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Hepatic pyruvate metabolism during liver regeneration after partial hepatectomy in the rat.

Hepatic pyruvate kinase (PK) and pyruvate dehydrogenase (PDHa) specific activities were decreased after partial hepatectomy or sham operation. The decreases were more marked and sustained after partial hepatectomy. These activity changes ensure that hepatic carbon flux after partial hepatectomy is predominantly in the direction of gluconeogenesis. The decrease in PK specific activity observed after partial hepatectomy was associated with a decreased PK activation ratio (activity measured at 0.15 mM PEP: activity measured at 5.0 mM PEP), and hepatic concentrations of PEP were increased. The low hepatic PDHa activity observed at the first day after partial hepatectomy occurred concomitantly with an increased fatty acid concentration. PDHa activity increased after inhibition of lipolysis. The results indicate that carbohydrate utilization is unimportant for hepatic energy supply during liver regeneration. There was no evidence that the control of PK or PDH in the regenerative liver after partial hepatectomy differed from that observed in the liver of the unoperated rat.

Animals↗

Hepatectomy in patients with nonuremic minimal renal failure.

In this study, the perioperative management and short-term outcome of hepatectomy were evaluated in patients with nonuremic minimal renal failure to assess the safety of hepatectomy in such patients. Ninety-one patients who underwent hepatectomy were retrospectively divided into two groups based on their creatinine clearance (Ccr) values: a group with Ccr values >or=50 but <100 ml/min (group 1; n = 77) and a group with Ccr values of >or=20 to <50 ml/min (group 2; n = 14). Preoperative patient characteristics, intraoperative parameters (including operation time and blood loss), and postoperative management and complications were evaluated. The preoperative evaluation showed no differences in liver function between the two groups, and there were no statistically significant differences between the two groups in intraoperative blood loss (522 ml in group 1 and 806 ml in group 2) or intraoperative urine volume (1.01 ml/kg per hour in group 1 and 0.75 ml/kg per hour in group 2). The difference between the two groups in postoperative complications was not statistically significant. None of the patients in group 2 required dialysis therapy, and no patients died as a result of hepatectomy or hepatectomy-related causes. Adequate indications, appropriate operative procedures, and perioperative management can enable hepatectomy to be performed safely in patients with nonuremic minimal renal failure.

Aged↗

Involvement of natural killer T cells and granulocytes in the inflammation induced by partial hepatectomy.

BACKGROUND/AIMS: Natural killer T (NKT) cells are present in the liver of mice. We examined whether NKT cells and other leukocytes were associated with hepatic inflammation after partial hepatectomy. METHODS: Approximately 70% of the liver was removed from mice using the method described by Higgins and Anderson. RESULTS: Partial hepatectomy induced the expansion of NKT cells in the liver and the elevation of transaminase. These responses were completely suppressed by the administration of tacrolimus. NKT cell-deficient mice showed a decreased level of transaminase after partial hepatectomy. Perforin (-/-) mice showed an elevation of transaminase while B6-gld/gld mice (Fas ligand-) showed a decreased elevation of transaminase. In TAP-1(-/-) mice which lacked CD8+ cytotoxic T cells, inflammation remained at a normal level after partial hepatectomy. Since NKT cell-deficient mice showed up to 50% decrease in the level of inflammation, we examined the association of other leukocytes with the remaining inflammation. The number and proportion of granulocytes were increased by partial hepatectomy. CONCLUSIONS: Both NKT cells and granulocytes participated in the hepatic inflammation after partial hepatectomy. The function of NKT cells, but not of granulocytes, was found to be sensitive to the immunosuppressive effect of tacrolimus.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Remnant liver injury after hepatectomy with the pringle maneuver and its inhibition by an iNOS inhibitor (ONO-1714) in a pig model.

