Myocardial Redox State Predicts In-Hospital Clinical Outcome After Cardiac Surgery Effects of Short-Term Pre-Operative Statin Treatment

被引：92

作者：

Antoniades, Charalambos ^{[1
,2
]}

Demosthenous, Michael ^{[2
]}

Reilly, Svetlana ^{[1
]}

Margaritis, Marios ^{[1
]}

Zhang, Mei-Hua ^{[1
]}

Antonopoulos, Alexios ^{[2
]}

Marinou, Kyriakoula ^{[3
]}

Nahar, Keshav ^{[1
]}

Jayaram, Raja ^{[1
]}

Tousoulis, Dimitris ^{[2
]}

Bakogiannis, Constantinos ^{[2
]}

Sayeed, Rana ^{[4
]}

Triantafyllou, Costas ^{[5
]}

Koumallos, Nikolaos ^{[5
]}

Psarros, Costas ^{[2
]}

Miliou, Antigoni ^{[2
]}

Stefanadis, Christodoulos ^{[2
]}

Channon, Keith M. ^{[1
]}

Casadei, Barbara ^{[1
]}

机构：

[1] Univ Oxford, John Radcliffe Hosp, Dept Cardiovasc Med, Oxford OX3 9DU, England

[2] Univ Athens, Sch Med, Dept Cardiol 1, GR-11527 Athens, Greece

[3] Univ Athens, Sch Med, Dept Expt Physiol, GR-11527 Athens, Greece

[4] John Radcliffe Hosp, Dept Cardiac Surg, Oxford OX3 9DU, England

[5] Hippokrateion Hosp, Dept Cardiac Surg, Athens, Greece

来源：

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY | 2012年 / 59卷 / 01期

关键词：

atrial fibrillation; cardiac surgery; myocardium; NADPH oxidase; statins; ATRIAL-FIBRILLATION; NAD(P)H OXIDASE; ASSOCIATION;

D O I：

10.1016/j.jacc.2011.08.062

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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

引用

页码：60 / 70

页数：11

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