Hepatic stress gene expression and ultrastructural features under intermittent Pringle manoeuvre

Background: Intermittent Pringle manoeuvre resul- ted in less blood loss and better preservation of liver function when it was applied for fewer than 120 mi- nutes. The mechanism of better preservation of liver function under intermittent Pringle manoeuvre at molecular level remains unclear. Furthermore, the ultrastructural features in the liver with chronic di- seases under intermittent Pringle manoeuvre have not been studied. The aim of the study is to investigate the expression of stress genes and ultrastructural change of the liver under intermittent Pringle ma- noeuvre. Methods: From July 1995 to February 1998, 131 pa- tients underwent hepatectomy for liver tumours (61 patients without Pringle manoeuvre and 70 patients with intermittent Pringle manoeuvre). Twenty-five patients (15 with Pringle manoeuvre and 10 without Pringle manoeuvre) were included in the study of he- patic stress gene expression during hepatectomy. Twenty-two patients (18 patients with intermittent Pringle manoeuvre and four patients without Pringle manoeuvre) were randomly assigned for electron mi- croscopic examination. Results: For the expression of stress genes, both the heat shock genes (HSP 70A and HSC 70) and acute phase genes (TNF-α and interleukin-6) were detec- ted simultaneously in the patients with or without in- termittent Pringle manoeuvre. The patients under in- termittent Pringle manoeuvre had relatively higher mRNA levels of heat shock gene 70 family, which is related to intracellular repair and protection. Induc- tion of TNF-α and interleukin-6 genes, which con- tributed to ischaemia-reperfusion injury and posto- perative complication, was not found in the patients under intermittent Pringle manoeuvre. Under the e- lectron microscopy, the hepatic ultrastructure was well maintained under intermittent Pringle manoeu- vre whatever the liver status, even when the accumu- lated ischaemic duration was extended to 120 min. Conclusion: Intermittent Pringle manoeuvre induced relatively higher expression of heat shock genes, which are related to intracellular homeostasis, and is consistent with the well maintenance of liver ultra- structure.

Reduction of ischemia reperfusion injury after liver resection and hepatic inflow occlusion by α-lipoic acid in humans

AIM： To evaluate the protective effects of preconditioning by α-lipoic acid （LA） in patients undergoing hepatic resection under inflow occlusion of the liver. METHODS： Twenty-four patients undergoing liver resection for various reasons either received 600 mg LA or NaCI 15 min before transection performed under inflow occlusion of the liver. Blood samples and liver wedge biopsy samples were obtained after opening of the abdomen immediately after inflow occlusion of the liver, and 30 min after the end of inflow occlusion of the liver. RESULTS： Serum levels of aspartate transferase and alanine transferase were reduced at all time points in patients who received LA in comparison to those who received NaCL. This was accompanied by reduced histomorphological features of oncosis. We observed TUNEL-positive hepatocytes in the livers of the untreated patients, especially after 30 min of ischemia. LA attenuated this increase of TUNEL-positive hepatocytes. Under preconditioning with LA, ATP content was significantly enhanced after 30 min of ischemia and after 30 min of reperfusion. CONCLUSION： This is the first report on the potential for LA reducing ischemia/reperfusion injury （IRI） of the liver in humans who were undergoing liver surgery. Beside its simple and rapid application, side effects did not occur. LA might therefore represent a new strategy against hepatic IRI in humans.