Efficacy and Mechanism of Preoperative Simvastatin Therapy on Myocardial Protection after Extracorporeal Circulation.

Background: Cardiopulmonary bypass (CPB) causes systemic inflammatory response and ischemia-reperfusion (IR) injury.

Objective: To investigate the effect and mechanism of simvastatin on myocardial injury in cardiac valve surgery with CPB.

Methods: One hundred thirty patients were randomly assigned to the statin group ( = 65) or control group ( = 65). Simvastatin was administered preoperatively and postoperatively. Duration of intensive care unit stay, duration of assisted ventilation, and left ventricular ejection fraction were recorded. Plasma was analysed for troponin T (cTnT), isoenzyme of creatine kinase (CK-MB), tumor necrosis factor alpha (TNF-), interleukin-6 (IL-6), and interleukin-8 (IL-8). Ultrastructure of the myocardium and autophagosomes were observed. Beclin-1, LC3-II/I, P62, AMPK, and the phosphorylation of AMPK in cardiomyocytes were detected.

Results: Simvastatin significantly reduced the duration of assisted ventilation ( = 0.030) and ejection fraction was significantly higher in the statin group ( = 0.024). Simvastatin significantly reduced the levels of cTnT, CK-MB, TNF-, IL-6, and IL-8 ( < 0.05), reduced the expression of LC3-II/LC3-I and Beclin 1, and increased the expression of phosphorylation of AMPK. Simvastatin reduced the generation of autophagosomes and the ultrastructural injuries to myocardium.

Conclusion: Perioperative statin therapy reduced myocardial injury by regulating myocardial autophagy and activating the phosphorylation of AMPK. The registration number of this study is ChiCTR-TRC-14005164.