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PubMed1992

Vasoactive intestinal peptide receptors in rat liver after partial hepatectomy.

We describe the status of vasoactive intestinal peptide (VIP) receptors in regenerating liver. VIP-stimulated adenylate cyclase activity was markedly decreased in proliferating liver 3 days after partial (70%) hepatectomy. This was associated with a reduced efficacy of VIP (53% compared with controls), with no change in the potency of the peptide (ED50 0.8 nM). In contrast, forskolin- and guanosine 5'-[beta gamma-imido]triphosphate (Gpp[NH]p)-stimulated enzyme activities were not decreased after hepatectomy. The expression of Gs protein subunits (alpha and beta) was studied by cholera toxin-catalysed ADP ribosylation of alpha s and by immunoblotting of alpha s and beta subunits. Both subunits were increased in regenerating liver, further suggesting that the decreased response to VIP was not related to a decreased expression of Gs proteins. In fact, the reduced adenylate cyclase response to VIP in regenerating liver was associated with quantitative and structural changes in VIP receptors. Equilibrium binding data obtained with 125I-VIP indicated the presence of two classes of binding sites, the Kds of which were not altered after hepatectomy. In contrast, changes in binding capacity (Bmax.) were as follows: 0.11 +/- 0.01 and 0.05 +/- 0.01 pmol/mg of protein for high-affinity sites in control and hepatectomized rats respectively; and 2.3 +/- 0.2 and 0.65 +/- 0.03 pmol/mg of protein for low-affinity sites in control and hepatectomized rats respectively. Moreover, affinity labelling experiments showed that the M(r) value of 125I-VIP-receptor complexes was higher in regenerating liver than in quiescent hepatocytes, e.g. 58,000 and 53,000 respectively. It is concluded that VIP receptors are altered in regenerating liver, resulting in a decreased response of adenylate cyclase to the neuropeptide.

Adenosine Diphosphate Ribose↗

PubMed1982

Total hepatectomy and hepatic vascular exclusion in the rat: a comparison, with special reference to the influence of body temperature.

1. The effects of two procedures for dehepatization, total hepatectomy and complete hepatic vascular exclusion were compared in the rat, and the influence of decreasing the body temperature from 37.5 degrees to 35.5 degrees C on the course of dehepatization was evaluated. 2. The duration of survival after total hepatectomy was 5.75 +/- SD 0.67 h at 37.5 degrees C and 8.51 +/- 0.78 h at 35.5 degrees C (P less than 0.001). The duration of survival after complete hepatic vascular exclusion was 5.61 +/- 1.06 h at 37.5 degrees C and 8.30 +/- 0.70 h at 35.5 degrees C (P less than 0.001). 3. It is concluded that (a) the duration of survival does not differ after total hepatectomy and after complete vascular exclusion, which suggests that substances released by the necrotic liver have no influence on the course of dehepatization, and (b) the body temperature has an influence on the course of dehepatization and must be carefully monitored in the comparison of the different procedures for hepatization and in the assessment of experimental therapeutic methods for acute liver failure.

Alanine Transaminase↗

PubMed2002

Liver fibrosis increases the risk of intrahepatic recurrence after hepatectomy for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) commonly develops in patients with chronic hepatitis. Intrahepatic recurrence after hepatectomy often includes nodules of new tumour in the liver remnant. The aim of this study was to examine hepatitis-related factors that might predict this type of recurrence. METHODS: The influence of various hepatitis-related factors on intrahepatic recurrence of HCC was studied by multivariate analysis in 138 patients who underwent curative resection and were followed for more than 2 years. RESULTS: The Cox proportional hazard model showed that histological evidence of fibrosis of the underlying liver was the most significant predictive factor for intrahepatic recurrence (P = 0.001). Serum albumin level was also significantly associated with recurrence (P = 0.038). The relative risks of histological fibrosis and low serum albumin levels were 8.9 and 1.7 respectively. Among tumour-related factors, only tumour size was significantly associated with recurrence (P = 0.017). Major hepatectomy was also an independent risk factor for intrahepatic recurrence (P = 0.004). CONCLUSION: Histological evidence of fibrosis and low serum albumin levels are useful predictors of intrahepatic recurrence after hepatectomy, presumably owing to metachronous multifocal tumour in the liver remnant.

Adolescent↗

PubMed1999

Experimental study of the effect of intraportal prostaglandin E1 on hepatic blood flow during reperfusion after ischaemia and hepatectomy.

