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 Foundatio
