a period of myocardial ischemia and reperfusion, In addition, it is as sociated with an inflammatory response likely involving endothelial fe ll activation, Zn previous studies, we showed that E-selectin and inte rcellular adhesion molecule-1 (ICAM-1) messenger ribonucleic acid (mRN A) are increased in human myocardium after cardiopulmonary bypass. We have now examined the expression of P-selectin mRNA by ribonuclease pr otection in paired atrial biopsy specimens from 12 patients before and after cardiopulmonary bypass, By means of immunocytochemistry, we hav e also examined the endothelial cell surface expression of P-selectin protein, as well as that of E-selectin and ICAM-1 in three additional patients, Patient ages ranged from 1 day to 8.5 years (median 12 month s), and cardiopulmonary bypass times ranged from 46 to 196 minutes (me dian 144 minutes), By ribonuclease protection, there was marked variab ility in the expression of P-selectin in biopsy specimens before bypas s, However, when compared with prebypass levels, P-selectin mRNA decre ased modestly in 10 of 12 patients after bypass (median decrease 1,S-f old, p = 0.016), As seen with immunocytochemistry, P-selectin protein was distributed diffusely through the vascular bed on large vessels an d small vessels before bypass but was virtually absent on capillaries in specimens taken after bypass, E-selectin, which was absent in preby pass biopsy specimens, was induced in one of the three specimens after bypass, but no change in ICAM-1 protein expression above baseline was noted, We also find that cultured human endothelial cells treated wit h tumor necrosis factor-alpha in doses which induce ICAM-1 mRNA simult aneously decrease their expression of P-selectin mRNA as compared with untreated cells, These observations suggest that endothelial P-select in is transcriptionally downregulated after cardiopulmonary bypass at times when E-selectin and ICAM-1 are induced, Furthermore, we find tha t E-selectin and ICAM-1 are expressed at times and at sites where P-se lectin is absent, Although it is possible that P-selectin may have bee n induced and lost at early times before reperfusion, these data sugge st that endothelial P-selectin plays a limited role in the inflammator y response that ensues after cardiopulmonary bypass.