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J Thorac Cardiovasc Surg 2003;126:1513-1520
© 2003 The American Association for Thoracic Surgery

Cardiopulmonary support and physiology

N-acetylcysteine prevents reactive oxygen species–mediated myocardial stress in patients undergoing cardiac surgery: Results of a randomized, double-blind, placebo-controlled clinical trial

^a Department of Cardiothoracic Surgery,University of Cologne, Cologne, Germany
^b Department of Anatomy, University of Cologne, Cologne, Germany,
^c Department of Cardiology, University of Cologne, Cologne, Germany
^d Department of Anesthesiology, University of Cologne, Cologne, Germany
^e Department of Medical Statistics, Informatics, and Epidemiology, University of Cologne, Cologne, Germany

Received for publication October 31, 2002; revisions received February 10, 2003; revisions received February 11, 2003; accepted for publication April 11, 2003.

^* Address for reprints: Uwe Mehlhorn, MD, Department of Cardiothoracic Surgery, University of Cologne, Joseph-Stelzmann-Str. 9, 50924 Cologne, Germany
uwe.mehlhorn{at}medizin.uni-koeln.de

OBJECTIVE: Reactive oxygen species have been shown to contribute to myocardial stress in patients undergoing cardiac surgery, as demonstrated by myocardial 8-iso-prostaglandin-F₂ and nitrotyrosine formation. We hypothesized that the reactive oxygen species scavenger N-acetylcysteine attenuates reactive oxygen species–mediated myocardial stress in patients undergoing cardiac surgery.

METHODS: Forty patients undergoing coronary artery surgery (mean age ± SD, 66 ± 9 years; 9 women and 31 men) were randomized to receive either N-acetylcysteine (100 mg/kg into cardiopulmonary bypass prime followed by infusion at 20 mg · kg^-1 · h^-1, n = 20) or placebo (n = 20). Patients and clinical staff were blinded to group assignment. Transmural left ventricular biopsy specimens collected before and at the end of cardiopulmonary bypass were subjected to immunocytochemical staining against 8-iso-prostaglandin-F₂ (primary measure) as an indicator for reactive oxygen species–mediated lipid peroxidation and nitrotyrosine (coprimary measure) as a marker for peroxynitrite-mediated tissue injury. Cardiomyocyte staining was quantitatively determined by using densitometry (in gray units). Global left ventricular function was measured on the basis of fractional area of contraction by using transesophageal echocardiography.

RESULTS: Patient characteristics in both groups were comparable. The change in left ventricular cardiomyocyte staining (end of cardiopulmonary bypass - before cardiopulmonary bypass) differed significantly between groups for both primary measures: 8-iso-prostaglandin-F₂, -1.8 ± 7.5 gray units (mean ± SD, N-acetylcysteine group) versus 5.0 ± 4.1 gray units (placebo group; 95% confidence interval, 2.6-11.0, P = .003); nitrotyrosine, -6.4 ± 10.0 gray units (N-acetylcysteine group) versus 9.2 ± 8.4 gray units (placebo group; 95% confidence interval, 9.4-21.7, P < .001). Hemodynamics and clinical outcomes were comparable in both groups.

CONCLUSIONS: Reactive oxygen species scavenging with N-acetylcysteine attenuates myocardial oxidative stress in the hearts of patients subjected to cardiopulmonary bypass and cardioplegic arrest.

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