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J Thorac Cardiovasc Surg 2007;133:696-703
© 2007 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

N-acetylcysteine to ameliorate acute renal injury in a rat cardiopulmonary bypass model

Jiaquan Zhu, MD*, Rong Yin, MD, Hongtao Shao, MD, Guohua Dong, MD, Liguo Luo, MD, Hua Jing, MD

Department of Cardiothoracic Surgery, Jinling Hospital, Clinical Medicine School of Nanjing University, Nanjing, China.

Received for publication July 13, 2006; revisions received August 24, 2006; accepted for publication September 25, 2006.

* Address for reprints: Jiaquan Zhu, MD, Address: Department of Cardiothoracic Surgery, Jinling Hospital, Clinical Medicine School of Nanjing University, 305 E Zhongshan Rd, Nanjing 210002, China (Email: doctor_zhujq{at}yahoo.com.cn).

Objective: Oxidative stress and systemic inflammation response contribute to acute renal injury post cardiac surgery. We hypothesized that administration of the antioxidant N-acetylcysteine would be beneficial to renal function after cardiopulmonary bypass in a rat model.

Methods: Male Sprague–Dawley rats were divided into four groups (each n = 6): sham group, cardiopulmonary bypass group, and two N-acetylcysteine–treated cardiopulmonary bypass groups (bolus doses of 200 and 500 mg/kg in cardiopulmonary bypass prime). Blood samples were collected at the beginning of cardiopulmonary bypass, at the cessation of cardiopulmonary bypass, and at 2 and 12 postoperative hours. The kidneys were harvested at 12 postoperative hours.

Results: Serum creatinine and cystatin C continuously increased in all cardiopulmonary bypass groups (P < .05 within groups). Tubular dilatation, tubular necrosis, and vacuole formation were found in epithelial cells in histomorphologic studies of the cardiopulmonary bypass groups, but N-acetylcysteine significantly reversed these effects (P < .05 between groups). Compared with the sham group, the reduced glutathione hormone content and the superoxide dismutase and catalase activities decreased in the cardiopulmonary bypass groups (P < .01). N-acetylcysteine–treated groups had higher levels of these antioxidants than the untreated bypass group (P < .05). Renal malondialdehyde, tumor necrosis factor {alpha}, and nuclear factor {kappa}B were notably increased in all cardiopulmonary bypass groups relative to the sham group (P < .01), and N-acetylcysteine attenuated these changes dose dependently.

Conclusion: Administration of the antioxidant N-acetylcysteine preserved renal function after cardiopulmonary bypass dose dependently. Furthermore, oxidative stress and systemic inflammation were significantly reduced in the treated animals.

Abbreviations and Acronyms CPB = cardiopulmonary bypass; GSH = reduced glutathione; MDA = malondialdehyde; NAC = N-acetylcysteine; NF-{kappa}B = nuclear factor {kappa}B; SOD = superoxide dismutase; TNF {alpha} = tumor necrosis factor {alpha}




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