Biomedical subjects

Yuji Soejima

Publications and source records attributed to Yuji Soejima.

At least 19 recordsLinked to original sources

PubMed2006

Hyperbaric oxygen induces vascular endothelial growth factor and reduces liver injury in regenerating rat liver after partial hepatectomy.

BACKGROUND/AIMS: The aim of this study was to investigate the effect and the mechanism of hyperbaric oxygen treatment on regenerating rat liver after partial hepatectomy (PH). METHODS: Wistar rats underwent a 70% PH, followed by treatment with hyperbaric oxygen starting 8 h after PH. The regenerated liver weight and serum parameters were compared. Proliferation of both hepatocytes and sinusoidal endothelial cell (SEC) was also monitored by evaluating the proliferating cell nuclear antigen (PCNA) labeling index. Furthermore, the hepatic adenosine triphosphate levels and vascular endothelial growth factor (VEGF) protein expression were analyzed at different times. RESULTS: Hyperbaric oxygen treatment significantly reduced the serum alanine aminotransferase levels at 24 h, total bilirubin and total bile acid levels at 48 and 72 h, respectively. No significant differences in the hepatic adenosine triphosphate levels, the restitution of liver weight, or PCNA positive hepatocytes were observed between the two groups. The PCNA positive SEC, in contrast, was significantly increased in the hyperbaric oxygen group at 48h, furthermore, the hyperbaric oxygen treatment significantly increased the expression of VEGF protein in the regenerating liver at 24 and 48 h. CONCLUSIONS: Hyperbaric oxygen treatment can be considered as a therapeutic modality after massive PH.

Adenosine Triphosphate↗

PubMed2006

Successful adult-to-adult living donor liver transplantation in a patient with moderate to severe portopulmonary hypertension.

Portopulmonary hypertension (PPHTN) is one of the most devastating consequences of end-stage liver cirrhosis. When a patient has moderate to severe PPHTN, his or her candidature for liver transplantation is denied. Here we report a successful adult-to-adult living donor liver transplantation (LDLT) in a patient with moderate to severe PPHTN. The patient was a 58-yr-old female who was diagnosed with end-stage liver cirrhosis due to chronic hepatitis C. Preoperative evaluation revealed that the patient had moderate to severe PPHTN. Her mean pulmonary artery pressure (mPAP) was 35-47 mmHg without treatment. Continuous epoprostenol therapy was introduced to lower the mPAP. She underwent LDLT using an extended right hepatic lobe graft which was donated by her daughter. Prolonged artificial ventilation was necessary until postoperative day (POD) 25, after which her general condition gradually improved. By POD 72, she was in good condition and was allowed to leave the hospital. Currently, 1 yr after the operation, she visits the outpatient clinic regularly and enjoys a normal life. It should be noted, however, that the PPHTN markedly improved but did not completely resolve, as assessed by right heart catheterization 1 yr after successful LDLT.

Antihypertensive Agents↗

PubMed2006

Auxiliary partial orthotopic living donor liver transplantation for a child with congenital absence of the portal vein.

Congenital absence of the portal vein (CAPV) is a rare malformation of the mesenteric vasculature in which visceral venous blood bypasses the liver, completely draining into the systemic circulation through a congenital porto-systemic shunt. Liver transplantation has rarely been indicated for patients with this disease. We present a child with CAPV who was managed successfully by living donor auxiliary partial orthotopic liver transplantation (APOLT), while preserving the right lobe of the native liver. In conclusion, APOLT for patients with CAPV is a feasible and ideal procedure because portal vein (PV) diversion is not necessary.

Child, Preschool↗

PubMed2006

Biliary strictures in living donor liver transplantation: incidence, management, and technical evolution.