BACKGROUND: Prostaglandin E1 (PGE1) has protective effects experimentally and clinically in individual models of hepatic ischaemia-reperfusion injury and of partial hepatectomy. The present study investigated the effects of intraportal administration of PGE1 on hepatic blood flow, systemic arterial pressure and long-term animal survival after 60 min of total liver ischaemia followed by 70 per cent partial hepatectomy in rats. METHODS: Total liver ischaemia was induced by occluding the hepatoduodenal ligament for 60 min. PGE1 0.5 microg per kg per min was infused intraportally for 15 min before inducing ischaemia and for 120 min after ischaemia in the treatment group. Normal saline was infused in the control group. During ischaemia 70 per cent partial hepatectomy was performed. Portal venous flow (PVF), peripheral tissue blood flow (PTBF) and hepatic artery flow were measured before and after ischaemia. Serum biochemical analysis was carried out at 1, 3 and 24 h, and 7 and 14 days; and liver histology at 1 and 24 h, and 7 days after reperfusion. Survival was followed for 1 year. RESULTS: Intraportal infusion of PGE1 significantly improved PVF and PTBF without affecting the systemic arterial pressure. Long-term survival was significantly higher in the PGE1 group. Serum aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase levels decreased significantly, and 2-h bile flow was significantly improved, in the PGE1 group. Histological examination revealed significant portal venous congestion, sinusoidal congestion, fatty degeneration and tissue necrosis 24 h and 7 days after reperfusion in the control group. CONCLUSION: PGE1 has a protective effect against liver damage when the liver is injured by warm ischaemia and reperfusion followed by partial resection.

Alprostadil↗

PubMed2001

Postoperative liver function after elective right hepatectomy in elderly patients.

BACKGROUND: Because the influence of age on the risk of liver resection is controversial, the outcome of major liver resection in patients older than 65 years was evaluated. METHODS: Between 1990 and 1997, 24 patients aged 65 years or more underwent elective right hepatectomy (segments V-VIII) for a malignant liver tumour arising in a normal liver. They were evaluated retrospectively in terms of operative deaths, morbidity and postoperative liver function, and compared with 22 patients aged 40 years or less who had undergone a similar resection during the same interval. RESULTS: Elective right hepatectomy in patients aged 65 years or more resulted in a similar number of deaths (one versus none) and a similar severe complication rate (12 versus 5 per cent) to that observed in patients aged 40 years or less. Evaluation of liver function on days 2, 5 and 8 after operation, in patients aged 65 years or more and 40 years or less, showed that mean prothrombin time was 52 versus 56 per cent, 58 versus 62 per cent and 76 versus 72 per cent respectively (P not significant) and that the mean total serum bilirubin level was 35 versus 38 micromol/l, 32 versus 36 micromol/l and 25 versus 28 micromol/l (P not significant). Postoperative levels of aminotransferases, gamma-glutamyl transpeptidase and alkaline phosphatase were similar in the two groups. Mean(s.d.) duration of hospital stay was 15(7) days in patients aged 65 years or more and 13(4) days in the younger patients. CONCLUSION: Postoperative liver function after elective right hepatectomy in selected patients older than 65 years was similar to that in younger patients.

Adolescent↗

PubMed2002

Sequential resection of lung metastasis following partial hepatectomy for colorectal cancer.

BACKGROUND: Multiple organ metastases from colorectal carcinoma may be considered incurable, but long survival after both liver and lung resection for metastases has been reported. METHODS: A retrospective analysis of 48 patients who underwent lung resection for metastatic colorectal cancer between 1992 and 1999 was undertaken. Twenty-seven patients had lung metastasis alone, 15 had previous partial hepatectomy, and six had previous resection of local or lymph node recurrence. The relationship of clinical variables to survival was assessed. Survival was calculated from the time of first pulmonary resection. RESULTS: Five-year survival rates after resection of lung metastasis were 73 per cent in patients without preceding recurrence, 50 per cent following previous partial hepatectomy and zero after resection of previous local recurrence. Independent prognostic variables that significantly affected survival after thoracotomy were primary tumour histology and type of preceding recurrence. There was no significant difference in survival after lung resection between patients who had sequential liver and lung resection versus those who had lung resection alone. CONCLUSION: Sequential lung resection after partial hepatectomy for metastatic colorectal cancer may lead to long-term survival.