BACKGROUND: Although hepatectomy is often performed with the Pringle maneuver, the problem of remnant liver injury is not fully solved. We examined the remnant liver injury of hepatectomy under the Pringle maneuver and its relation to inducible nitric oxide synthase (iNOS) in a pig hepatectomy model. MATERIALS AND METHODS: Pigs were subjected to a total of eight Pringle maneuvers followed by re-perfusion. The pigs were divided into the following three groups: Control group; only Pringle maneuver, liver resection (LR) group; hepatectomy under the Pringle maneuver, and ONO group; and hepatectomy under the Pringle maneuver with an iNOS inhibitor (ONO-1714). We investigated the changes in serum aminotransferase (AST), lactate dehydrogenase (LDH), NO(2)(-)+NO(3)(-) (NOx), the hepatic tissue blood flow (HTBF), the cellular distribution of endothelial and inducible nitric oxide synthase, nitrotyrosine, infiltration of neutrophils, and thrombocyte-thrombi by immunohistochemistry. RESULTS: The serum AST, LDH, NOx levels in the LR group were significantly higher than those in the Control group. The formation of iNOS, nitrotyrosine, thrombocyte-thrombi, and infiltration of neutrophils were recognized in the LR group. These findings were inhibited in the ONO group. CONCLUSIONS: These results indicate that remnant liver injury appeared after hepatectomy with the Pringle maneuver. iNOS was involved in these injuries and the iNOS inhibitor attenuated the injury.

Amidines↗

Jejunectomy can reduce excessively elevated portal pressure after major hepatectomy in beagle dogs.

A number of factors can lead to the life-threatening liver dysfunction in the aftermath of an extended hepatectomy. Prominent among them is the high portal pressure induced by the concentrated flow of the entire stream of portal blood toward the small remnant liver. Twelve beagle dogs were randomly divided into group A (n=6, 70% hepatectomy) and group B (n=6, 70% hepatectomy after jejunectomy). Three dogs in each group were euthanized at 1 or 4 weeks after the operation and examined to evaluate hemodynamic changes, liver functions, and liver histology. One hour after the hepatectomy, the animals in group B exhibited a significantly lower portal pressure (P=0.002) and significantly higher hepatic arterial flow (P=0.004) than the animals in group A. As more time passed, the total hepatic flow and hepatic tissue flow both rose up to levels significantly higher than those in group A (P=0.037 and P=0.025, respectively). The alkaline phosphatase, total protein, albumin, and anti-thrombin III were all significantly better in group B than in group A on the 1st post-operative day. Liver specimens biopsied at 1 h after the hepatectomy showed significantly more swelling of the hepatocytes in group A than in group B. In addition, an immunohistochemical study using the TUNEL method for liver biopsy on the seventh post-operative day revealed numerous positive cells in group A but few in group B. Our results suggest that the portal pressure control by the enterectomy can forestall dysfunction of the remnant liver after extended hepatectomy, especially during the early post-operative period.

Animals↗

Regrowth of the rat biliary tree after 70% partial hepatectomy is coupled to increased secretin-induced ductal secretion.

BACKGROUND & AIMS: After partial hepatectomy, liver regeneration occurs with the return of hepatocyte mass to normal, Limited data exist regarding the renewal of the biliary tree after partial hepatectomy. This study tested the hypothesis that, after partial hepatectomy, the biliary tree regenerates by proliferation of the remaining cholangiocytes, leading to an increase in secretin-induced ductal bile secretion. METHODS: After 70% partial hepatectomy, cholangiocyte proliferation was assessed in situ by morphometric analysis and In vitro by measurement of 3H-thymidine incorporation. Ductal secretion was estimated by measurement of secretin receptor gene expression and adenosine 3',5'-cyclic monophosphate (cAMP) levels in vitro and by the effect of secretin on ductal bile secretion in vivo. RESULTS: DNA synthesis was undetectable in control cholangiocytes, increased and peaked at day 3 after partial hepatectomy, and returned to normal by day 28. Morphometric analysis showed regrowth of the biliary tree beginning at day 1 with restoration by day 10. The expression of secretin receptor gene and secretin-induced cAMP levels and secretin-induced bicarbonate-rich choleresis increased during the period of bile duct renewal. CONCLUSIONS: After partial hepatectomy, the increase in secretin-induced ductal bile secretion observed during bile duct renewal results from proliferation of remaining cholangiocytes.