Biliary complications, biliary strictures (BS) in particular, continue to be a significant cause of morbidity after LDLT despite technical refinement. In this study, we assessed the incidence of BS and their management in living donor liver transplantation (LDLT) with special reference to the type of biliary reconstruction. A total of 182 LDLTs performed at our institution for either adult (n = 157) or pediatric (n = 25) patients were included in the study. The duct-to-duct (DD) biliary reconstruction was performed for 106 cases, while the conventional Roux-en-Y hepaticojejunostomy (HJ) was utilized for the remaining 76 cases. Overall, BS developed in 46/182 (25.3%) of the cases (DD, 26.4%; HJ, 25.0%). The 1- and 3-year cumulative incidences of BS were 22.9% and 31.9%, respectively, in the DD group, and 15.2% and 29.1%, respectively, in the HJ group (P= not significant). The left-lobe LDLT was more prone to develop BS. Continuous anastomosis tended to be associated with the high incidence of BS in the DD group. The incidence of anastomotic leak was significantly lower in the DD group. Intervention via either pre-cutaneous or endoscopic approach was successful in the majority of cases, although recurrence could occur in some patients. In conclusion, BS was not associated with the type of reconstruction in LDLT. The primary radiological or endoscopic interventions were satisfactory treatments of choice. Technical refinement is an important factor to reduce the incidence of BS.

Adult↗

PubMed2006

Reconstruction of the middle hepatic vein tributaries using the recipient's recanalized umbilical vein in right-lobe living-donor liver transplantation.

BACKGROUND: Right-lobe grafts without the middle hepatic vein (MHV) can cause severe congestion of the anterior segment in living-donor liver transplantation (LDLT). However, the indications and methods for reconstructing the MHV or its tributaries remain controversial. METHODS: We herein describe two cases of the successful use of the recipient's recanalized umbilical vein as an interposition graft to drain the major MHV tributaries in right-lobe LDLTs. RESULTS: After surgery, both right-lobe grafts are currently functioning well and all of the reconstructed venous tributaries have been confirmed to be patent by doppler ultrasonography. The histopathological features of the recanalized umbilical vein showed an intact intima with thickened media. CONCLUSIONS: The use of the recipient's recanalized umbilical vein is a good option for reconstructing MHV tributaries in right-lobe LDLTs.

Hepatic Veins↗

PubMed2006

Clinical roles of increased populations of Foxp3+CD4+ T cells in peripheral blood from advanced pancreatic cancer patients.

OBJECTIVES: Further metastasis should be avoided in pancreatic cancer (PC) patients for effective surgical treatment. Regulatory T cells (Foxp3CD4 T cells including CD4CD25 T cells and CD4CD25 T cells) play important roles in tumor immunity. This study aimed to investigate whether regulatory T cells participate in metastasis. METHODS: Peripheral blood was withdrawn from PC patients, as well as healthy volunteer donors as controls. The peripheral blood mononuclear cells (PBMCs) were subjected to FACScan analysis after labeling with anti-CD4, anti-CD25, and anti-Foxp3 antibodies. Tumor markers, including DUPAN2 and CA19-9, surface markers, such as the CD4/CD8 ratio, and the CD57 cell population were assessed. Clinical stages were classified according to the TNM classification. RESULTS: The Foxp3CD4 T-cell population among the PBMCs was significantly increased in PC patients (8.10% +/- 4.65%) compared with healthy donors (2.47 +/- 0.78%) (P < 0.001). No significant relationships existed for the tumor markers, CD4/CD8 ratio, and CD57 cells. However, a significant correlation was found between Foxp3CD4 T cells among the PBMCs and the TNM stage (P < 0.05). CONCLUSIONS: Foxp3CD4 T cells are good markers for metastasis detection in PC patients and more accurate than other conventional tumor markers, especially at advanced stages of the disease.

Aged↗

PubMed2006

Effect of hyperbaric oxygen on cold storage of the liver in rats.

BACKGROUND: The depletion of biochemical energy stores during prolonged cold storage is one of the most critical events of cold ischemia-reperfusion (CI/R) injury. The aim of this study was to evaluate the effect of hyperbaric oxygen (HBO) treatment on CI/R injury. METHODS: Livers were harvested from male Wistar rats and stored for 24 h at 4 degrees C in University of Wisconsin solution (Group 1). Others were additionally treated with HBO during the preservation period (Group 2). At the end of the 24 h cold preservation, the concentrations of hepatic enzymes and lipid peroxidation (LPO) in the effluent and the hepatic adenosine triphosphate (ATP) levels were measured. After preservation, the livers were reperfused for 90 min with an oxygenated Krebs-Henseleit bicarbonate buffer. Perfusate samples were obtained serially, and portal flow rates were also recorded. RESULTS: In group 2, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and LPO into the effluent at the end of preservation were decreased and the depletion of ATP was prevented (P<0.05). After reperfusion, the portal flow was significantly improved in group 2 (P<0.05). The time-dependent increase of alanine aminotransferase levels (ALT) observed in group 1 was suppressed significantly in group 2, and total bile production during 90 min of reperfusion was significantly greater in group 2 (P<0.05). The structure of the livers in group 2 was significantly well maintained, and the liver weight change ratio was significantly greater in group 1 (P<0.05). CONCLUSIONS: HBO treatment during cold storage seems to prevent hepatic ischemic injury and have protective effects against CI/R injury by attenuating the depletion of energy stores.

