Oxidative stress and nitric oxide pathway in adult patients who are candidates for cardiac surgery: patterns and differences

Abstract

Objectives: We investigated whether oxidative stress and the arginine/nitric oxide pathway differ in control subjects and in adult patients who are candidates for the three most common cardiac surgical operations: coronary bypass surgery, aortic valve replacement for calcific non-rheumatic aortic stenosis or mitral valve repair for degenerative mitral insufficiency.

Methods: In this prospective observational study, we studied 165 consecutive patients undergoing surgery from January to June 2011 (coronary bypass surgery, n = 63; aortic valve replacement for calcific non-rheumatic aortic stenosis, n = 51; mitral valve repair for degenerative mitral insufficiency, n = 51). Thirty-three healthy subjects with cardiovascular risk factors similar to surgery patients were also studied (Controls). Oxidative stress (the ratio of reduced and oxidized glutathione and urinary isoprostane), antioxidants (alpha- and gamma tocopherol) and factors involved in nitric oxide synthesis (arginine, symmetric and asymmetric dimethylarginine) were measured before surgery. Analysis of variance general linear models and principal component analysis were used for statistical analysis.

Results: Surgical patients had increased levels of oxidative stress and decreased levels of antioxidants. Increased levels of nitric oxide inhibitor asymmetric dimethylarginine were detected in surgical candidates, suggesting arginine/nitric oxide pathway impairment. Concerning the differences among surgical procedures, higher oxidative stress and a major imbalance of the ratio between substrate and inhibitors of nitric oxide synthesis were evidenced in patients who were candidates for mitral valve repair with respect to coronary bypass surgery patients and patients with calcific non-rheumatic aortic stenosis.

Conclusions: Patients undergoing cardiac surgery have increased oxidative stress and a trend towards an impaired arginine/nitric oxide pathway with respect to Controls. Patients affected by mitral valve regurgitation show more pronounced perturbations in these pathways. The clinical implications of these findings need to be investigated.

Keywords: Aortic valve stenosis; Coronary artery disease; Mitral valve regurgitation; Nitric oxide; Oxidative stress.

Figures

Figure 1:

Oxidative stress markers: glutathione/disulphide glutathione ratio (A) and 8-iso-prostaglandin F2α (B) adjusted means and 95% CI. On the left side: controls and surgical patients (***P < 0.001, Model 3); on the right side: patients grouped by cardiac surgical procedures (##P < 0.01, Model 3, coronary artery bypass surgery or Aortic vs Mitral).

Figure 2:

Antioxidant factors: α-tocopherol (A), γ-tocopherol (B) and glutathione (C) adjusted means and 95% CI. On the left side: controls and surgical patients (***P < 0.001 or **P < 0.01, Model 3); on the right side: patients grouped by cardiac surgical procedures.

Figure 3:

Arginine/nitric oxide (Arg/NO) pathway: endogenous synthesis inhibitor asymmetric dimethylarginine (ADMA) (A), indexes of the Arg/NO metabolic pathway Arg/ADMA ratio (B) and Arg/symmetric dimethylarginine ratio (C) adjusted means and 95% CI. On the left side: controls and surgical patients (**P < 0.01, Model 3); on the right side: patients grouped by cardiac surgical procedures (#P < 0.05, Model 3, coronary artery bypass surgery or Aortic vs Mitral).

Figure 4:

Principal component analysis: location of the four groups (means and SEM) in the plain defined by the two first principal components derived from 10 markers of oxidative balance and the nitric oxide (NO) pathway. The first principal component (horizontal axis) is mainly correlated with antioxidant defences (mostly glutathione), while the second component (vertical axis) is more associated with the arginine (Arg)/NO pathway (mostly Arg and symmetric dimethylarginine).