N-acetylcysteine Improves Early Cardiac Isograft Function in a Rat Heterotopic Transplantation Model

Abstract

Reactive oxygen species play an important role in the early phase of ischemia-reperfusion injury. N-acetylcysteine (NAC), an antioxidant, has shown protective effects in ischemia-reperfusion injuries in some organ transplantations; however, its roles in cardiac transplantation have not been thoroughly evaluated. Lewis rats were divided into three groups ( n = 8 in each group): sham, control, and NAC group. They were subjected to abdominal heterotopic cardiac transplantation and followed for 24 hours postoperation. For the NAC group, a bolus of NAC (150 mg/kg) was infused at 30 minutes before reperfusion, followed by 20 mg/kg/h for 1 hour; another 150 mg/kg NAC intraperitoneally administered 12 hours after reperfusion. Cardiac function and blood inflammation markers were measured at both 2 and 24 hours after reperfusion. Oxidative stress markers and neutrophil infiltration were evaluated in heart tissue at 24 hours postoperatively. Echocardiography showed that NAC significantly improved the postoperative fractional shortening of isografts ( P < .01), although NAC had no effect on the heart rate. Serum lactate dehydrogenase also indicated a significant decrease in the NAC group at 24 hours posttransplantation ( P = .02) Serum tumor necrosis factor-α and interleukin-1 concentrations which rapidly increased postoperatively were reduced by administration of NAC. In transplanted hearts, the increased malondialdehyde level and myeloperoxidase activity were partially reversed by NAC (both P < .01); NAC also replenished endogenous glutathione. Finally, neutrophil infiltration in isografts was reduced in the NAC group. Recipient treatment with continuous intravenous NAC protected cardiac isografts against posttransplantation ischemia-reperfusion injury, probably through its antioxidant and anti-inflammatory properties.