Adenosine Triphosphate↗

PubMed2005

In situ dye injection bile leakage test of the graft in living donor liver transplantation.

BACKGROUND: Bile leakage after living donor liver transplantation (LDLT) remains a serious problem, resulting in lower survival rates. The aim of this study is to clarify the benefits of in situ leakage testing of the cut surface of grafts in LDLT. METHODS: A total of 135 LDLTs were analyzed. The patients were divided into the following two groups according to the in situ dye injection leakage test of the cut surface: test group (n=40) and control group (n=40). The incidence of bile leakage and the risk factors were identified by analyzing the recipients, donors, and transplantation variables. RESULTS: Bile leakage occurred in 12.5% (10/80) of LDLTs. In the control group, there were nine cases of bile leakage (22.5%). On the other hand, there was only one case (2.5%) of bile leakage in the test group (P<0.05). The bile leakage case in the test group was resolved preservationally. However, 2 of the 9 (22.2%) bile leakage cases in the control group required surgery. CONCLUSION: Although there is biliary complication, especially bile leakage from the cut surface, as an inevitable consequence of LDLT, this study suggests that there is advantage in conducting bile leakage testing to minimize the incidence of bile leakage from the cut surface, which is associated with a high risk of graft failure.

Adult↗

PubMed2005

Impact of graft hepatic vein inferior vena cava reconstruction with graft venoplasty and inferior vena cava cavoplasty in living donor adult liver transplantation using a left lobe graft.

BACKGROUND: Hepatic venous reconstruction is critical in living donor adult liver transplantation (LDALT) because outflow obstruction in small for size graft may lead to graft dysfunction or loss. We describe the usefulness of venoplasties of the graft hepatic vein (HV) and graft HV-recipient inferior vena cava (IVC) reconstruction in LDALT using a left lobe graft. METHODS: Sixty patients who underwent LDALT were studied. We divided the patients into following two groups: venoplasty group (n=30) and control group (n=30). For the patients with venoplasty group, venoplasty of the graft and recipient IVC cavoplasty was made to widen the orifice. Comparison examination of a background factors and postoperative bilirubin and the ascites was carried out. RESULTS: The mean graft volume standard liver volume ratio (GV/SLV) did not have the difference at 41.7% of venoplasty group, and 42.1% of control group (p=NS). The diameter of the hepatic vein in control and venoplasty group before and after venoplasty is 26.9+/-5.5, 28.2+/-2.9, and 34.1+/-3.9 mm, respectively. The diameter of the hepatic vein after venoplasty is larger than that of before venoplasty and of control (P<0.05). Mean total bilirubin level on postoperative day (POD) 7 is 13.8+/-9.3 mg/dl in control group and 7.0+/-3.3 mg/dl in venoplasty group (P<0.05). Mean amount of ascites on POD 7 and 14 are 1576+/-1113 and 1397+/-1661 cc in control group, and 736+/-416 and 550+/-385 cc in venoplasty group, respectively (P<0.05). Two-year survival rate is 75.2 % in control group and 86.6 % in venoplasty group (P<0.05). CONCLUSIONS: We conclude that in LDALT using left lobe graft, HV-IVC reconstruction with graft venoplasty and IVC cavoplasty is useful not only to prevent outflow block but also to improve graft function.

Aged↗

PubMed2005

Short-term intensive treatment for donors with hepatic steatosis in living-donor liver transplantation.