Animals↗

[Clinical study of 437 consecutive hepatectomies].

BACKGROUND: The aim of this prospective study was to analyze the risk of liver resection in unselected patients. PATIENTS AND METHOD: From 1990 to 2000, 437 consecutive hepatectomies were performed in our center. Most frequent indications were liver metastases (n = 288), hepatocellular carcinoma (n = 62), Klatskin tumor (n = 17), gallblader carcinoma (n = 139) and other malignant tumors (n = 6). The indication was a benign tumor in 51 patients. In 357 cases the liver parenchyma was normal, 51 patients had an underlying cirrhosis and 17 patients had an obstructive jaundice. RESULTS: Overall mortality was 3.6% (15 cases). Mortality in benign tumors was lacking. The prevalence of postoperative complications was 43.9%, which was mainly influenced by malignancy (46.9% vs 21.6%, p = 0.001) and type of tumor (Klastkin tumor, p # 0.001). Major liver resection (p < 0.001), blood transfusion (p < 0.001), age over 60 years (p = 0.001) and the type of hepatectomy (p < 0.001) also increased significantly the morbidity. The prevalence of biliary fistula was 11.2%, which was mainly related to the type of hepatectomy (major hepatectomy; p = 0.002) and a biliary-enteric anastomosis (p < 0.001). The prevalence of hepatic insufficiency was 3.6%, and chief risk factors for its development were underlying liver disease and major liver resection (p = 0.017). CONCLUSIONS: Mortality after hepatectomy in experienced centers is low. Morbidity is mainly related to the amount of parenchyma resected, type of hepatectomy, underlying liver disease and associated procedures. Liver resection should be performed preferentially in centers with high volume by specialized surgeons.

Aged↗

Laparoscopic partial hepatectomy and left lateral segmentectomy: technique and results of a clinical series.

BACKGROUND: Technical difficulties have impeded the development of laparoscopic hepatectomy. This article describes a new technique for performing partial hepatectomy and left lateral segmentectomy by means of laparoscopy, and the results in a series of 11 consecutive patients are reported. METHODS: A microwave tissue coagulator is used in combination with an ultrasonic surgical aspirator to divide hepatic parenchyma without pneumoperitoneum. Branched vessels and ducts are clipped and transected. The largest vessels were suture ligated in some cases. The endoscopic linear stapler was used to transect the left hepatic vein for left lateral segmentectomy. The resected liver was maneuvered into a specimen bag and removed. The argon beam coagulator was used to secure hemostasis of the plane of transection. RESULTS: Eleven patients underwent laparoscopic hepatic resection. Indications included isolated metastatic lesion, hepatocellular carcinoma, hemangioma, Wilson's disease, and hemochromatosis. Three patients underwent left lateral segmentectomy, and eight underwent partial hepatectomy. Ten procedures were performed uneventfully; one patient required conversion to open hepatectomy because of excessive bleeding. Notable differences were seen in blood loss compared with open hepatectomy, and no operative complications occurred. Postoperative pain was minimal. CONCLUSIONS: The laparoscopic hepatectomy, especially partial or left lateral segmentectomy, appears to be a viable surgical alternative in selected cases.

Adolescent↗

Epidermal growth factor is decreased in liver of rats with biliary cirrhosis but does not act as paracrine growth factor immediately after hepatectomy.

