The effects of levosimendan on acute renal injury in an experimental abdominal sepsis model

Objectives: Sepsis is the leading cause of death which is encountered frequently in intensive care units and may cause systemic complications which leads to multiple organ failure. It is shown as the most important cause of acute renal failure. In recent years, new and specific methods has emerged to show acute renal damage like cystatin C and neutrophil gelatinase associated lipocalin (NGAL) levels..We intend to investigate the effects of Levosimendan on kidneys by NGAL levels in rats which are experimentally induced polimicrobial sepsis by cecal ligation and perforation model.Material and Methods: After approval by the Ethics Committee of Animal Experiments in Dokuz Eylul University Faculty of Medicine, Wistar rats, weighing 250-300 gr, were divided into three groups: sham group underwent laparotomy (n=6); sepsis group that had abdominal sepsis induced by cecal ligation and perforation (CLP) method (n=7); sepsis+levosimendan group, after repeating same procedures as in sepsis group, administration of 12 mg/kg bolus dose of levosimendan in 10 min, then 0.2 µg/kg/min levosimendan infusion for 110 minutes (n=7). Mean arterial pressures (MAP) were recorded at 0., 10., 30., 60. and 120. minutes in all groups. NGAL, BUN and creatinine levels in blood samples and malondialdehyde (MDA) activities in kidney tissue were measured. In addition, the renal tissue was also examined histomorphologically.Results: There was no significant difference between baseline MAP values of the groups. MAP in 10th, 30th, 60th min were significantly decreased in sepsis group compared to sham group (p=0.022, p=0.035, p=0.035), while a significant decrease has been observed in 10th and 30th min in sepsis+levosimendan group (p=0.008, p=0.008). NGAL levels were significantly increased in sepsis group compared with sham and sepsis+levosimendan group (p=0.003, p=0.009). NGAL levels of sham group were significantly lower than in the sepsis+levosimendan group (p=0.007). There were no significant difference between BUN and serum creatinine values. MDA levels also did not differ significantly between the groups. Renal histological damage scoring of groups were scored separately as infiltration of mononuclear leukocytes (MNHI), erythrocyte extravasation-vasodilatation (VASO), tubulorinterstitial injury (TUBUL) and renal corpuscle - glomerular injury (GLM). Scores in the sham group were found significantly lower compared with sepsis group (p=0.002, p=0.004, p=0.001, p=0.004) and sepsis+levosimendan group (p=0.004, p=0.003, p=0.001, p=0.001). MNL score was significantly lower in sepsis+levosimendan group (p=0.002) compared with sepsis group, while other parameters were not different.Conclusions: As a result, NGAL appears to be more specific and sensitive parameter than BUN-creatinin and MDA in determination of renal injury occuring in the early stages of sepsis. We concluded that Levosimendan might reduce serious renal damage in sepsis without causing significant hemodynamic response.Key Words: Experimental, Abdominal Sepsis, Levosimendan, NGAL, Acute Renal Injury