Ischemic preconditioning confers antiapoptotic protection during major hepatectomies performed under combined inflow and outflow exclusion of the liver. A randomized clinical trial.

BACKGROUND: 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. METHODS: 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). RESULTS: 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% +/- 8% versus 45% +/- 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. CONCLUSIONS: 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.

Effects of hepatovenous back flow on ischemic- reperfusion injuries in liver resections with the pringle maneuver.

BACKGROUND: Experimental findings have demonstrated a beneficial role of retrograde blood flow from hepatic veins that takes place during the Pringle maneuver in liver resections. The cytoprotective effect of hepatovenous back-perfusion has not been evaluated in humans. A randomized prospective study was designed to compare the response of liver cells to ischemic-reperfusion injury during the application of two different ischemic procedures: inflow versus inflow plus outflow vascular occlusion of the liver. STUDY DESIGN: Forty patients were randomly allocated to undergo liver resection using the continuous Pringle maneuver (n = 20) or inflow plus outflow vascular occlusion of the liver by selective hepatic vascular exclusion (n = 20). Liver function was assessed on postoperative days 1 to 6. Response of liver cells to I/R injury was evaluated by measuring interleukins IL-6 and IL-8 at 3, 12, 24, and 48 hours after reperfusion. Oxidative stress was assessed by measuring malondialdehyde levels. RESULTS: Both groups were comparable regarding ischemic time, operative time, and extent of liver resection. Patients in whom retrograde blood flow to the liver took place during the Pringle maneuver showed better liver function postoperatively and less severe hepatic I/R injuries compared with those undergoing liver resection using both inflow and outflow vascular occlusion. Oxidative stress was significantly lower in the Pringle maneuver group compared with the inflow plus outflow vascular occlusion group (mean [+/- SD] malondialdehyde 8 +/- 2.1 micromol/L in the Pringle group versus 14.7 +/- 1.8 micromol/L in the selective hepatic vascular exclusion group 30 min after reperfusion, p < 0.01). CONCLUSIONS: Back perfusion via hepatic veins contributes to attenuation of I/R damage during the Pringle maneuver and should be preferred if possible during liver resection.