VEGF enhances serum levels of HGF and IL-6 in rats following 50 percent partial liver transplantation / 第三军医大学学报

Objective To determine the effects of exogenous VEGF on the serum levels of HGF and IL-6 in rats following partial liver transplantation.Methods Totally 180 SD rats were subjected to 50 percent partial liver transplantation,then each 60 rats were treated either with VEGF,anti-VEGF or normal saline.HGF,IL-6 and hepatic biochemical markers were assessed at 0,12,24,72,168 h after operation.Results In the VEGF group,the serum levels of HGF and IL-6 were significantly increased as compared with those of anti-VEGF group or control group.Blockage of endogenous VEGF led to a marked increase of ALT and AST.Conclusion VEGF can markedly increase the secretion of HGF and IL-6,which may be related to its enhancing liver regeneration and improving liver function.

Pathologic Scoring and Postoperative Liver Function in Canine Partial Liver Transplantation: after Desferrioxamine Exposure / 대한이식학회지

PURPOSE: Liver biopsy plays an important role in the histopathological evaluation of the transplanted liver, but till now pretransplant graft biopsy has limited role in predicting primary non function of the graft. Desferrioxamine (DFO), the iron chelating agent, has been known to be effective in reducing rat liver ischemia-reperfusion injury. We tried desferrioxamine in canine partial liver transplantation, and pathologic scores were compared. METHODS: ~70% partial liver was harvested and reimplanted in same mongrel dog weighing about 25 kg. Desferrioxamine (20 mg/kg) was infused via splenic vein just from the beginning of reperfusion of the partial liver graft (n=5). Serum aspartate aminotransferase (AST) Alkaline phosphatase (ALP), Lactate dehydrogenase (LDH) were checked and compared with the control group (n=5). Morphological liver injury score were compared to the control group. Statistical analysis was done with independent T-test. RESULTS: Total ischemic time was 4 hours and 42 minutes in average. AST level was significantly lower in Desferrioxamine group at 1 hour and 48 hours after reperfusion, (P=0.4) ALP level was significantly lower in desferrioxamine group at 48 hours after reperfusion (P=0.4). LDH level in desferrioxamine group was lower than that of control group but without statistical significance. The pathologic score at 1 hour after reperfusion showed a reduced degree of sinusoidal injury among the DFO group but the difference was not statistically significant. The pathologic score just before harvest of the graft showed no correlation with serum AST, ALP, LDH levels at that time or at 1 hour or 48 hours after reperfusion. Only the pathologic score at 1 hour after reperfusion had significant correlation with the serum LDH levels at 48 hours after reperfusion. CONCLUSION: In canine live donor partial liver transplantation, desferrioxamine infusion just before reperfusion might be an effective way of reducing ischemia-reperfusion injury. And the pathologic grading on samples obtained at 1 hour after reperfusion showed a significant correlation with subsequent liver function

Postoperative Liver Regeneration and Complication In Live Liver Donor after Partial Hepatectomy for Living Donor Liver Transplantation

The safety of donor is the first priority during whole procedure in living donor liver transplantation. We evaluated the short-term results of partial living donor liver transplantation in the view of donor safety. We prospectively evaluated the extent of liver regeneration, the recovery of liver function, and the perioperative complications in 41 live liver donors for partial liver transplantation at our institution. We developed novel personal computer volumetry program for the evaluation of liver regeneration. Serial CAT scan was performed preoperatively, at postoperative day (POD) #7 and POD #30 and liver volume was measure by using volumetry program. The serum level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (T.bil.) was serially monitored. There were 34 males and 7 females. The mean preoperative liver volume was 1320.6 cm3. The remained mean liver volume was 687.8 cm3 after harvest, and increased to 954.4 cm3 (144.6%) at POD #7, and 1169.5 cm3 (81.4%) at POD #30, which was 88.5% of preoperative total liver volume. The serum level of ALT/ AST and T.bil. peaked at POD #1 and declined thereafter, and finally returned to preoperative level at POD #30. The regeneration rate was significantly different by age, type and size of graft according to the donors. Six donors experienced postoperative complications and they were four pleural effusions, one wound infection and one case of bile duct stenosis that was treated by endoscopic nasal biliary drainage. All of them were right lobe donors. In conclusion, the donor liver regenerated up to 88.5% of preoperative volume with full recovery of liver function at POD #30. Right lobe donors suffered more complications and need more meticulous operative and postoperative care than left lobe or left lateral segment donors.

