Simvastatin Reduces Myocardial Injury Undergoing Noncoronary Artery Cardiac Surgery

• DOI: 10.1161/atvbaha.112.252098
• Publication Date: 2012-07-14T09:30:28Z
• Authors: Mohammed Ahmed Sa...; Bo Xu; Li Zhou; Xiao-Xia Hu; Wen Chen; Feng-Jun Chang; Hong-Bo Ci; Jian-Ping Yao; Ying-Qi Xu; Feng-Juan Yao; Dong-Hong Liu; Wen-Bo Zhang; Bai-Yun Tang; Zhi-Ping Wang; Jing-Song Ou
• Keywords: Adult; Male; 0301 basic medicine; Analysis of Variance; China; Cardiotonic Agents; Interleukin-6; Caveolin 1; Interleukin-8; Middle Aged; Blood Urea Nitrogen; 3. Good health; 03 medical and health sciences; C-Reactive Protein; Heart Injuries; Creatinine; Humans; Female; HSP90 Heat-Shock Proteins; Cardiac Surgical Procedures; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Creatine Kinase; Biomarkers

Objective— Myocardial injury during cardiac surgery is a major cause of perioperative morbidity and mortality. We determined whether perioperative statin therapy is cardioprotective in patients undergoing noncoronary artery cardiac surgery and the potential mechanisms.

Methods and Results— One hundred fifty-one patients undergoing noncoronary artery cardiac surgery were randomly assigned to either a statin group (n=77) or a control group (n=74). Simvastatin (20 mg) was administered preoperatively and postoperatively. Plasma were analyzed for troponin T, isoenzyme of creatine kinase, C-reaction protein, interleukin-6, interleukin-8, creatinine, and blood urea nitrogen. Cardiac echocardiography was performed. Endothelial nitric oxide synthase (eNOS), Akt, p38, heat shock protein 90, caveolin-1, and nitric oxide (NO) in the heart were detected. Simvastatin significantly reduced plasma troponin T, isoenzyme of creatine kinase, C-reaction protein, blood urea nitrogen , creatinine, interleukin-6, interleukin-8, and the requirement of inotropic postoperatively. Simvastatin increased NO production, the expression of eNOS and phosphorylation at serine1177, phosphorylation of Akt, expression of heat shock protein 90, heat shock protein 90 association with eNOS and decreased eNOS phosphorylation at threonine 495, phosphorylation of p38, and expression of caveolin-1. Simvastatin also improved cardiac function postoperatively.

Conclusion— Perioperative statin therapy can improve cardiac function and renal function by reducing myocardial injury and inflammatory response through activating Akt-eNOS and attenuating p38 signaling pathways in patients undergoing noncoronary artery cardiac surgery.

Clinical Trial Registration—

URL:

http://www.clinicaltrials.gov

. Unique identifier: NCT01178710.