Neutrophil Apoptosis Correlates With Systemic Inflammatory Response To Cardiopulmonary Bypass

Objective: This study was designed to observe the changes of the neutrophil counts, the rate of neutrophil apoptosis, the expression of neutrophil CDllb in peripheral blood, and the plasma neutrophil elastase concentration , and to evaluate the correlativity of neutrophil apoptosis and systemic inflammatory response to cardiopulmonary bypass.Methods: 30 patients undergoing open heart operation with cardiopulmonary bypass were studied. Blood samples were collected from the CVP line after heparin administration, before CPB30 minutes of the initiation of the CPB; 30minutes after the termination of CPB; the first morning postoperatively. The neutrophil counts were performed by blood cell counter. The rate of neutrophil apoptosis and the expression of PMN CDllb were measured with Flow Cytometry (FCM). The plasma neutrophil elastase (as an a rantiprotease-elatase complex) were determined by enzyme-linked immunosorbent assays. The morphological change of neutrophil apoptosis was examined under transmission electron microscope (TEM).Results:1. The neutrophil counts increased significantly during CPB and reached its peak value (12.76+3.90xl09/L, p<0.01) in the first morning postopertively. The neutrophil counts correlated negatively with the rate of neutrophil apoptosis (r=-0.4528,p<0.05).2. The rate of PMN apoptosis reduced significantly during CPB, and reached its lowest value (1.76+1.21%, p<0.01) at 30 minutes after the termination of CPB, and returned to the baseline value on the first morning postoperatively. The rates of PMN apoptosis correlated negatively with the duration of CPB (r=-0.4521, p<0.05).3. The expression of PMN CDllb was markly upregulated during CPB. Peak levels occurred at 30 minutes after the termination of CPB (1113.27+325.91MFI, p<0.01)and returned to the baseline level on the first morning postoperatively. Peak CDllb levels correlated negatively with PMN apoptosis rate (r=-0.6415, p<0.01).4. Plasma elastase levels elvated significantly during CPB and reached its peak at 30minutes after the termination of CPB (484.44?11.22ng/ml, p<0.01). Peak levels retured to the baseline level on the first morning postoperatively. Peak elastase levels correlated negatively with PMN apoptosis rates (r=-0.4625, p<0.01) and correlated positively with the duration of CPB (r=0.5757, p<0.01).5. Neutrophil apoptosis was showed under electron microscope. Its characters were the cell and nucleusskrinked, chromatin pyknosis and congregated along nuclear membrance and became new-moons body, cytoplasm concentrated, and the struture of organelle in cytoplasm was normal.Conclutions:1. CPB changed the neutrophil survival environment and produced many factors to depress neutrophil apoptosis. Depressed neutrophil apoptosis caused neutrophil count increased, and prolonged neutrophil survival.2. Depressed neutrophil apoptosis caused upregulation of PMN CDllb and elevation of plasma neutrophil elastase level. It caused persistence and amplification of systemic inflammation response and increased tissue injury.3. CPB induced systemic inflammation response and neutrophil apoptosis were depressed and caused systemic inflammation response further delayed.4.Through observed the change of neutrophil apoptosis, it helps us to control and treat systemic inflammatory response to CPB.