BACKGROUND: The use of steatotic livers is associated with increased primary nonfunction in liver transplantation. To reduce the risk of liver injury, we applied a short-term combination therapy of diet, exercise and drugs for 11 living-donor liver transplantation (LDLT) candidates with steatosis. METHODS: Subjects were treated with a protein-rich (1000 kcal/day) diet, exercise (600 kcal/day), and bezafibrate (400 mg/day) for 2-8 weeks. RESULTS: The treatment significantly improved macrovesicular steatosis (30+/-4% vs. 12+/-2% [mean +/- SEM], P = 0.0028). Body weight and BMI were significantly reduced (73.7 +/- 3.2 kg vs. 66.9 +/- 2.9 kg, P = 0.0033, 26.4 +/- 0.7 kg/m vs. 24.1 +/- 0.8 kg/m, P = 0.0033). The treatment completely normalized liver function tests and lipid metabolism. Seven treated liver grafts (left lobe) were transplanted to the recipients. We compared transplanted graft function and resected liver function of donors using parameters such as peak total bilirubin, prothrombin time at postoperative day 3, and peak alanine aminotransferase between treated liver (n = 7) and donor liver without hepatic steotosis (n = 37). The transplanted grafts showed good liver functions, and there was no difference between them with respect to functional parameters. The treated donors also showed good liver functions, and no significant differences in functional parameters. CONCLUSIONS: The results of this study indicate that our short-term treatment effectively reduced steatosis and contributed to safer LDLT. Our findings also suggest that even severely steatotic livers can be used for LDLT grafting subsequent to our short-term treatment regimen.

Adult↗

PubMed2005

Validity of preoperative volumetric analysis of congestion volume in living donor liver transplantation using three-dimensional computed tomography.

Reconstruction of middle hepatic vein (MHV) tributaries is controversial in right-lobe living donor liver transplantation (LDLT). This study aimed to evaluate the appropriateness of reconstructing MHV tributaries by volumetry using 3-dimensional computed tomography (3D-CT). Between November 2003 and January 2005, 42 donor livers (right-lobe graft, n = 25; left-lobe graft, n = 17) were evaluated using this software. The total congestion volume (CV) associated with the MHV tributaries and the inferior right hepatic vein (IRHV), and graft volume (GV) were calculated. In recipients with right-lobe grafts, CV/(right liver volume [RLV]) and (GV - CV)/(standard liver volume [SLV]) were compared between 2 groups: with reconstruction (n = 16) and without reconstruction (n = 9). To evaluate the influence of CV on the remnant right lobe in donors, total bilirubin was compared between 2 groups: high CV (CV > 20%, n = 13) or low CV (CV < or = 20%, n = 4). The mean CV/RLV ratio was 32.3 +/- 17.1% (V5, 15.2 +/- 9.9%; V8, 9.2 +/- 4.1%; and IRHV, 8.5 +/- 11.4%) and the maximum ratio was as high as 80.8%. The mean (GV - CV)/SLV ratio before reconstruction in patients with or without reconstruction resulted in 33.5 +/- 12.8% and 55.4 +/- 12.9%, respectively (P < 0.01). In donors, total bilirubin was significantly high in the high CV group on postoperative day 1 compared with the low CV group (P < 0.05). In conclusion, calculation of CV using 3D-CT software proved to be very useful. We concluded that this evaluation should be an integral part of procedure planning, especially for right-lobe LDLT.

Adult↗

PubMed2005

Effect of liver transplantation on multiple bone fractures in an infant with end-stage biliary atresia: a case report.

Osteodystrophy is frequently found in children with chronic cholestatic liver disease. We herein report an end-stage case of biliary atresia that was associated with multiple bone fractures and severe growth retardation. The patient, an 8-month-old female, underwent a living-related liver transplantation and thereafter showed a dramatic improvement in growth and decrease in bone fractures. A correction of the liver function is therefore considered to be a key factor in treating osteodystrophy that is related to chronic cholestatic liver disease. It is also essential to perform liver transplantation at the most appropriate time to enhance and support the growth of these patients.

Biliary Atresia↗

PubMed2005

Fatty liver caused by portal vein thrombosis after living donor liver transplantation: a case report.

Portal vein thrombosis (PVT) is a rare complication that occurs after liver transplantation: however, it cannot be ignored as a cause of graft loss and death. We herein report a pediatric case of PVT that caused a fatty change in the graft after living donor liver transplantation. The portal vein was successfully reconstructed using the left great saphenous vein of the same donor. Moreover, the fatty liver recovered after the operation. Our case suggests that the finding of fatty liver is an important marker of PVT and immediate portal reconstruction is performed.

Fatty Liver↗

PubMed2005

Effect of intraportal infusion to improve small for size graft injury in living donor adult liver transplantation.

