PATTERNS OF CHANGES IN NEUTROPHIL ADHESION MOLECULES DURING NORMOTHERMIC CARDIOPULMONARY BYPASS - A CLINICAL-STUDY

The adhesion of activated neutrophils to endothelial cells is a key fe ature of the inflammatory response to cardiopulmonary bypass (CPB) bec ause it ''unlocks'' a cascade of cytotoxic events. This adhesion is ma de possibly by the sequential involvement of two sets of neutrophil ce ll surface receptors: L-selectin and beta(2) integrins (CD11a/CD18; CD 11WCD18; CD11c/CD18). We have assessed the changes in the expression o f these adhesion molecules in ten patients who underwent various open- heart procedures with the use of ''warm'' (33.4 degrees-37 degrees C) CPB. Arterial blood samples were obtained before, during and after byp ass and processed for immunofluorescent flow cytometric analysis. CD 1 1 a expression remained unchanged throughout the study period. Convers ely, CD 11 b drastically increased early after the onset of bypass (at 15 min on bypass: 172 +/- 17 [mean fluorescence (arbitrary units), me an +/- SEM] versus 63 +/- 13 before bypass, P<0.02) and was still mark edly elevated 30 min after the end of bypass (160 +/- 38, P<0.05 versu s the pre-bypass value). CD 11 c expression underwent a similar upregu lation (at 15 min of bypass: 54 +/- 5 versus 34 +/- 5 at baseline, P<0 .01), L-selectin expression did not change significantly during the pe riod of observation. Put together, these results suggest that CPB is a ssociated with an increased adhesive potential of neutrophils, which e nhances their binding to the vascular endothelium and thereby initiate s tissue damage through the release of cytotoxic mediators from adhere nt cells. Manipulation of integrin expression could therefore represen t an effective means of alleviating the component of bypass-induced in flammatory tissue damage which is more specifically neutrophil-mediate d.