Urokinase perfusion prevents intrahepatic ischemic-type biliary lesion in donor livers

AIM： To evaluate whether urokinase perfusion of non-heart-beating cadaveric donor livers reduces the incidence of intrahepatic ischemic-type biliary lesions （IITBLs）. METHODS： A prospective study was conducted to investigate potential microthrombosis in biliary microcirculation when non-heart-beating cadaveric livers were under warm or cold ischemic conditions. The experimental group included 140 patients who underwent liver transplantation during the period of January 2006 to December 2007, and survived for more than 1 year. The control group included 220 patients who received liver transplantation between July 1999 and December 2005 and survived for more than 1 year. In the experimental group, the arterial system of the donor liver was perfused twice with urokinase during cold perfusion and after trimming of the donor liver. The incidence of IITBLs was compared between the two groups. RESULTS： In the control group, the incidence of IITBLs was 5.9% （13/220 cases） after 3-11 mo of transplantation. In the experimental group, two recipients （1.4%） developed IITBLs at 3 and 6 mo after transplantation, respectively. The difference in the incidence between the two groups was statistically significant （P 〈 0.05）. CONCLUSION： Double from non-heart-beating perfusion of cadaveric livers donors with urokinase may reduce the incidence of IITBLs.

Effects of different periods of renal ischemia on liver as a remote organ

AIM:To assess the hepatic changes after induction of different periods of renal ischemia. METHODS:Rats were subjected to either sham operation or ischemia (30,45 and 60 min) followed by 60 min reperfusion. Liver and renal functional indices were measured. Hepatic glutathione (GSH) and ferric reducing antioxidant power levels and the concentration of interleukin (IL)-10 and tumor necrosis factor (TNF-α) were evaluated. Portions of liver and kidney tissues were fixed for histological evaluation. RESULTS:Forty-five minutes renal ischemia followed by 60 min reperfusion caused significant changes in liver structure and a significant reduction in renalfunction. These rats showed a significant decrease in liver GSH,as well as a significant increase in TNF-α and IL-10 concentrations. These results demonstrated that renal ischemia caused changes in liver histology,function,oxidative stress and inflammatory status,which led to a reduction in hepatic antioxidant capacity. With 30 min ischemia,the magnitude of these changes was less than those with 45 or 60 min ischemia.CONCLUSION:A minimum of 45 min ischemia is needed to study the effects of renal injury on the liver as a remote organ.

Role of adhesion molecules and dendritic cells in rat hepatic/renal ischemia-reperfusion injury and anti-adhesive intervention with anti-P-selectin lectin-EGF domain monoclonal antibody

AIM: To investigate the role of P-selectin, intercellular adhesion molecule-1 (ICAM-1) and dendritic cells (DCs)in liver/kidney of rats with hepatic/renal ischemiareperfusion injury and the preventive effect of anti-Pselectin lectin-EGF domain monoclonal antibody (anti-PsLEGFmAb) on the injury.METHODS: Rat models of hepatic and renal ischemiareperfusion were established. The rats were then divided into two groups, one group treated with anti-PsL-EGFmAb(n = 20) and control treated with saline (n = 20). Both groups were subdivided into four groups according to reperfusion time (1, 3, 6 and 24 h). The sham-operated group (n = 5) served as a control group. DCs were observed by the microscopic image method, while P-selectin and ICAM-1 were analyzed by immunohistochemistry.RESULTS: P-selectin increased significantly in hepatic sinusoidal endothelial cells and renal tubular epithelial cells 1 h after ischemia-reperfusion, and the expression of ICAM-1 was up-regulated in hepatic sinusoid and renal vessels after 6 h. CD1a+CD80+DCs gradually increased in hepatic sinusoidal endothelium and renal tubules and interstitium 1 h after ischemia-reperfusion, and there was the most number of DCs in 24-h group. The localization of DCs was associated with rat hepatic/renal function.These changes became less significant in rats treated with anti-PsL-EGFmAb.CONCLUSION: DCs play an important role in immune pathogenesis of hepatic/renal ischemia-reperfusion injury.Anti-PsL-EGFmAb may regulate and inhibit local DC immigration and accumulation in liver/kidney.

