Simvastatin Increases Neutrophil Apoptosis and Reduces Inflammatory Reaction After Coronary Surgery

Background: Neutrophils play a central role in systemic inflammatory reaction after cardiopulmonary bypass. Apoptosis is significantly delayed, and this might exacerbate systemic and myocardial damage. We tested the hypothesis of whether pretreatment with simvastatin increases the apoptotic rate of neutrophils and hence reduces the entity of inflammatory reaction. Methods: Thirty patients undergoing coronary surgery with cardiopulmonary bypass were randomized to treatment with either simvastatin (40 mg/day) or placebo for 3 weeks before surgery. A group of 15 patients undergoing off-pump coronary surgery served as controls. Blood samples for detection of serum cytokine levels were obtained before anesthesia, at the end of surgery, and at 4, 24, 48, and 72 hours postoperatively. Apoptosis and indices of activation were assessed in cultured neutrophils. Results: Simvastatin significantly reduced the postoperative peak values of interleukin (IL)-6 and IL-8. The neutrophil apoptotic rate was significantly higher among neutrophils obtained from patients pretreated with simvastatin (p < 0.05 at both 8 and 24 hours) compared with placebo. Neutrophils from the statin group had depressed functional activity, as underscored by significantly lower values of CD11b (p < 0.01 at 24 hours) and a significantly less percentage of cells positive for nitro-blue tetrazolium (p < 0.01 at 12 and 24 hours) compared with placebo. Conclusions: This randomized, double-blind study indicates that statin therapy before cardiopulmonary bypass is associated with reduction of circulating markers of inflammation and increased neutrophil apoptosis. These data support a routine inclusion of statins as an adjuvant pharmacologic therapy before cardiopulmonary bypass surgery.