Remote myocardial injury: the protective role of fluoxetine

Abstract

Aortic cross-clamping-induced ischemia-reperfusion (IR) is an important factor in the development of postoperative acute cardiac injury following abdominal aortic surgery. We investigated the possible anti-oxidant/anti-inflammatory effects of fluoxetine (FLX), which is used widely as a preoperative anxiolytic on cardiac injury induced by IR of the infrarenal abdominal aorta. FLX was administered to IR-performed (60 min of ischemia and 120 min of reperfusion) rats for 3 days, once daily at 20 mg/kg i.p. dosage. Results were compared to control and non-FLX-treated IR-performed rats. Serum creatine kinase (CK) and CK-MB levels, lipid hydroperoxide, thiobarbituric acid reactive substances, and pro-oxidant/anti-oxidant balance levels in the IR group were significantly higher whereas superoxide dismutase activity, glutathione, and ferric reducing/anti-oxidant power levels were lower than for the control. IR also increased myeloperoxidase activity, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 and decreased interleukin-10 levels. FLX decreased CK, CK-MB, lipid hydroperoxide, thiobarbituric acid reactive substances, and pro-oxidant/anti-oxidant balance levels while increasing superoxide dismutase activity, glutathione, and ferric reducing/anti-oxidant power levels. FLX also decreased myeloperoxidase activity, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 levels and increased interleukin-10 levels compared to IR. FLX attenuated the morphological changes associated with cardiac injury. Our study clearly demonstrates that FLX confers protection against aortic IR-induced cardiac injury, tissue leucocyte infiltration, and cellular integrity via its anti-oxidant/anti-inflammatory effects.