Nigella sativa relieves the deleterious effects of ischemia reperfusion injury on liver

AIM: To determine whether Nigella sativa prevents hepatic ischemia-reperfusion injury to the liver. METHODS: Thirty rats were divided into three groups as sham (Group 1), control (Group 2), and Nigella sati-va (NS) treatment group (Group 3). All rats underwent hepatic ischemia for 45 min followed by 60 min period of reperfusion. Rats were intraperitoneally infused with only 0.9% saline solution in group 2. Rats in group 3 received NS (0.2 mL/kg) intraperitoneally, before isch-emia and before reperfusion. Blood samples and liver tissues were harvested from the rats, and then the rats were sacrifi ced. Serum aspartate aminotransfera-se (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were determined. Total antioxidant capacity (TAC), catalase (CAT), total oxida-tive status (TOS), oxidative stress index (OSI) and my-eloperoxidase (MPO) in hepatic tissue were measured. Also liver tissue histopathology was evaluated by light microscopy. RESULTS: The levels of liver enzymes in group 3 weresignifi cantly lower than those in the group 2. TAC in liver tissue was significantly higher in group 3 than in group 2. TOS, OSI and MPO in hepatic tissue were signifi cantly lower in group 3 than the group 2. Histo-logical tissue damage was milder in the NS treatment group than that in the control group. CONCLUSION: Our results suggest that Nigella sa-tiva treatment protects the rat liver against to hepatic ischemia-reperfusion injury.

Reduced antioxidant level and increased oxidative damage in intact liver lobes during ischaemia-reperfusion

AIM： To determine whether increased blood flow of the liver can cause oxidative stress and hepatocyte damage, and to elaborate methods suitable for measuring the antioxidant defence during hepatic surgery on rat model.METHODS： In nembutal narcosis, the left lateral and the medial lobes of the liver were clipped for 45 rain to make the total blood supply flow through the other lobes. Total antioxidant status, glutathione peroxidase and superoxide dysmutase activity, as well as the concentrations of diene conjugates and free sulphydril groups, H-donating ability and reducing power of the liver samples were determined. Chemiluminescent intensity of the liver was also measured. Metal ions （Al, Ca, Cu, Fe, Mg, Mn, Zn） and P and S concentrations of the liver were determined with an inductively coupled plasma optical emission spectrometer and Se content was measured by cathodic stripping voltammetry.RESULTS： Glutathione peroxidase and superoxide dysmutase activities of the liver decreased significantly in the hyperemia group compared to those observed in the sham operated group. The level of total antioxidant status was also significantly lower in the hyperemia group. H-donating ability, reducing power and free sulphydril group concentration showed the same tendency. A significant correlation （P〈0.05） was found between the changes in non-specific antioxidant activities. This pointed to simultaneous activity of the antioxidant defence system. Al, Cu, Mn, Zn, and S were lower in the hyperemia group than in the sham operated group when the levels of Ca, Fe, Mg, Se and P ions were higher during hyperemia.CONCLUSION： Oxidative stress is one of the main factors for the injury of intact liver lobes during ischaemia-reperfusion.

