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.
RCT Entities:
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.
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