BACKGROUND/AIMS: Epidermal growth factor, a potent mitogen for hepatocytes and cholangiocytes, is thought to act as an immediate-early gene after partial hepatectomy. Since regeneration is impaired in cirrhosis, we explored the expression of epidermal growth factor in cirrhotic rat liver immediately after partial hepatectomy. METHODS: Cirrhosis was induced by bile duct ligation (n=21); sham-operated animals served as controls (n=21). Twenty-five days after initial surgery animals were subjected to 70% partial hepatectomy or sham operation; the liver was sampled before surgery and 20, 40 and 90 min thereafter. Epidermal growth factor mRNA levels were assessed by quantitative reverse transcription polymerase chain reaction. Protein expression was estimated by immunohistochemistry using a polyclonal antibody against epidermal growth factor. RESULTS: Before hepatectomy, epidermal growth factor mRNA averaged 70.3+/-39.9 pg/microg of total RNA in controls; this was markedly decreased to 21.9+/-12.7 pg/microg RNA in bile duct ligation (p<0.01). Epidermal growth factor mRNA did not increase after partial hepatectomy in either group, with the exception of sham-operated controls. Immunohistochemistry revealed that partial hepatectomy had no effect on epidermal growth factor expression. Hepatocytes showed uniformly cytosolic epidermal growth factor in controls, while in bile duct ligation immunostaining was faint or absent. Cholangiocytes exhibited a strong cytosolic staining in all experimental groups. CONCLUSIONS: The present study shows that epidermal growth factor is reduced in the cirrhotic liver. This could contribute to the loss of parenchymal liver tissue observed in cirrhosis. The lack of up-regulation after PH sheds doubt on the role of epidermal growth factor as an immediate-early gene in hepatic regeneration. Further, we demonstrate that epidermal growth factor accumulates in cholangiocytes. This observation is strong evidence for involvement of the mitogen epidermal growth factor in the proliferation of bile ducts during cirrhogenesis.

Animals↗

Expression of messenger RNA for liver functions following 70% and 90% hepatectomy.

AIMS/METHODS: The effect of moderate and severe reduction of the functional liver mass on gene expression for liver functions was studied in rats following 70% and 90% hepatectomy. At intervals up to 24 h after operation rats were killed and RNA was extracted from the remaining liver tissue. By slot-blot hybridization mRNA steady-state levels were determined for enzymes involved in metabolic 'liver-specific' functions, acute phase proteins, 'house-keeping', and growth-related proteins. Results were expressed as per cent of levels in a pool from fed control rats of the same gender and age. RESULTS: Among 'liver-specific' metabolic functions only expression of gluconeogenesis, represented by phosphoenol carboxykinase mRNA, was augmented initially, followed by a fall to very low values after 90% hepatectomy. The drug metabolizing system represented by CYP2B1/2 mRNA was reduced to half of the control values. Expression of urea synthesis, as reflected by carbamoylphosphate synthetase mRNA, showed a gradual decline after 90% hepatectomy, in contrast to rising levels of argininosuccinate lyase and arginase mRNA, possibly serving polyamine rather than urea synthesis. The mRNA level of the acute phase protein alpha 1-acid glycoprotein showed a smaller and later rise in 90% than in 70% hepatectomized rats, whereas that of alpha 2-macroglobulin only increased after 90% hepatectomy like the 'house-keeping' beta-actin mRNA. A rise in histone 3, which coincides with mitosis, was only seen after 70% hepatectomy, indicating that after 90% hepatectomy the response to growth-stimulating factors is weak or delayed, supported by a delayed rise in cyclin d and low levels of growth hormone receptor mRNA. CONCLUSIONS: It is concluded that attempts by gene regulation to adapt liver functions to a reduction of the liver mass depend on the amount of liver tissue lost. When the loss is nearly fatal, compensation for normal metabolic functions may be abandoned for efforts to regenerate, which, however, may be delayed or after all be too weak.

Actins↗

Organ blood flow after partial hepatectomy in rats: modification by endotoxin-neutralizing bactericidal/permeability-increasing protein (rBPI23).

