N-acetylcysteine prevents reactive oxygen species-mediated myocardial stress in patients undergoing cardiac surgery: results of a randomized, double-blind, placebo-controlled clinical trial.
OBJECTIVE
Reactive oxygen species have been shown to contribute to myocardial stress in patients undergoing cardiac surgery, as demonstrated by myocardial 8-iso-prostaglandin-F(2)alpha 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-F(2)alpha (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-F(2)alpha, -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.
Tossios
Paschalis
P
Department of Cardiothoracic Surgery, University of Cologne, Germany.
Bloch
Wilhelm
W
Huebner
Astrid
A
Raji
M Reza
MR
Dodos
Fotini
F
Klass
Oliver
O
Suedkamp
Michael
M
Kasper
Stefan-Mario
SM
Hellmich
Martin
M
Mehlhorn
Uwe
U
D000111:Acetylcysteine / Q000008:administration & dosage*; D000368:Aged; D001707:Biopsy, Needle; D002315:Cardiopulmonary Bypass / Q000379:methods*; D016001:Confidence Intervals; D001026:Coronary Artery Bypass / Q000379:methods; D023921:Coronary Stenosis / Q000175:diagnosis / Q000601:surgery; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006334:Heart Function Tests; D006439:Hemodynamics; D006801:Humans; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D007432:Intraoperative Period; D008297:Male; D008875:Middle Aged; D015428:Myocardial Reperfusion Injury / Q000473:pathology* / Q000517:prevention & control*; D011336:Probability; D017382:Reactive Oxygen Species / Q000097:blood / Q000378:metabolism*; D012016:Reference Values; D013312:Stress, Physiological / Q000188:drug therapy / Q000517:prevention & control; D016896:Treatment Outcome
D017382:Reactive Oxygen Species; D000111:Acetylcysteine