Gender differences in hepatic ischemic reperfusion injury in rats are associated with endothelial cell nitric oxide synthase-derived nitric oxide

AIM: This study was designed to examine the hypothesis that gender differences in I/R injury are associated withendothelial cell nitric oxide synthase (eNOS)-derived nitric oxide (NO).METHODS: Wistar rats were randomized into seven experimental groups (12 animals per group). Except for the sham operated groups, all rats were subjected to total liver ischemia for 40 min followed by reperfusion. All experimental groups received different treatments 45 min before the laparotomy. For each group, half of the animals (six) were used to investigate the survival; blood samples and liver tissues were obtained in the remaining six animals after 3 h of reperfusion to assess serum NO, alanine aminotransferase (ALT) and TNF-α levels, liver tissuemalondialdehyde (MDA) content, and severity of hepatic I/R injury.RESULTS: Basal serum NO levels in female sham operated (FS) group were nearly 1.5-fold of male sham operated (MS) group (66.7±11.0 μmol/L vs 45.3±10.1μmol/L, P＜0.01). Although serum NO levels decreased significantly after hepatic I/R (P＜0.01, vs sham operated groups), they were still significantly higher in female rat (F) group than in male rat (M) group (47.8±8.6 μmol/L vs 23.8±4.7 μmol/L, P＜0.01). Serum ALT and TNF-α levels, and liver tissue MDA content were significantly lower in F group than in M group (370.5±46.4 U/L, 0.99±0.11 μg/L and 0.57±0.10 μmol/g vs668.7±78.7 U/L, 1.71±0.18 μg/Land 0.86±0.11 μmol/g, respectively, P＜0.01). I/R induced significant injury to the liver both in M and F groups (P＜0.01 vs sham operated groups). But the degree of hepatocyte injury was significantly milder in F group than in M group (P＜0.05 and P＜0.01). The median survival time was six days in F group and one day in M group. The overall survival rate was significantly higher in F group than in M group (P＜0.05). When compared with male rats pretreated with saline (M group), pretreatment of male rats with 17-β- estradiol (E2) (M+E2 group) significantly increased serum NO levels and significantly decreased serum ALT and TNF-α levels, and liver tissue MDA content after I/R (P＜0.01).The degree of hepatocyte injury was significantly decreased and the overall survival rate was significantly improved in M+E2 group than in M group (P＜0.01 and P＜0.05). TheNOS inhibitor Nw-nitro-L-arginine methyl ester (L-NAME) treatment could completely abolish the protective effects of estrogen in both male and female rats. CONCLUSION: The protective effects afforded to female rats subjected to hepatic I/R are associated with eNOSderived NO.

Heme oxygenase-1 alleviates ischemia/reperfusion injury in aged liver

AIM: To investigate if ischemia/reperfusion (I/R) injury in aged liver could be alleviated by heme oxygenase-1 (HO-1).METHODS: Three groups of SD rats (16 mo old) were studied. Group 1: control donors received physiological saline 24 h before their livers were harvested; group 2: donors were pretreated with hemih 24 h before their livers were harvested; and group 3: donors received hemin 24 h before their livers were harvested and zinc protoporphyrin (ZnPP,HO-1 inhibitor) was given to recipients at reperfusion. The harvested livers were stored in University of Wisconsin solution (4 ℃) for 6 h, and then transplanted to syngeneic rats. Serum glutamic oxaloacetic transaminase (SGOT),apoptotic cells, and apoptotic gene were measured 3, 6,12, 24, 48 h after reperfusion. We measured the apoptotic index by TUNEL, determined the expression of antiapoptotic Bcl-2 and proapoptotic (caspase-3) gene products by Western blot.RESULTS: After 3, 6, 12, 24, and 48 h of reperfusion, the SGOT levels (584.4±85.8 u/L, 999.2±125.2 u/L, 423.4±161.3u/L, 257.8±95.8 u/L, and 122.4±26.4 u/L) in hemin group were significantly (all P＜0.05) lower than those in saline group (1082.2±101.2 u/L, 1775.2±328.3 u/L, 840.4±137.8 u/L,448.6±74.3 u/L, and 306.2±49.3 u/L). Liver HO-1 enzymatic activity correlated with beneficial effects of hemin and deleterious effects of adjunctive ZnPP treatment. Markedly less apoptotic (TUNEL+) liver cells 3, 6, 12, 24, and 48 h after reperfusion (5.16±0.73, 10.2±0.67, 9.28±0.78, 7.14±1.12,and 4.78±0.65) (P＜0.05) could be detected in hemin liver grafts, as compared to controls (7.82±1.05, 15.94±1.82,11.67±1.59, 8.28±1.09, and 6.36±0.67). We detected the increased levels of Bcl-2 (1.5-fold) expression and compared with saline controls. These differences were most pronounced at 12 h after transplantation. In contrast, an active form of proapoptotic caspase-3 (p20) protein was found to be 2.9-fold lower at 24 h in hemin-pretreated group, as compared to saline liver transplant controls.CONCLUSION: HO-1 overexpression can provide potent protection against cold I/R injury. This effect depends, at least in part, on HO-1-mediated inhibition of antiapoptotic mechanism.