Adult↗

PubMedDate not supplied

Changes in serum levels of apolipoprotein A-1 as an indicator of protein metabolism after hepatectomy.

The clinical significance of serum apolipoprotein A-1 levels as an indicator of hepatic protein synthesis after hepatectomy was investigated. A total of 50 patients who had undergone hepatectomy at our department from 1997 to 1999 were selected for this study. The serum levels of apolipoprotein A-1, indocyanine green dye retention at 15 minutes, lectin-cholesterol acyltransferase, prealbumin, and high-density lipoprotein cholesterol were measured in these patients preoperatively and on postoperative days 7 and 14. The type of hepatic resection conducted was partial resection in 13 cases, subsegmentectomy in 13 cases, segmentectomy in five cases, and bisegmentectomy in 19 cases. All the patients tolerated the operation, and none of the cases had any severe complications, such as liver failure. In most cases, the serum apolipoprotein A-1 levels decreased on postoperative day 7 and recovered by day 14. There were no significant differences in the changes in apolipoprotein A-1 levels between patients with the individual types of operative procedures. The serum apolipoprotein A-1 levels showed significant correlations with the serum high-density lipoprotein cholesterol, lectin-cholesterol acyltransferase and prealbumin levels on postoperative days 7 and 14; however, there was no significant correlation with the indocyanine green retention test. When the cases were divided into three groups according to the serum level of apolipoprotein A-1 on postoperative day 7 (group A: over 81 mg/dl, group B: 61-80 mg/dl, group C: under 60 mg/dl), the serum indocyanine green retention, prealbumin, lectin-cholesterol acyltransferase and high-density lipoprotein cholesterol levels in group C were significantly lower than those in group A on postoperative day 7. On the basis of these results, it is suggested that the pattern of changes in the serum apolipoprotein A-1 levels may be a good indicator of the hepatic protein synthetic ability during the perioperative period after hepatectomy.

Aged↗

PubMed2001

Global changes in interleukin-6-dependent gene expression patterns in mouse livers after partial hepatectomy.

Liver regeneration following 70% partial hepatectomy leads to rapid activation of genes in the remnant liver. Interleukin-6 deficient (IL-6 -/-) mice have impaired liver regeneration and abnormalities in immediate early gene expression. In this study, the gene expression program in the IL-6 +/+ and -/- livers at 2 hours posthepatectomy was examined with a cDNA array representing 588 highly regulated mouse genes. Thirty-six percent of the 103 immediate early genes were induced differently in IL-6 +/+ compared with IL-6 -/- livers, implying regulation by IL-6. IL-6 treatment of the IL-6 -/- mice in the absence of hepatectomy induced a much smaller set of genes in the liver, suggesting that IL-6 cooperates with other hepatectomy-induced factors to activate the large number of genes. Northern blot analyses were used to verify gene expression data obtained from the arrays. The expression of urokinase type plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1), critical components of the urokinase plasminogen activator (uPA) system, was lower and delayed in IL-6 -/- livers. Despite the fact that active uPAR/uPA complex is critical for hepatocyte growth factor (HGF) activation, no differences were detected between the IL-6 +/+ and -/- livers in HGF activation as measured by receptor phosphorylation. On the contrary, the mitogen-activated protein kinase (MAPK) pathway was activated in IL-6 +/+ livers early during regeneration but remarkably delayed in IL-6 -/- livers. Defective liver regeneration may be explained by the large number of gene activation pathways altered in IL-6 -/- livers and further supports the finding that IL-6 is necessary for normal liver regeneration.

Animals↗

PubMed2003

Interleukin 6 is important for survival after partial hepatectomy in mice.

The response to partial hepatectomy (PH) is impaired in interleukin 6 (IL-6)-deficient mice. IL-6 is well known for its role in the induction of the acute phase (AP) response, and the impairment of this response after surgery and hepatectomy could explain the defective hepatocyte regeneration. In addition, it was proposed that IL-6 has an important role in stimulating the reentry of quiescent cells into the cell cycle within the first 2 to 4 hours after PH. To further analyze the role for IL-6, we performed two third hepatectomies in wild-type mice, in IL-6 knockout (KO) mice, and in IL-6 KO mice that were treated 30 minutes before surgery with intravenous (IV) (short acting) or subcutaneous (SC) (long acting) injections of recombinant IL-6. The high postoperative mortality of IL-6-deficient mice could be completely prevented by SC, but not by IV IL-6 treatment, showing the requirement of a sustained action of IL-6. However, there is a subset of IL-6 KO mice that survives a PH in good health even without IL-6 treatment. When we analyzed these mice, we found an intact liver regeneration and no indication of a block in cell cycle reentry. We conclude that the major role of IL-6 is the induction of an adaptive response to PH that ensures body homeostasis and survival.

