The Prospective Randomized Controlled Study Of The Effect Of Ischemic Preconditioning For Hepatic Resection Patients Under Hepatic Blood Inflow Occlusion

Objective To investigate the effect of ischemic preconditioning on patients undergoing hepatic resection under hepatic inflow occlusion and its possible mechanism.Methods A total of 100 unselected patients undergoing hepatic resection were prospectively randomized studied from Jan 2005 to Jan 2008 in our department of hepatobiliary surgery,all patients were randomized using sealed envelopes into two groups:IP group (received one cycle of 5 minutes of ischemia followed by 5 minutes of reperfusion before Pringle's maneuver) and control group(received Pringle's maneuver and no IP given).Liver wedge and Tru-cut biopsy samples were obtained before inflow occlusion and 30min after reperfusion.A part of samples was preserved in the liquid nitrogen;the other was fixed in the 10%liquor formaldehyde,and then embeded with ozocerite. Duration of operation,the amount of intraoperative blood loss,the need and amount of perioperative blood transfusion,the liver function of Postoperative days(POD) 1,3 and 7,postoperative mortality,morbidity and duration of hospitalization were compared between the two groups.Morphologic changes of the liver tissue before and after inflow occlusion were observed between the two groups using the HE staining.Hepatocellular apoptosis after inflow occlusion was evaluated between the two groups by in situ terminal deoxynucleotidyl transferase mediated d-UTP nick end-labeling(TUNEL) assay.Expression of HSP70,HSP32,TNF-αand IL-6 mRNA of the liver tissue before and after inflow occlusion were examined with reverse transcription polymerase chain reaction(RT- PCR).Results The general clinical characteristic between the both groups were comparable.Duration of operation,the amount of intraoperative blood loss and the need and amount of perioperative blood transfusion were similar in both groups(PΚ0.05).Although the levels of alanine transaminase(ALT) and aspartate transaminase (AST)(544.9±398.9 U/L and 585.9±488.4 U/L) of the POD1 in the IP group were lower than the control group(631.4±526.1 U/L and 641.8±514.5 U/L),but there were not statistically significant(P＞0.05).In addition,there were not statistically significant between the two groups in the serum transaminase levels of the POD3 and POD7 and postoperative bilirubin and albumen(P＞0.05).A trend toward shorter hospital stays was observed for the preconditioning group compared with the control group(14±7days versus 13±5 days),but these differences were not pronounced(P＞0.05). Postoperative complications between the control group and IP group were not statistically significant(18%versus 12%;P＞0.05).One of the patients in the control group and none of those in the IP group died while in the hospital(P＞0.05).Hepatic inflow occlusion and reperfusion could induce apoptotic sinusoidal lining cells. Although the number of apoptotic sinusoidal lining cells in the IP group(1.56±1.09) were less than that in the control group(1.93±1.32),but there were not statistically significant(P＞0.05).HSP70 and HSP32 mRNA expression increased after the hepatic inflow occlusion and reperfusion,the differences of the HSP70 mRNA espression were statistically significant(P＜0.05),but the differences of the HSP32 mRNA espression were not statistically significant(P＞0.05).Although the HSP70 and HSP32 mRNA expression in the IP group were higher than that in the control group,but there were not statistically significant(P＞0.05).There was no significant differences in TNF-αand IL-6 mRNA expression when the liver tissue from the before or after occlusion between IP group and control group(P＞0.05).Conclusion The clinical use of IP through 5 minutes of warm ischemia followed by 5 minutes reperfusion does not prevent the remanent liver from ischemia reperfusion injury after hepatectomy under Pringle's maneuver.This maneuver does not improve postoperative liver function and does not reduce morbidity or mortality rates and does not shorten hospitalization stays.The clinical use of IP for hepatic resection patients under hepatic blood inflow occlusion to improve the operative outcome is not currently recommended.