Simvastatin reduces myocardial injury undergoing noncoronary artery cardiac surgery: a randomized controlled trial.
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.


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.


CONCLUSIONS
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.
Division of Cardiac Surgery, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhong Shan Er Road, Guangzhou 510080, P.R. China.
Mohammed Ahmed Saad
MA
Almansob
Bo
B
Xu
Li
L
Zhou
Xiao-Xia
XX
Hu
Wen
W
Chen
Feng-Jun
FJ
Chang
Hong-Bo
HB
Ci
Jian-Ping
JP
Yao
Ying-Qi
YQ
Xu
Feng-Juan
FJ
Yao
Dong-Hong
DH
Liu
Wen-Bo
WB
Zhang
Bai-Yun
BY
Tang
Zhi-Ping
ZP
Wang
Jing-Song
JS
Ou
D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D001806:Blood Urea Nitrogen; D002097:C-Reactive Protein / Q000378:metabolism; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002316:Cardiotonic Agents / Q000627:therapeutic use; D051242:Caveolin 1 / Q000378:metabolism; D002681:China; D003402:Creatine Kinase / Q000097:blood; D003404:Creatinine / Q000097:blood; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006335:Heart Injuries / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019821:Simvastatin / Q000008:administration & dosage*; D016037:Single-Blind Method; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D016896:Treatment Outcome; D020107:Troponin T / Q000097:blood; D014463:Ultrasonography; D016277:Ventricular Function, Left / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D015415:Biomarkers; C495540:CAV1 protein, human; C508606:CXCL8 protein, human; D002316:Cardiotonic Agents; D051242:Caveolin 1; D018841:HSP90 Heat-Shock Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D020107:Troponin T; D009569:Nitric Oxide; D002097:C-Reactive Protein; D019821:Simvastatin; D003404:Creatinine; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D003402:Creatine Kinase