The most important problem in the living donor adult liver transplantation (LDALT) is a small for size graft. Although a right lobe graft is used in many cases in order to avoid small for size graft, for a donor, the risk has few in left lobe graft. We evaluate the effect of an intraportal infusion treatment to the small for size graft. One hundred and twelve patients who underwent LDALT were studied. The graft weight recipient standard liver volume ratio (GV/SLV) of these patients were 50% or less. We divided the patients into following two groups; infusion group (n = 53) and control group (n = 59). For the infusion group, 16 G double lumen catheter was inserted into portal vein and nafamostat mesilate (protease inhibitor which stabilize coagulofibrinolytic state; 200 mg/day), prostaglandin E(1) (vasodilator and hepatoprotective effect; 500 microg/day) and thromboxane A(2) synthetase inhibitor (vasodilator and anticoagulant effect; 160 mg/day) were administrated continuously for 7 days. Small-for-size graft syndrome was defined as bilirubin >10 mg/dl and ascites >1000 cc on postoperative day (POD) 14. Comparison examination of a background factors and postoperative bilirubin and amount of ascites was carried out. The mean GV/SLV did not have the difference at 39.1% of infusion group, and 38.3% of control group (P = 0.58). By the control group, 15 patients (25.4%) were small-for-size graft syndrome, however, there was only two (3.8%) small-for-size graft syndrome in infusion group (P = 0.04). The bilirubin levels of infusion and control group on 7 and 14 POD were 9.9 and 7.8 vs. 9.5 and 10.5 mg/dl, respectively. The amount of ascites of infusion group on 7 and 14 POD were 870 and 430 cc, respectively. On the contrary, in control group, the amount of ascites on 7 and 14 POD were 1290 and 1070 cc, respectively. Bilirubin levels and the amount of ascites on 7 and 14 POD were lower in the patients with infusion group then those with control group. There were no differences between infusion group and control group in age, sex and Child's classification. The intraportal infusion had an effect in prevention of hyperbilirubinemia and loss in quality of excessive ascites in the patients with small for size graft. This was suggested to be what is depended on the improvement of the microcirculation insufficiency considered one of the causes of small-for-size graft syndrome.

Adult↗

PubMed2005

Influence of HLA compatibility and lymphocyte cross-matching on acute cellular rejection following living donor adult liver transplantation.

BACKGROUND: Reports on the relevance of immunogenetic factors in living donor adult liver transplantation (LDALT) are often conflicting or inconclusive. We therefore investigated the human leukocyte antigen (HLA) mismatches, lymphocyte crossmatch positivity, and the reactivity in mixed lymphocyte culture (MLC) in a series of LDALT. METHODS: A total of 104 LDALT patients were studied. The minimum follow-up was 12 months, and the graft survival rates were assessed. The incidence of the most common complications was analyzed. And the influence of HLA, the flow cytometric analysis findings, enhanced cytotoxic cross-matching and MLC on graft survival, and acute rejection was also investigated. RESULTS: As a result, 96 negative cross-matching and eight positive cross-matching cases were identified. Positive cytotoxic cross-matching had a significant effect on graft survival (P<0.05), while flow cytometric cross-matching also had an additional effect on acute rejection (P<0.05). The MLC of the patients with three HLA mismatches was significantly higher than the MLC of patients with zero HLA mismatches. The incidence of acute cellular rejection (ACR) was higher in the patients with three mismatches than in the other patients, and moderate rejection only occurred in the patients with three mismatches. CONCLUSION: HLA mismatching was not statistically associated with the overall graft survival after LDALT. The graft failure rates were higher in the positive cross-matching cases and therefore a strong immuosuppressant might be needed for positive cross-matching cases.

Acute Disease↗

PubMed2005

Prevention of hepatitis B virus infection from hepatitis B core antibody-positive donor graft using hepatitis B immune globulin and lamivudine in living donor liver transplantation.

