Protective effect of liver ischemic preconditioning on liver and lung injury induced by hepatic ischemia-reperfusion in the rat

This study evaluates whether preconditioning could modulate the injurious e ffects of tumor necrosis factor (TNF) on liver and lung following hepatic i schemia-reperfusion (I/R) by inhibiting hepatic postischemic TNF release. T he inhibition of hepatic TNF release from Kupffer cells with gadolinium chl oride (GdCl3) previous to ischemia maintained TNF at control levels, attenu ating the increases in transaminases, vascular permeability, and edema asso ciated with hepatic I/R injury; TNF addition reverted this beneficial effec t, indicating the implication of the TNF released mainly from Kupffer cells in hepatic L/R injury. Preconditioning prevented hepatic TNF increases, th us attenuating the liver injury, while TNF addition abolished the benefits of preconditioning. Inhibition of nitric oxide (NO) synthesis abolished the effect of preconditioning, whereas GdCl3 addition avoided the injurious ef fect of NO inhibition. In addition, NO administration before VR offered sim ilar results to those found in preconditioning, while TNF addition abolishe d the benefits of NO. Thus, the effect of preconditioning on TNF release af ter hepatic VR is mediated by NO. Inhibition of hepatic TNF release from Ku pffer cells with GdCl3 prevented both the increase in plasma TNF and the in jurious effect in lung seen after hepatic I/R, and these effects were rever ted with TNF addition. Preconditioning resulting in reduced hepatic TNF lev els prevented the systemic TNF release, thus reducing the lung damage follo wing hepatic I/R, However, TNF addition abolished the protective effect of preconditioning on lung injury. These findings indicate that preconditionin g attenuates hepatic postischemic TNF release from Kupffer cells, thus prob ably reducing the liver and lung injury following hepatic I/R, and that thi s effect of preconditioning is mediated by NO.