Simvastatin attenuates leucocyte-endothelial interactions after coronary revascularisation with cardiopulmonary bypass

Abstract

Objective: To investigate the effects of preoperative simvastatin treatment on leucocyte-endothelial interactions following coronary artery bypass surgery with cardiopulmonary bypass.

Design: Double blind crossover study. Experiments on polymorphonuclear cells (neutrophils) were done at the end of cardiopulmonary bypass and one hour postoperatively. Endothelial P-selectin expression and neutrophil/endothelial adhesion were evaluated under either normoxic or hypoxic conditions.

Setting: University hospital (tertiary referral centre).

Patients: Three groups of patients undergoing coronary bypass surgery: 20 patients taking simvastatin for cholesterol control, 16 patients not responsive to simvastatin, and 20 controls.

Main outcome measures: Expression of neutrophil CD11b and endothelial P-selectin; adhesion of neutrophils to endothelium.

Results: Cardiopulmonary bypass resulted in a significant increase in neutrophil CD11b expression in all groups. Similarly, the exposure of saphenous vein to hypoxia/reoxygenation induced an augmentation of endothelial P-selectin. However, both neutrophil CD11b expression and endothelial P-selectin exocytosis were less in the simvastatin groups than in the controls. Cardiopulmonary bypass and controlled hypoxia/reoxygenation stimulated neutrophil/endothelial adhesion, but the number of adhering cells was less in the simvastatin groups than in the controls, irrespective of the cholesterol concentration. Treatment of endothelial cells with L-NAME completely reversed the effects of simvastatin.

Conclusions: Pretreatment with simvastatin reduces neutrophil adhesion to the venous endothelium in patients undergoing coronary surgery, irrespective of its efficacy at lowering cholesterol concentration.

Figure 1

Expression of CD11b\CD18 on the surface of circulating neutrophils obtained at the end of cardiopulmonary bypass (End CPB) and one hour postoperatively (Postop). *p < 0.05 v control; **p < 0.01 v control. S, simvastatin.

Figure 2

P-selectin expression of saphenous vein endothelium exposed to normoxia (O₂ 21%) or 50 minutes of hypoxia (H/R, N₂:CO₂, 95:5). The bars represent the mean number of positive staining vein segments/examined area. **p < 0.01 v control.

Figure 3

Graph showing the per cent adhesion of unstimulated leucocytes to the endothelium of saphenous vein under basal condition, and the adhesion of neutrophils drawn one hour postoperatively to either normoxic (Postop-normoxia) or hypoxic (Postop-H/R) vein endothelium. Height bar indicates mean values. *p < 0.05 v control; **p < 0.01 v control.

Figure 4

Graph showing activated leucocyte adhesion to hypoxic saphenous vein endothelium under basal condition (base H/R), after addition of L-NAME (+L-NAME), and after treatment with either blocking monoclonal antibody (mAb) to CD111b (Ab CD11b) or blocking mAbs to both CD11b and P-selectin (Ab CD11b+P-sel ). Height bar indicate mean values. *p < 0.05 v control; **p < 0.01 v control.