Histologic Study on Reperfusion Liver after the Revascularization through the Portal Vein or Hepatic Artery Following Heterotopic Partial Liver Transplantation in Rats

PURPOSE: The technique of partial liver transplantation from a living donor was developed to expand the donor pool. However such small grafts may not only be functionally inadequate for the recipient, but will also sustain injury characterized by cholestasis and histological features of ischemia after implantation. Damage to partial liver grafts after reperfusion is frequently observed but the mechanism of injury remains unclear. Injury to partial liver grafts may be related to changes in portal blood flow. In this study, we investigated the histologic changes of the reperfusion of livers after revascularization through the portal vein or hepatic artery following heterotopic partial liver transplantation in rats. METHODS: Inbred Lewis partial liver were transplanted to inbred Brown Norway rats heterotopically in three groups. The first group of transplants, Group I (Portal vein group, n=3) was reperfused firstly through the portal vein. The second group, Group II (Hepatic artery group, n=3) was firstly reperfused through the hepatic artery. The third group, Group III (Control, n=1) was sham-operated. After reperfusion, the liver grafts were procured and fixed in formalin. The reperfusion livers were studied using immunohistochemical staining and in-situ RT PCR. RESULTS: In the H&E staining of the reperfusion livers there were no differences between groups I and II. Using immunohistochemical staining of TNF,R, FAS L, caspase 8 and in-situ RT PCR (NOS mRNA, TNF,R mRNA, FAS mRNA), the hepatic artery first reperfusion liver showed more damage than the portal vein first reperfusion liver. TUNEL staing showed severe apoptosis in hepatic artery reperfusion liver. CONCLUSION: The expression of the apoptosis molecular markers was more prominent in the reperfused liver performed with initial revascularization using the hepatic artery, rather than portal vein. These findings may be due to fact that the high oxygen blood in the hepatic artery is stressful to the reperfusion liver. The routinely used portal vein first revascularization technique decrease reperfusion injury to the graft when compared to hepatic artery first revascularization.

The Effect of Lipo-PGE1 on Ischemia-Reperfusion Injury and Endothelin-1 Concentrations After Canine Partial Liver Transplantation / 대한간학회지

BACKGROUND/AIM: The lipo-PGE1, known for being more stable during pulmonary circulation and having more targeting effect, has been reported to inhibit ET-1 induced stellate cell contraction. We assessed the effect of lipo-PGE1 on the change of ET-1 concentration and the relationship between ET-1 concentration and the liver damage. METHODS: Mongrel dogs weighing about 25 kg were divided into a control (n=6) and a lipo-PGE1 (n=6) group. Partial liver allotransplantation was performed. In the lipo-PGE1 group, lipo-PGE1 was slowly infused through splenic venous cannulation during the donor liver harvesting procedure (50 microgram) and continuously infused (60 microgram/day) for 48 hours after reperfusion. The AST, ALP, LDH and ET-1 concentrations were monitored RESULTS: The AST and ALP levels of the lipo-PGE1 group were significantly lower than those of the control group both at 1 hour and 48 hours after reperfusion. The LDH level in the lipo-PGE1 group was lower at 1 hour and 48 hours after reperfusion. But there was no statistical difference between the two groups. The baseline ET-1 concentration of the lipo-PGE1 group was eight times higher than that of the control group. The ET-1 concentration was elevated gradually in the control group. There was no significant difference between the two groups at 48 hours. There was no correlation between ET-1 concentrations and AST, ALP, LDH levels. CONCLUSION: This study demonstrated the hepatoprotective effect of the lipo-PGE1 against ischemia-reperfusion injury in canine partial liver allotransplantation. However, the baseline ET-1 level was eight times higher in the lipo-PGE1 group than that of the control group in spite of the hepatoprotective effects of the lipo-PGE1.