BACKGROUND: Hepatic grafts from hepatitis B surface antigen-negative and anti-core antibody (HBcAb)-positive donors have been shown to transmit hepatitis B virus (HBV) infection. Recently, it has been reported that combined hepatitis B immune globulin (HBIG) and lamivudine therapy is effective in the prevention of hepatitis B recurrence after living donor liver transplantation (LDLT). In this report, we assessed the efficacy of combined HBIG and lamivudine therapy in preventing HBV transmission by graft with HBcAb-positive donors. METHODS: We studied 22 patients who had undergone LDLT with allografts from HBcAb-positive living donors at Gunma University Hospital and Kyushu University Hospital. Long-term combined HBIG and lamivudine therapy were administrated to all recipients. Serum samples from the donor and recipient were tested for HBcAb, HBV DNA, and hepatitis B surface antibody. Liver biopsies from grafts were tested for HBV DNA. RESULTS: All recipients were HBcAb negative before LDLT. All of the donor livers were HBV DNA positive at the time of LDLT. All of the recipients had HBsAb titers greater than 300 mIU/ml 4 weeks after LDLT, and remained 100 mIU/ml thereafter. None of the recipients have become infected with HBV with a follow-up of 25-86 months. CONCLUSIONS: Perioperative combined HBIG and lamivudine therapy can prevent HBV infection in recipients who receive liver grafts from HBcAb-positive donors.

Adolescent↗

PubMed2004

IL-12 gene therapy is an effective therapeutic strategy for hepatocellular carcinoma in immunosuppressed mice.

Immunosuppressive therapy for organ transplantation is essential for controlling rejection. When liver transplantation is performed as a therapy for hepatocellular carcinoma (HCC), recurrent HCC is one of the most fatal complications. In this study, we show that intratumoral murine IL-12 (mIL-12) gene therapy has the potential to be an effective treatment for malignancies under immunosuppression. C3H mice (H-2(k)), injected with FK506 (3 mg/kg) i.p., were s.c. implanted with 2.5 x 10(6) MH134 cells (H-2(k)) and we treated the established HCC with electroporation-mediated gene therapy using mIL-12 plasmid DNA. Intratumoral gene transfer of mIL-12 elevated intratumoral mIL-12, IFN-gamma, and IFN-gamma-inducible protein-10, significantly reduced the number of microvessels and inhibited the growth of HCC, compared with HCC-transferred control pCAGGS plasmid. The inhibition of tumor growth in immunosuppressed mice was comparable with that of mIL-12 gene therapy in immunocompetent mice. Intratumoral mIL-12 gene therapy enhanced lymphocytic infiltration into the tumor and elicited the MH134-specific CTL response even under FK506. The dose of FK506 was sufficient to prevent the rejection of distant allogenic skin grafts (BALB/c mice, H-2(d)) and tumors, B7-p815 (H-2(d)) used as transplants, during mIL-12 gene therapy against MH134. Ab-mediated depletion studies suggested that the inhibition of tumor growth, neovascularization, and spontaneous lung metastasis by mIL-12 was dependent almost entirely on NK cells and partially on T cells. These results suggest that intratumoral mIL-12 gene therapy is a potent effective strategy not only to treat recurrences of HCC in liver transplantation, but also to treat solid malignant tumors in immunosuppressed patients with transplanted organ.

Angiogenesis Inhibitors↗

PubMed2004

Involvement of Rho-kinase in cold ischemia-reperfusion injury after liver transplantation in rats.

BACKGROUND: Reperfusion of ischemic tissues is known to cause the generation of reactive oxygen species (ROS) with resultant tissue damage. However, the sources of ROS in reperfused tissues are not fully characterized. We hypothesized that the small GTPase Rho and its target effector Rho-kinase/ROK/ROCK are involved in the oxidative burst in reperfused tissue with resultant reperfusion injury. METHODS: In an in vivo rat model of liver transplantation using cold ischemia for 12 hr followed by reperfusion, a specific Rho-kinase inhibitor, fasudil (30 mg/kg), was administered orally 1 hr before the transplantation. RESULTS: Fasudil suppressed the ischemia-reperfusion (I/R)-induced generation of ROS after reperfusion (P<0.01) and also suppressed the release of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta) 3 hr after reperfusion, resulting in a significant reduction of I/R-induced hepatocellular injury (P<0.05), necrosis, apoptosis (P<0.01), and neutrophil infiltration (P<0.0001) 12 hr after reperfusion. All animals receiving a graft without fasudil died within 3 days, whereas 40% of those receiving fasudil survived (P<0.001). CONCLUSIONS: The present study demonstrates that Rho-kinase-mediated production of ROS and inflammatory cytokines are substantially involved in the pathogenesis of hepatocellular necrosis and apoptosis induced by cold I/R in vivo and that Rho-kinase may be regarded as a novel therapeutic target for the disorder.

Alanine Transaminase↗