Histological and biochemical alterations in early-stage lobar ischemia-reperfusion in rat liver

AIM： To investigate the structural and biochemical changes in the early stage of reperfusion in the rat livers exposed to lobar ischemia-reperfusion （IR）. METHODS： The median and left lobes of the liver were subjected to 60 min ischemia followed by 5, 10, 30, 45, 60 and 120 min reperfusion. Blood samples were taken at different time intervals to test enzyme activities and biochemical alterations induced by reperfusion. At the end of each reperfusion period, the animals were killed by euthanasia and tissue samples were taken for histological examination and immunohistochemistry. RESULTS： Cell vacuolation, bleb formation and focal hepatitis were the most important changes occur during ischemia. While some changes including bleb formation were removed during reperfusion, other alterations including portal hepatitis, inflammation and the induction of apoptosis were seen during this stage. The occurrence of apoptosis, as demonstrated by apoptotic cells and bodies, was the most important histological change during reperfusion. The severity of apoptosis was dependent on the time of reperfusion, and by increasing the time of reperfusion, the numbers of apoptotic bodies was significantly enhanced. The amounts of lactate dehydrogenase, alanine aminotransferase, aspartate aminotransfrase, creatinine and urea were significantly increased in serum obtained from animals exposed to hepatic IR. CONCLUSION： Inflammation and subsequent apoptotic cell death were the most important changes in early-stage hepatic reperfusion injury, and the number of apoptotic bodies increased with time of reperfusion.

Mild hypothermia protects liver against ischemia and reperfusion injury

AIM: To determine whether mild hypothermia could protect liver against ischemia and reperfusion injury in pigs. METHODS: Twenty-four healthy pigs were randomly divided into normothermia, mild hypothermia and normal control groups. The experimental procedure consisted of temporary interruption of blood flow to total hepatic lobe for different lengths of time and subsequent reperfusion. Hepatic tissue oxygen pressure (PtiO2) and aspartate aminotransferase (AST) values were evaluated, and ultrastructural analysis was carried out for all samples. RESULTS: Serum AST was significantly lower, and hepatic PtiO2 values were significantly higher in the mild hypothermia group than in the normothermia group during liver ischemia-reperfusion periods (P= 0.032, P= 0.028). Meanwhile, the histopathologic injury of liver induced by ischemia-reperfusion was significantly improved in the mild hypothermia group, compared with that in the normothermia group. CONCLUSION: Mild hypothermia can protect the liver from ischemia-reperfusion injury in pigs.

Identification of differentially expressed genes after partial rat liver ischemia/reperfusion by suppression subtractive hybridization