Acute-Phase Proteins↗

PubMedDate not supplied

A model of partial hepatectomy in mice.

A versatile, simple, and reproducible model of hepatectomy is essential for the study of liver regeneration and its effects on various pathological processes. A murine model of liver resection and regeneration suitable for research is described. Male inbred CBA mice 6-8 wk old were used in all experiments. The contribution of the hepatic lobes to the total liver mass was determined by wet weight measurements. Resection of 37% (n = 10) and 70% (n = 10) liver volume was performed using hemostatic clips to ligate the hepatic lobe pedicles. Animals were recovered and subsequently killed 21 days postoperatively Liver mass was determined and compared to control animals (n = 17) to assess the completeness of liver regeneration. There were no operative deaths in animals undergoing either 37% or 70% hepatectomy. The procedures could be performed expediently, and animal recovery was complete. Liver mass (grams) assessed 21 days postoperatively [mean (SE)] in both the 37% resection, 1.76 g (0.07), and 70% resection, 1.56 g (0.05), groups was not significantly different from control animals, 1.64 g (0.07) (p =.265). Thus, partial hepatectomy can be performed safely and rapidly in mice using haemostatic clip ligation of hepatic lobes, with no impairment to the subsequent process of liver regeneration.

Animals↗

PubMed1977

Induction of pinocytosis in rat hepatocytes by partial hepatectomy.

Rat hepatocytes, normally not highly pinocytic cells, becomes so after partial hepatectomy when about two-thirds of the liver is removed. Droplets, up to 20 mum in diameter, develop, initially by addition to smaller pinocytic structures and later by fusion with lysosomes. The droplets contain a material with an electron microscope periodicity characteristic of fibrin; they are periodic acid Schiff-positive as is plasma. It is therefore reasonable to consider plasma glycoproteins to be major components of the droplets. The droplets are at all times membrane delimited, an observation possible only after perfusion fixation. The droplets are positive for three lysosomal hydrolases identified cytochemically: acid phosphatase, N-acetyl-beta-glucosaminidase, and beta-glucuronidase. From light and electron microscopy it is evident that these activities are acquired by fusion with lysosomes, mostly autophagic vacuoles and residual bodies both of which become very numerous after partial hepatectomy. Pinocytic structures are seen relatively infrequently in the hepatocytes of normal rats but a great many are present after partial hepatectomy. They are most easily observed if horseradish peroxidase (HRP) is intravenously injected before sacrifice and sections are incubated for HRP cytochemistry. The low dose of HRP employed (10 mg/100 g body weight) does not induce pinocytosis in controls, either untreated rats or rats subjected to laparotomy, including palpation of the liver. However, in partially hepatectomized rats even a much smaller dose of intravenous HRP (3.3 mg/100 g) visualizes the pinocytic structures in hepatocytes (coated vesicles, channels, cuplike bodies, and droplets). Kupffer cells pinocytose much HRP in both control and partially hepatectomized rats.

Acetylglucosaminidase↗

PubMed2000

Priming of hepatocytes for cell culture by partial hepatectomy prior to cell isolation.

The combination of ex vivo gene transfer and a sufficient transplant model for hepatocytes may permit treatment of single enzyme-based metabolic liver diseases. Induction of replicative potential (priming) in hepatocyte cultures may enhance the efficiency of gene transfer under stable in vitro conditions. It is known that hepatocyte replication is increased in vivo after partial hepatectomy. We investigated the effect of partial hepatectomy prior to cell isolation on hepatocytes in vitro. Male Lewis rats served as donors. Hepatocytes were isolated by collagenase digestion from either intact livers or from livers 48 h after 70% hepatectomy (PH). Cells were seeded on collagen-coated culture dishes with hormone-supplemented culture media. Hepatocyte morphology, number, albumin secretion rate, and mono-ethyl-glycin-xylidid (MEGX)-biotransformation capacity were assessed on days 1, 3, and 5 in culture. PH significantly increased hepatocyte number and albumin secretion of cultured hepatocytes over the whole observation period. In contrast, MEGX-biotransformation capacity was significantly decreased. Morphology of cultured hepatocytes was not affected by PH prior to hepatocyte isolation. These results suggest a prolonged and complex response of hepatocytes to PH in vitro. Hepatocyte priming by PH is a promising approach toward stable cultures of proliferating hepatocytes and may provide a model for in vitro studies of hepatic regeneration mechanisms. Further research on hepatocyte priming toward an application in ex vivo gene transfer and hepatic tissue engineering seems justified.

