Blood Cardioplegia with N-Acetylcysteine May Reduce Coronary Endothelial Activation and Myocardial Oxidative Stress
Objectives: The aim of this prospective study was to compare the efficacy of intermittent antegrade blood cardioplegia with or without n-acetylcysteine (NAC) in reducing myocardial oxidative stress and coronary endothelial activation.
Methods: Twenty patients undergoing elective isolated coronary artery bypass graft surgery were randomly assigned to receive intermittent antegrade blood cardioplegia (32°C-34°C) with (NAC group) or without (control group) 300 mg of NAC. For these 2 groups we compared clinical outcome, hemodynamic evolution, systemic plasmatic levels of troponin I, and plasma concentrations of malondialdehyde (MDA) and soluble vascular adhesion molecule 1 (sVCAM-1) from coronary sinus blood samples.
Results: Patient demographic characteristics and operative and postoperative data findings in both groups were similar. There was no hospital mortality. Comparing the plasma levels of MDA 10 min after the aortic cross-clamping and of sVCAM-1 30 min after the aortic cross-clamping period with the levels obtained before the aortic clamping period, we observed increases of both markers, but the increase was significant only in the control group (P = .039 and P = .064 for MDA; P = .004 and P = .064 for sVCAM-1). In both groups there was a significant increase of the systemic serum levels of troponin I compared with the levels observed before cardiopulmonary bypass (P < .001), but the differences between the groups were not significant (P = .570).
Conclusions: Our investigation showed that NAC as an additive to blood cardioplegia in patients undergoing on-pump coronary artery bypass graft surgery may reduce oxidative stress and the resultant coronary endothelial activation.
Aruoma OI, Halliwell B, Hoey BM, et al. 1989. The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. Free Radic Biol Med 6:593-7.nBoldt J, Kumle B, Papsdorf M, et al. 1998. Are circulating adhesion molecules specifically changed in cardiac surgical patients? Ann Thorac Surg 65:608-14.nCakir O, Oruc A, Kaya S, et al. 2004. N-acetylcysteine reduces lung reperfusion injury after deep hypothermia and total circulatory arrest. J Card Surg 19:221-5.nCotgreave IA. 1997. N-acetylcysteine: pharmacological considerations and experimental and clinical applications. Adv Pharmacol 38 205-27.nCroal BL, Hillis GS, Gibson PH, et al. 2006 Relationship between postoperative cardiac troponin I levels and outcome of cardiac surgery. Circulation 114:1468-75.nCuzzocrea S, Mazzon E, Costantino G, et al. 2000. Effects of n-acetylcysteine in a rat model of ischemia and reperfusion injury. Cardiovasc Res 47:537-48.nFischer UM, Cox CS Jr, Allen SJ, et al. 2003. The antioxidant N-acetylcysteine preserves myocardial function and diminishes oxidative stress after cardioplegic arrest. J Thorac Cardiovasc Surg 126:1483-8.nFischer UM, Tossios P, Huebner A, et al. 2004. Myocardial apoptosis prevention by radical scavenging in patients undergoing cardiac surgery. J Thorac Cardiovasc Surg 128:103-8.nGroeneveld AB, Sipkema P. 2000. Interaction of oxyradicals, antioxidants, and nitric oxide during sepsis. Crit Care Med 28:2161-2.nKoramaz I, Pulathan Z, Usta S, et al. 2006. Cardioprotective effect of cold-blood cardioplegia enriched with N-acetylcysteine during coronary artery bypass grafting. Ann Thorac Surg 81:613-8.nLaude K, Thuillez C, Richard V. 2001. Coronary endothelial dysfunction after ischemia and reperfusion: a new therapeutic target? Braz J Med Biol Res 34:1-7.nMoukarbel GV, Ayoub CM, Abchee AB. 2004. Pharmacological therapy for myocardial reperfusion injury. Curr Opin Pharmacol 4:147-53.nNesher N, Alghamdi AA, Singh SK, et al. 2008. Troponin after cardiac surgery: a predictor or a phenomenon? Ann Thorac Surg 85:1348-54.nPapaharalambus CA, Griendling KK. 2007. Basic mechanisms of oxidative stress and reactive oxygen species in cardiovascular injury. Trends Cardiovasc Med 17:48-54.nPostadzhiyan AS, Tzontcheva AV, Kehayov I, et al. 2008. Circulating soluble adhesion molecules ICAM-1 and VCAM-1 and their association with clinical outcome, troponin T and C-reactive protein in patients with acute coronary syndromes. Clin Biochem 41:126-33.nRodrigues AJ, Evora PR, Schaff HV. 2004. Protective effect of N-acetylcysteine against oxygen radical-mediated coronary artery injury. Braz J Med Biol Res 37:1215-24.nSochman J, Vrbska J, Musilova B, et al. 1996. Infarct size limitation: acute N-acetylcysteine defense (ISLAND trial): preliminary analysis and report after the first 30 patients. Clin Cardiol 19:94-100.nvan Klaveren RJ, Dinsdale D, Pype JL, et al. 1997. N-acetylcysteine does not protect against type II cell injury after prolonged exposure to hyperoxia in rats. Am J Physiol 273:L548-55.nVento AE, Nemlander A, Aittomaki J, et al. 2003. N-acetylcysteine as an additive to crystalloid cardioplegia increased oxidative stress capacity in CABG patients. Scand Cardiovasc J 37:349-55.nZafarullah M, Li WQ, Sylvester J, et al. 2003. Molecular mechanisms of N-acetylcysteine actions. Cell Mol Life Sci 60:6-20.n
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