AIM: To identify potential diagnostic target genes in early reperfusion periods following warm liver ischemia before irreversible liver damage occurs. METHODS: We used two strategies (SSH suppression subtractive hybridization and hybridization of cDNA arrays) to determine early changes in gene expression profiles in a rat model of partial WI/R, comparing postischemic and adjacent nonischemic liver lobes. Differential gene expression was verified (WI/R; 1 h/2 h) and analyzed in more detail after warm ischemia (1 h) in a reperfusion time kinetics (0, 1, 2 and 6 h) and compared to untreated livers by Northern blot hybridizations. Protein expression was examined on Western blots and by immunohistochemistry for four differentially expressed target genes (Hsp70, Hsp27, Gadd45a and IL-1rI). RESULTS: Thirty-two individual WI/R target genes showing altered RNA levels after confirmation by Northern blot analyzes were identified. Among them, six functionally uncharacteristic expressed sequences and 26 known genes (12 induced in postischemic liver lobes, 14 with higher transcriptional expression in adjacent nonischemic liver lobes). Functional categories of the verified marker genes indicate on the one hand cellular stress and tissue damage but otherwise activation of protective cellular reactions (AP-1 transcription factors, apoptosis related genes, heat shock genes). In order to assign the transcriptional status to the biological relevant protein level we demonstrated that Hsp70, Hsp27, Gadd45a and IL-1rI were clearly up-regulated comparing postischemic and untreated rat livers, suggesting their involvement in the WI/R context. CONCLUSION: This study unveils a WI/R response gene set that will help to explore molecular pathways involved in the tissue damage after WI/R. In addition, these genes especially Hsp70 and Gadd45a might represent promising new candidates indicating WI/R liver damage.

Evaluation of CMU-1 preservation solutions using an isolated perfused rat liver model

AIM: CMU-1 is a new preservation solution with a low potassium concentration as well as low viscosity that is highly effective in reducing preservation injury. The purpose of this experiment is to compare the protective effect of CMU-1 solution with that of UW during cold preservation and normothermic reperfusion. METHODS: Wistar rats were divided into two groups according to different preservation solution: CMU-1 group and UW group. After 6, 12 and 24 h cold storage of rat liver in different preservation solutions, the isolated perfused rat liver model was applied to reperfuse the liver for 120 min normothermically (37 癈) with Krebs-Henseleit solution, meanwhile the pH value of the preservation solution was measured. The perfusate was sampled for the evaluation of alanine aminotransferase (ALT) and lactate dehydrogenase (LDH). At the end of the reperfusion, all of the bile product was collected, energy metabolic substrate and histological examination were performed. RESULTS: After preserving for 6 h, pH value of both groups did not change; after 12 h, both decreased but with no significant difference. After 24 h, pH value in UW solution group significantly decreased. The total adenine nucleotides level and AEC in liver tissue decreased with preservation time, but they were higher in CMU-1 group. And the amount of bile product after perfusion for 120 min in CMU-1 group was much more than that in UW group. However, there were no significant differences in ALT and LDH levels between two groups. Histology showed no difference. CONCLUSION: The preservation effect of CMU-1 solution is similar with that of UW solution. However, CMU-1 solution shows some advantages over UW solution in energy metabolism, preventing intracellular acidosis and bile product.

EXPERIMENTAL STUDY ON ISCHEMIA AND REPERFUSION INJURY OF RAT LIVER AND EFFECTS OF LIGUSTRAZINE AND SALVIA COMPOUND

The present study was to investigate changes of free radicals in the whole rat liver, changes of ATP levels of hepatic cells, ultrastructural changes in hepatic tissue during ischemia and reperfusion in rats and the effects of ligustrazine and salvia compound. The results indicated that : 1 ) the free radical levels increased by 8. 3-fold and 9.0-fold in the groups with 30 and 60 min ischemia after 40 min reperfusion, as compared with the group with ischemia only (P<0.01, P<0.01, respectively). 2) The levels of ATP returned to normal in the group with 30 min ischemia after reperfusion for 40 min and 3 d , remained low in the group with 90 min ischemia and fell again after a mild increase in the group with 60 min ischemia. 3) The hepatic and endothelial cell damage after ischemia became more severe after reperfusion, as revealed by electron microscopy. The presenet study also showed that ligustrazine and salvia compound have protective effects against reperfusion injury. They can be used to scavenge free radicals, improve hepatic microcirculation and alleviate hepatic and endothelial cell damage.