Animals↗

PubMed1979

The effect of intragastric feeding with amino acids on liver regeneration after partial hepatectomy in the rat.

The incorporation of 14C-thymidine into DNA was measured at 4-hr intervals from 16 to 32 hr after partial hepatectomy in groups of rats. Rats forcefed solutions of amino acids or branched-chain amino acids showed a significant reduction in the DNA specific activity 24 hr after partial hepatectomy when compared to rats forced fed an equal volume of water. Intragastric feeding with ketoanalogues of the branched-chain amino acids did not alter thymidine incorporation into DNA significantly. The finding that intragastric feeding depresses DNA synthesis after partial hepatectomy contrasts with our studies indicating increased synthesis of albumin in partially hepatectorized animals receiving similar feeding and indicates different control mechanisms for DNA and albumin synthesis.

Amino Acids↗

PubMed1993

Partial hepatectomy of rats 3 weeks before or simultaneously with 2-aminofluorene injection can affect the amounts of adducts induced in hepatic DNA.

The influence of partial hepatectomy on the level of 2-aminofluorene (2-AF) induced DNA adducts in rat liver was studied. We found that partial hepatectomy performed either 3 weeks before or simultaneously with the injection of 2-AF affected the amounts of adducts in rat hepatic DNA compared to controls. The level of DNA adducts in rats that were treated with 2-AF and simultaneously hepatectomized was higher (19.9 fmol/microgram DNA) than in non-hepatectomized ones (14.4 fmol/microgram DNA) when measured 48 h after 2-AF administration. In rats treated with the carcinogen 3 weeks after hepatectomy the level of DNA adducts was significantly higher than in nonhepatectomized rats when measured 15 days after the injection of 2-AF (10.9 fmol/microgram DNA and 5.9 fmol/microgram DNA respectively). The high level of DNA adducts in that group of hepatectomized animals was correlated with a relatively lower rate of 2-AF-induced radioactive thymidine incorporation into hepatic DNA (in comparison to non-hepatectomized rats).

Animals↗

PubMed1997

Time course comparison of cell-cycle protein expression following partial hepatectomy and WY14,643-induced hepatic cell proliferation in F344 rats.

During recent years, there has been an extensive research focus in the area of cell-cycle control in eukaryotes and the relationship that exists between cell proliferation and cancer. The eukaryotic cell-cycle is governed by signal transduction pathways mediated by complexes of cyclin dependent kinases (CDK) and their partner cyclin proteins. This study was performed to identify differences in cell-cycle control protein expression following physical and chemical stimuli of hepatic cell growth. Protein levels of cell cycle mediators, cyclin dependent kinases (CDK 1,2,4,5), cyclin proteins (A,B,D1-D3 and E), proliferating cell nuclear antigen (PCNA), tumor suppressor proteins (p53 and Rb), and CDK inhibitory proteins (p16Ink4, p21Waf1 and p27Kip1) were examined in F344 rats following 70% partial hepatectomy or a single dose of WY14,643 over 96- and 48-h time courses, respectively. CDK1 (p34cdc2) and PCNA protein concentrations, quantified by ELISA, were significantly increased beginning at the 24-h time point and maximal at 48 h (6.9- and 3.7-fold for partial hepatectomy and 4.2- and 3.3-fold for WY14,643, respectively). Differential effects were observed with the G1 cell-cycle mediators CDK4, CDK5, and cyclin D3, p21Waf1 and p27Kip1 CDK inhibitory protein concentrations rose in accordance with the induction of DNA synthesis and histone H1 kinase activity. In addition, there were dramatic differences in p53 protein expression patterns following partial hepatectomy versus WY14,643 dosing. Because non-genotoxic hepatocarcinogens are known to induce cellular proliferation, data generated from this study may aid in elucidating the specific hepatocarcinogenic signal transduction pathways stimulated by non-genotoxic carcinogens.

