Ischemic Preconditioning Confers Antiapoptotic Protection During Major Hepatectomies Performed Under Combined Inflow and Outflow Exclusion of the Liver. A Randomized Clinical Trial

Extensive experimental studies and a few clinical series have shown that ischemic preconditioning (IPC) attenuates oxidative ischemia/reperfusion (I/R) injuries in liver resections performed under inflow vascular control. Selective hepatic vascular exclusion (SHVE) employed during hepatectomies completely deprives the liver of blood flow, as it entails simultaneous clamping of the portal triad and the main hepatic veins. The aim of the present study was to identify whether IPC can also protect hepatocytes during liver resections performed under SHVE. Patients undergoing major liver resection were randomly assigned to have either only SHVE (control group, n = 43) or SHVE combined with IPC-10 min of ischemia followed by 15 min of reperfusion before SHVE was applied (IPC group, n = 41). The two groups were comparable with regard to age, liver resection volume, blood loss and transfusions, warm ischemic time, and total operative time. In liver remnant biopsies obtained 60 min post-reperfusion, IPC patients had significantly fewer cells stained positive by TUNEL compared to controls (19% +/- A 8% versus 45% +/- A 12%; p < 0.05). Also IPC patients had attenuated hepatocyte necrosis, systemic inflammatory response, and oxidative stress as manifested by lower postoperative peak values of aspartate transaminase, interleukin-6, interleukin-8, and malondialdehyde compared to controls. Morbidity was similar for the two groups, as were duration of intensive care unit stay and extent of total hospital stay. In major hepatectomies performed under SHVE, ischemic preconditioning appears to attenuate apoptotic response of the liver remnant, possibly through alteration of inflammatory and oxidative pathways.