Japanese herbal medicine, Saiko-keishi-to, prevents gut ischemia/reperfusion-induced liver injury in rats via nitric oxide

AIM:To determine whether Saiko-keishi-to(TJ-10),a Japanese herbal medicine,could protect liver injury induced by gut ischemia/reperfusion(I/R),and to investigate the role of NO. METHODS:Male Wistar rats were exposed to 30-min gut isohemia followed by 60 min of reperfusion.Intravital microscopy was used to monitor leukocyte recruitment.Plasma tumor necrosis factor(TNF)levels and alanine aminotransferase (ALT)activities were measured.TJ-10 1 g/(kg.d)was intragastrically administered to rats for 7 d.A NO synthase inhibitor was administered. RESULTS:In control rats,gut I/R elicited increases in the number of stationary leukocytes,and plasma TNF levels and ALT activities were mitigated by pretreatment with TJ-10.Pretreatment with the NO synthase inhibitor diminished the protective effects of TJ-10 on leukostasis in the liver,and the increase of plasma TNF levels and ALT activities.Pretreatment with TJ-10 increased plasma nitrite/nitrate levels. CONCLUSION:TJ-10 attenuates the gut I/R-induced hepatic microvascular dysfunction and sequential hepatocellular injury via enhancement of NO production.

Matrix metalloproteinase-9:A deleterious link between hepatic ischemia-reperfusion and colorectal cancer

Despite the advent of improved surgical techniques and the development of cytotoxic chemotherapeutic agents useful for the treatment of colorectal cancer,the primary clinical challenge remains that of preventing and combating metastatic spread.Surgical resection is the best treatment for colorectal metastases isolated to the liver.However,in rodent models,the hepatic ischemia-reperfusion(I/R) applied during the surgery accelerates the outgrowth of implanted tumors.Among the adverse effects of I/R on cellular function,several studies have demonstrated an over expression of the matrix metalloproteinase-9(MMP-9) in the ischemic liver.Since several studies showed high local levels of expression and activity of this proteolytic enzyme in the primary colorectal adenocarcinoma,the role of MMP-9 might be considered as a potential common mediator,favoring both growth of local tumor and the dissemination of colorectal carcinoma metastases.

Herbal cardiotonic pills prevent gut ischemia/reperfusion-induced hepatic microvascular dysfunction in rats fed ethanol chronically

AIM: Cardiotonic Pill (CP), an oral herbal medicine that includes Danshen (Salviae Miltiorrhizae), Panax notoginseny and Dyroblanops aromatica gaettn, has been clinically used for vascular diseases such as occlusive vasculitis, coronary diseases, atherosclerosis, and cerebral infarction. The main component, Salviae Miltiorrhizae, has been reported to prevent cerebral and intestinal reperfusion injury. However, little is known about the effect of CP on hepatic microcirculation. Thus, this study aimed to determine whether CP could affect hepatic microvascular dysfunction elicited by gut ischemia/ reperfusion (I/R) in rats fed ethanol chronically. METHODS: Male Wistar rats were pair-fed with a liquid diet containing ethanol or isocaloric control diet for 6 wk. After laparotomy, one lobe of the liver was examined through an inverted intravital microscope. The rats were exposed to 30 min of gut ischemia followed by 60 min of reperfusion. Rhodamine-6G-labeled leukocytes in the sinusoids were observed 90 min after the onset of superior mesenteric artery occlusion. Plasma tumor necrosis factor (TNF)-α and endotoxin levels were measured 1 h after the onset of reperfusion. Plasma alanine aminotransferase (ALT) activities were measured 6 h after the onset of reperfusion. In another set of experiments, CP (0.8 g/kg, intragastrically) was administered 1 and 24 h before the onset of ischemia. RESULTS: In control rats, gut I/R elicited increases in the number of stationary leukocytes, and plasma TNF-α and endotoxin levels and plasma ALT activities. These changes were mitigated by pretreatment with CP. In ethanol-fed rats, the gut I/R-induced increases in the number of stationary leukocytes, plasma endotoxin levels and ALT activities were enhanced. Pretreatment with CP attenuated the enhancement of gut I/R-induced responses by chronic ethanol consumption. CONCLUSION: These results suggest that CP prevents the gut I/R-induced hepatic microvascular dysfunction and hepatocellular injury. A reduction of inflammatory responses such as TNF-α production via reduction of blood endotoxin levels appears to be involved in the mechanisms. Chronic ethanol consumption enhances gut I/R-induced hepatic microvascular and hepatocellular injury. CP also attenuates an enhancement of gut I/R-induced responses by chronic ethanol consumption via the reduction of blood endotoxin levels.