Animals↗

PubMed1991

Human liver regeneration after major hepatectomy. A study of liver volume by computed tomography.

Regeneration of the remnant liver after major hepatectomy in humans was studied by computed axial tomography (CT) in 12 noncirrhotic and five cirrhotic patients. Liver volumes were measured by abdominal CT 3 days, 10 days, 3 months, 6 months, 1 year, and 1.5 years after resection. Of the 17 patients, liver remnant volume was increased in 21.2% +/- 6.7% and 30.6% +/- 12.7% at 3 months and 6 months after resection, respectively. Noncirrhotic livers were 28.4% +/- 9.5% and 48.4% +/- 17.8% larger at 3 and 6 months. For cirrhotic livers, the increase was 8.5% +/- 3.6% and 12.9% +/- 4.5%. In five patients with right hepatectomy (65% resection), the liver remnant volumes were increased 38.4% +/- 11.7%, 48.0% +/- 16.2% and 95.1% +/- 4.5% at 3 months, 6 months, and 1 year after resection, respectively. In seven patients with right partial hepatectomy (30% to 35% resection), the percentages were 7.4% +/- 3.2%, 21.8% +/- 8.4%, and 63.9% +/- 18.3% and in five patients with left lateral segmentectomy (15% resection), they were 15.6% +/- 8.2%, 27.8% +/- 12.2%, and 33.0% +/- 14.5% 3 months, 6 months, and 1 year after resections, respectively. Noncirrhotic livers showed better regeneration than cirrhotic livers. Complete regeneration took about 1 year. The noncirrhotic liver that underwent right lobectomy also needed 1 year to double its postresection volume.

Adult↗

PubMed1999

Effect of major hepatectomy on glucose and lactate metabolism.

BACKGROUND: The liver plays an important role in glucose and lactate metabolism. Major hepatectomy may therefore be suspected to cause alterations of glucose and lactate homeostasis. METHODS: Thirteen subjects were studied: six patients after major hepatectomy and seven healthy subjects who had fasted overnight. Glucose turnover was measured with 6,6(2)H glucose. Lactate metabolism was assessed using two complementary approaches: 13C-glucose synthesis and 13CO2 production from an exogenous 13C-labeled lactate load infused over 15 minutes were measured, then the plasma lactate concentrations observed over 185 minutes after lactate load were fitted using a biexponential model to calculate lactate clearance, endogenous production, and half-lives. RESULTS: Three to five liver segments were excised. Compared to healthy controls, the following results were observed in the patients: 1) normal endogenous glucose production; 2) unchanged 13C-lactate oxidation and transformation into glucose; 3) similar basal plasma lactate concentration, lactate clearance, and lactate endogenous production; 4) decreased plasma lactate half-life 1 and increased half-life 2. CONCLUSIONS: Glucose and lactate metabolism are well maintained in patients after major hepatectomy, demonstrating a large liver functional reserve. Reduction in the size of normal liver parenchyma does not lead to hyperlactatemia. The use of a pharmacokinetic model, however, allows the detection of subtle alterations of lactate metabolism.

Adult↗

PubMed1998

Endothelin in liver cell injury and regeneration after 70% hepatectomy with portal ischemia.

Hepatic ischemia-reperfusion (IR) injury caused by portal vein clamping is a common problem in hepatobiliary surgery. Endothelin (ET) is a potent vasoconstrictor and is associated with IR injury. This study evaluated the effect of ET on liver cell injury and hepatic regeneration after hepatectomy with IR. The portal veins of rats were clamped for 20 min, then unclamped and a 70% partial hepatectomy was performed. TAK-044 (TAK), the nonselective ETA/ETB receptor antagonist, was administered s.c. 30 min before laparotomy [TAK(+)]. Portal blood ET-1, GOT levels, hepatic blood flow, histologic change, DNA synthesis of hepatocytes, and the relationship of Ito cells and perisinusoidal cells were evaluated. ET-1 concentration increased after IR and was significantly higher in the TAK(+) group owing to the blockade of ET receptors. Increased GOT levels and sinusoidal congestion were reduced, but DNA synthesis of hepatocytes and hepatic blood flow did not change in the TAK(+) group. Changes in desmin staining showed that Ito cells might be related to IR injury. In conclusion, ET-1 was associated with IR injury and TAK-044 reduced but did not affect hepatocyte DNA synthesis after partial hepatectomy.

Animals↗