Establishment of Canine Partial Liver Autotransplantation Model and Protective Effect of Prostaglandin I2 on the Ischemia-Reperfusion Injury / 대한이식학회지

BACKGROUND: The pathogenesis of primary non function or delayed graft function after liver transplantation is not yet clearly defined. However it is presumed that these unhappy events most likely attributes to the Kupffer cell-mediated, reperfusion injury aggravating the sinusoidal endothelial cell damage following preformed ischemic insults. Prostaglandin (PG) I2 and its analogues were reported to protect the liver against ischemic injury thereby be efficacious for the use during the preservation of harvested liver. Prevention of platelet aggregation, vasodilation, stabilization of lysosomal membranes, and inhibition of thromboxane generated by platelets may be the attributable biological activities of PGI2. PURPOSES: We designed this experimental study to assess the effect of continuous PGI2 infusion during in situ liver splitting on the bile flow from liver segment during resection and after reimplantation, and to establish our unique autotransplantation model in mongrel dogs before warming-up of living donor partial liver transplantation in the clinic. METHODS: Mongrel dogs weighing 15-25 kg were used after fasting for 12 hours. After endotracheal intubation under monitoring, abdomen was opened through the Chevron incision extending to xiphoid process. Initially, the right hepatic duct was ligated and divided. The common bile duct was divided, the end being cannulated proximally and drained. Basal bile flow was measured for 1 hour as a reference value. The left partial graft including the right medial, quadrate, left medial, left lateral lobe, and the papillary process of caudate lobe was resected en bloc. After cold flushing ex vivo, the harvested segment was immediately reimplanted orthotopically. In PGI2 group, PGI2 50 microgram was slowly infused through splenic venous cannulation. After closing the abdomen, the bile flow was measured continuously. RESULTS: Eleven out of 24 dogs were alive 12 hours after surgery; 5 in PGI2 and 6 in control group. Basal mean bile flow (BF) rate were 2.9 ml/hr/100 gm of liver tissue in control vs. 2.5 ml/hr/100 gm in PGI2 group. This difference did not reach the statistical significance. However, postoperative BF increased significantly in PGI2 group; 0.45 ml/hr/100 gm in contro vs. 1.71 ml/hr/100 gm in PGI2 group (p=0.04). CONCLUSION: Continuous infusion of PGI2 through the splenic vein during the harvest of the liver could mitigate the manipulation injury. The BF reflecting the quality of resected liver segment was relatively well preserved in PGI2 group after canine autotransplantation model. This model is not complicated, and will be useful for the mastery of surgical techniques for the living donor partial liver transplantation in the clinic.

A Rat Model of Heterotopic Partial Liver Transplantation with Mesocaval Shunt / 대한이식학회지

Heterotopic partial liver transplantation(HLT) in the rat is relatively simple method to orthotopic liver transplantation. Addition of mesocaval shunt which diverts almost intestinal blood to systemic circulation provides only splenopancreaticoduodenal blood for the graft. The usefulness of our novel model is first, evaluating the pure effect of pancreaticoduodenal blood to liver regeneration, second, evaluating the contribution of splanchnic viscera to liver reperfusion injury. In the first group (conventional HLT, C-HLT), the thirty percent graft liver was transplanted just below the host liver with whole portal blood input. In the second group(mesocaval shunt added HLT, M-HLT), the superior mesenteric vein was diverted to systemic circulation and portal blood from the spleen-pancreas-duodenum supplied the graft. The graft weight at 2 posttransplant weeks was significantly increased in the C-HLT group compared with the M-HLT group, which suggests pancreatic blood alone is not sufficient to regenerate the partial liver grafts. There was no significant difference in the graft survival between two groups, which implies the influence of intestine to postreperfusion injury is negligible.