Myocardial Redox State Predicts In-Hospital Clinical Outcome After Cardiac Surgery Effects of Short-Term Pre-Operative Statin Treatment
Myocardial Redox State Predicts In-Hospital Clinical Outcome After Cardiac Surgery Effects of Short-Term Pre-Operative Statin Treatment
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DOI：
10.1016/j.jacc.2011.08.062
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发表时间：
2012-01-03
影响因子：
24
通讯作者：
Casadei, Barbara
中科院分区：
文献类型：
--
作者：
Antoniades, Charalambos;Demosthenous, Michael;Casadei, Barbara
目的探讨心肌氧化还原状态在心脏手术后院内并发症发生中的作用，以及他汀类药物对心肌氧化还原状态的影响。他汀类药物可改善心脏手术后的临床预后，但其是否通过改变心肌氧化还原状态发挥作用尚不清楚。方法定量分析303例心脏手术患者右心耳（RAA）样品中心肌超氧阴离子（O-2）和过氧亚硝酸盐（ONOO-）及其酶源，随访至出院，42例患者术前随机接受阿托伐他汀40mg /d或安慰剂治疗3 d。在26例体外暴露于阿托伐他汀的RAA样本中，研究了阿托伐他汀改变心肌氧化还原状态的机制。结果心房O-2(-)（主要来源于烟酰胺腺嘌呤二核苷酸磷酸[NADPH]氧化酶）和ONOO-与房颤风险增加、术后肌力支持需求和住院时间长短独立相关。术前阿托伐他汀治疗可抑制心房NADPH氧化酶活性和心肌O-2（-）和ONOO-的产生。RAA样品与阿托伐他汀体外孵育诱导甲羟戊酸可逆和rac1介导的NADPH氧化酶抑制。结论心肌O-2(-)/ONOO-与心脏手术后院内并发症有较强的独立相关性。术前他汀类药物治疗可通过rac1介导的NADPH氧化酶活性抑制降低心肌O-2（-）和ONOO-。这些发现表明，抑制心肌NADPH氧化酶可能有助于他汀类药物对心脏手术患者的有益作用。阿托伐他汀对心血管高危患者内皮功能、血管和心肌氧化还原状态的影响[J] .中华心血管病杂志，2012;59:60-70)(C) 2012，美国心脏病学会基金会
Objectives The purpose of this study was to evaluate the role of the myocardial redox state in the development of in-hospital complications after cardiac surgery and the effect of statins on the myocardial redox state.Background Statins improve clinical outcome after cardiac surgery, but it is unclear whether they exert their effects by modifying the myocardial redox state.Methods We quantified myocardial superoxide anion (O-2(-)) and peroxynitrite (ONOO-) and their enzymatic sources in samples of the right atrial appendage (RAA) from 303 patients undergoing cardiac surgery who were followed up until discharge, and in 42 patients who were randomized to receive 3-day treatment with atorvastatin 40 mg/d or placebo before surgery. The mechanisms by which atorvastatin modifies myocardial redox state were investigated in 26 RAA samples that were exposed to atorvastatin ex vivo.Results Atrial O-2(-) (derived mainly from nicotinamide adenine dinucleotide phosphate [NADPH] oxidases) and ONOO- were independently associated with increased risk of atrial fibrillation, the need for post-operative inotropic support, and the length of hospital stay. Pre-operative atorvastatin treatment suppressed atrial NADPH oxidase activity and myocardial O-2(-) and ONOO- production. Ex vivo incubation of RAA samples with atorvastatin induced a mevalonate-reversible and Rac1-mediated inhibition of NADPH oxidase.Conclusions There is a strong independent association between myocardial O-2(-)/ONOO- and in-hospital complications after cardiac surgery. Both myocardial O-2(-) and ONOO- are reduced by pre-operative statin treatment, through a Rac1-mediated suppression of NADPH oxidase activity. These findings suggest that inhibition of myocardial NADPH oxidases may contribute to the beneficial effect of statins in patients undergoing cardiac surgery. (Effects of Atorvastatin on Endothelial Function, Vascular and Myocardial Redox State in High Cardiovascular Risk Patients; NCT01013103) (J Am Coll Cardiol 2012; 59: 60-70) (C) 2012 by the American College of Cardiology Foundation