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

Biomed Res Int. 2017:2017:6082430. doi: 10.1155/2017/6082430. Epub 2017 Nov 8.

Abstract

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 (n = 65) or control group (n = 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-α), 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 (P = 0.030) and ejection fraction was significantly higher in the statin group (P = 0.024). Simvastatin significantly reduced the levels of cTnT, CK-MB, TNF-α, IL-6, and IL-8 (P < 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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Cardiopulmonary Bypass* / adverse effects
  • Cardiopulmonary Bypass* / methods
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use*
  • Creatine Kinase, MB Form / blood
  • Cytokines / blood
  • Female
  • Heart* / drug effects
  • Heart* / physiology
  • Humans
  • Male
  • Middle Aged
  • Postoperative Complications / epidemiology
  • Simvastatin / pharmacology
  • Simvastatin / therapeutic use*
  • Troponin T / blood

Substances

  • Biomarkers
  • Cardiotonic Agents
  • Cytokines
  • Troponin T
  • Simvastatin
  • Creatine Kinase, MB Form