Progression of hepatic hyperperfusion disorders revealed during follow-up CT scan of digestive system neoplasm

Objective： The aim of this study was to investigate progression of hepatic hyperperfusion disorders revealed during follow-up contrast material-enhanced multi-slice spiral computed tomography （MSCT） scan of digestive system neoplasm. Methods： Three-phase contrast material-enhanced MSCT were performed during the follow-up in patients with digestive system malignant tumor confirmed histologically. The progression of hepatic hyperperfusion disorders revealed on contrast material-enhanced CT image were investigated at the 2 years follow-up with approximately 6 months interval. Results： The hepatic hyperperfusion disorders were showed in 39 patients on follow-up contrast material-enhanced MSCT scans. Among the 39 patients, initial hyperperfusion disorders were revealed in 6 （15.38%）, 26 （66.67%）, and 7 （17.95%） patients in 6, 12, and 18 months during follow-up respectively. The initial hyperperfusion disorders revealed in 12 months were more frequent than those revealed in 6 months （X2 = 14.82, P 〈 0.05） and 18 months （X2 = 15.02, P 〈 0.05）. Among the 39 patients, the hyperperfusion disorders progressed into liver metastasis based on typical CT findings in 37 （94.87%） patients, and were not obvious changes in 2 （5.13%） patients. Among the 37 patients, the hyperperfusion disorders progressed into metastasis in 10 （25.64%） patients in 6 months after the hyperperfusion disorders were revealed, and in 27（69.23%） patients in 12 months. The hyperperfusion disorders developing into metastasis were more in 12 months than those in 6 months （X2= 14.98, P 〈 0.05）. Conclusion： Most hepatic hyperperfusion disorders revealed at the follow-up of digestive system neoplasm may be early manifestations of liver metastasis. The careful follow-up of hepatic hyperperfusion disorders is necessary.

EFFECTS OF INFLAMMATORY CELLS IN COLD AND WARM ISCHEMIA-REPERFUSION INJURY OF THE GRAFTED LIVER

Objective To investigate whether the impairment of grafted livers after transplantation was induced by the same inflammatory cells both in cold and warm ischemia. Methods Male SD rats were divided into two groups at random,24 donor livers in each group were stored in Ringers solution at 4℃ for 120min or 240min of transplantation for blood sample and tissue specimen collection. Results Along with the prolongation of cold and warm ischemia time,the serum ALT,AST and LDH level increased gradually after transplantation.Under light microscopy,some hepatocytes presented necrosis after 3h and 6h of transplantation in cold ischemia,and neutrophilic infiltration in sinusoids were evident.Also,a large number of hepatocytes were necrotic 3h or 6h after transplantation in warm ischemia from NHBDs,and lymphocytic infiltration was evident in the sinusoids.The findings in electron microscopy was as the same as those of light microscopy,and the cells which infiltrated the sinusoids in warm ischemia were identified as T lymphocytes. Conclusion The impairment of grafted livers after transplantation appeared to be induced by two different kinds of inflammatory cells in cold and warm ischemia,that is,neutrophils mediated the cold ischemia-reperfusion,and T lymphocytes mediated the warm ischemia-reperfusion from NHBDs,but these findings are to be comfirmed in further investigations.