The effect of "pump prime only" aprotinin on neutrophil CD11b upregulation during and following cardiopulmonary bypass in humans

Purpose: Cardiopulmonary bypass (CPB) induces cytokine release which, in turn, induces increased expression of the neutrophil adhesive molecule CD11b. Neutrophil CD11b is reported to be the primary neutrophil adhesive receptor responsible for post-CPB lung ana cardiac injury following neutrophil-endothelial adherence and oxidative tissue injury. Other reports demonstrate aprotinin (low dose protocol) reduces CD11b upregulation during and following CPB. This study evaluates if "pump prime only" aprotinin also reduces this neutrophil integrin (CD11b) upregulation during and following CPB. Methods: Following IRB approval and patient informed consent, 12 patients were randomized to a control group (n=6) and "pump prime only" (PP) aprotinin; 280 mg or 2×10⁶ KIU (n=6). No further aprotinin doses or glucocorticoids were administered to either group. Whole blood (20 ml, heparinized) was drawn at 1) baseline (prior to induction), 2) 50 min duration CPB, 3) 30 min after CPB termination. Neutrophils were separated by Ficoll-Hypaque density centrifugation, and integrin expression detected by double-antibody technique. Neutrophil CD11b expression was read by FACScan (Becton-Dickinson) and reported as channel fluorescence intensity minus background fluorescence. A repeated-measures analysis of variance was used to determine significance. Results: Neutrophil CD11b expression increased significantly (p<0.05) in time periods 2 and 3 in the control group only. No significant changes were seen in the PP group. Conclusions: Pump prime only aprotinin (280 mg) blunts neutrophil CD11b integrin upregulation in adult patients requiring CPB. Clinical Implications: Since the CD11b integrin is the primary neutrophil adhesive molecule responsible for neutrophil-induced post-CPB lung and myocardial reperfusion injuries, these results indicate PP only aprotinin may reduce neutrophil mediated organ injury post CPB.