The ischemic liver—do not resuscitate too much

The interest in liver transplantation has focused more attention on the mechanisms of injury during hepatic ischemia, preservation, and reperfusion. Although the human liver has been successfully maintained under hypothermic conditions for up to 10 hours, organ preservation remains the major obstacle to liver transplantation. With tissue ischemia, cell respiration and oxidative phosphorylation cease, with a decline in high‐energy phosphates including adenosine triphosphate (ATP). If oxygen and substrate are made available within a certain period of time, energy stores are regenerated and cells live. However, with irreversible ischemia, ATP stores cannot be regenerated despite the restoration of blood flow, and the cells consequently die. When ATP‐MgCl 2 has been given by intravenous infusion, animal survival has been improved in shock, and renal function and histology have been maintained after renal ischemia. The mechanism responsible for this beneficial effect of ATP‐MgCl 2 has not been defined, but it is generally presumed that ATP preserves sublethally injured cells by enhancing their repair and recovery after ischemic injury. Although reperfusion is necessary to prevent cell death, it is not without hazard. During the period of ischemia, ATP is broken down to adenosine monophosphate, adenosine, inosine, and finally to hypoxanthine, which can be irreversibly converted by xanthine oxidase to xanthine. The introduction of oxygen into this reaction by reperfusion results in the production of the free radicals superoxide (0 2 ) and hydrogen peroxide (H 2 O 2 ), which are mediators of tissue injury, probably by lipid peroxidation. Protection from these oxidative effects can be achieved by dismutation of superoxide to H 2 O 2 by the enzyme superoxide dismutase (SOD) and reduction of H 2 O 2 by catalase.