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

Ping Hua,Jianyang Liu,Jun Tao,Dingwen Zhang,Songran Yang,Rongjun Zou,Xifeng Lin

doi:10.1155/2017/6082430

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.

Highlights

Cardiopulmonary bypass (CPB) is used in most open-heart surgeries
There were no significant differences in clinical indicators (Tables 1 and 2)
Nine patients in the simvastatin group left the study for the following reasons: two developed severe liver function abnormality after surgery, five failed to take the medication for the specified number of days, one underwent repeat thoracotomy, and one died while staying in the ICU

Summary

Introduction

Cardiopulmonary bypass (CPB) is used in most open-heart surgeries. CPB inevitably causes systemic inflammatory response and ischemia-reperfusion (IR) injury, which can negatively affect postoperative cardiac function and a patient’s long-term prognosis [1].Recent clinical studies have reported that using statins during the perioperative period can limit inflammation and oxidation, reduce cardiac muscle injury, and improve the patient’s prognosis [2,3,4], but the dosage, duration, effects, and mechanisms associated with these outcomes are not clear.Some studies have demonstrated that statins can induce cell autophagy [5]. CPB inevitably causes systemic inflammatory response and ischemia-reperfusion (IR) injury, which can negatively affect postoperative cardiac function and a patient’s long-term prognosis [1]. Recent clinical studies have reported that using statins during the perioperative period can limit inflammation and oxidation, reduce cardiac muscle injury, and improve the patient’s prognosis [2,3,4], but the dosage, duration, effects, and mechanisms associated with these outcomes are not clear. Few studies have revealed the effects of perioperative oral simvastatin on post-CPB changes in cardiac muscle autophagy or the influence of the degree of autophagy on postoperative cardiac function and prognosis [8, 9]. 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

Methods

Results

Conclusion