Levosimendan protection against kidney ischemia/reperfusion injuries in anesthetized pigs

摘要

The aim of the present study was to examine any possible protective effects of levosimendan in an in vivo pig model of renal ischemia/reperfusion (I/R) injury. In 40 anesthetized pigs, I/R was induced by clamping-reopening the left renal artery. During ischemia levosimendan and Custodiol, alone or in co-administration, were infused in the renal artery. In other pigs, levosimendan was infused after the intrarenal administration of nitric-oxide (NO) synthase blocker Nω-nitro-L-arginine methyl ester (L-NAME) or the mitochondrial ATP-sensitive K+ channel (K_(ATP) channel) inhibitor, 5-hydroxydecanoate (5-HD). Throughout the experiments renal function, apoptosis and tissue peroxidation were examined. In pigs treated with levosimendan peroxidation and apoptotic markers were lower than in animals treated with Custodiol alone. In addition, renal function was better preserved, and antioxidant systems were more activated. All beneficial effects were prevented by L-NAME and 5-HD. In conclusion, levosimendan exerted better protection against renal I/R injuries than Custodiol by mechanisms involving mitochondrial K_(ATP) channels and NO.