BACKGROUND/AIM: Both maintenance of adequate perfusion and regeneration of the remnant liver are important in the recovery of liver function after partial hepatectomy. In previous experiments, we have shown that profound hypotension and liver injury can be attenuated by neutralizing endotoxins. The relative contribution of endotoxemia to changes in liver blood flow and blood flow to other major organs after partial hepatectomy is not known. The aim of this study was to examine the effect of endotoxin neutralization on individual organ blood flows including hepatic artery and splanchnic blood flow after experimental partial hepatectomy and its relation to liver cell proliferation. METHODS: Male Wistar rats underwent either two-thirds partial hepatectomy or sham operation. Treatment consisted of continuous infusion of recombinant N-terminal bactericidal/permeability-increasing protein (rBPI23) or control protein. At 4 h after surgery, organ blood flows were measured using the radiolabeled microsphere technique, and at 24 h, proliferation index in liver tissue was calculated. RESULTS: After partial hepatectomy, blood flows to virtually all organs were significantly lower as compared to values obtained in sham-operated rats. rBPI23 greatly improved hepatic artery flow (p<0.001) but not portal venous flow. These effects of rBPI23 on liver flow preceded an equally enhanced liver cell proliferation (p<0.01). Endotoxin neutralization led to significantly higher flows to some but not all splanchnic organs. Lung perfusion was significantly improved by rBPI23. CONCLUSIONS: Neutralization of endogenous endotoxins improves liver blood flow after partial hepatectomy and also periportal and pericentral liver cell proliferation. This proliferation effect may result from an increased hepatic artery flow. Lung, colon, spleen and pancreas flow but not kidney flow was greatly enhanced by rBPI23.

Animals↗

Parenchyma-preserving hepatectomy in the surgical treatment of hilar cholangiocarcinoma.

BACKGROUND: Although extended hepatic resection has been shown to improve prognosis by increasing the surgical curability rate in hilar cholangiocarcinoma, high surgical morbidity and mortality rates have been reported in patients with obstructive jaundice. Postoperative liver failure after hepatic resection in patients with obstructive jaundice has been shown to depend on the volume of the resected hepatic mass. The aim of this study was to evaluate the results of parenchyma-preserving hepatectomy in a surgical treatment for hilar cholangiocarcinoma. STUDY DESIGN: Ninety-three resected patients with hilar cholangiocarcinoma were included in this retrospective study. The resected patients were stratified into three groups: the extended hepatectomy (EXH) group (n = 66), the parenchyma-preserving hepatectomy (PPH) group (n = 14), and the local resection (LR) group (n = 13). The EXH group had undergone hepatectomy more extensive than hemihepatectomy, the PPH group had undergone hepatectomy less extensive than hemihepatectomy, and the LR group had undergone extrahepatic bile duct resection without hepatic resection. Surgical curability, defined by histologically confirmed negative surgical margins, surgical morbidity and mortality, and survival rates were compared among the three groups. The clinicopathologic factors were studied for prognostic value by univariate and multivariate analyses. RESULTS: Surgical curability of the PPH and EXH groups was better than that of the LR group. Fifty-four percent of patients in the LR group showed positive surgical margins at the hepatic stump of the bile duct, compared with 7% in the PPH group and 20% in the EXH groups (p < 0.01 for each comparison). Surgical morbidity was higher in the EXH group (48%) than in the LR group (8%) and the PPH group (14%) (p < 0.01 and p < 0.05, respectively). Postoperative hyperbilirubinemia occurred more frequently in the EXH group (29%) than in the LR and PPH groups (0% and 0%, respectively, p < 0.05 for each comparison). Survival rates after resection were significantly higher in patients who underwent hepatectomy, including PPH and EXH, than in patients who underwent LR, 29% versus 8% at 5 years, respectively (p < 0.05). But no significant difference in survival was found between the PPH and EXH groups. Univariate and multivariate analyses showed that significant prognostic factors for survival were resected margin, lymph nodal status, and vascular resection. CONCLUSIONS: In conclusion, PPH could obtain a curative resection and improve the outcomes for patients with hilar cholangiocarcinoma that is localized at the hepatic duct confluence who do not require vascular resection. PPH might bring about a beneficial effect in highly selected patients according to extent of cancer and high-risk patients with liver dysfunction.

Bile Duct Neoplasms↗

Ultrastructural zonal heterogeneity of hepatocytes and mitochondria within the hepatic acinus during liver regeneration after partial hepatectomy.

BACKGROUND INFORMATION: Partial hepatectomy (70%) induces cell proliferation until the original mass of the liver is restored. In the first 24 h after partial hepatectomy, drastic changes in the metabolism of the remaining liver have been shown to occur. To evaluate changes in hepatocyte ultrastructure within the hepatic acinus during the liver regenerative process, we investigated, by light and electron microscopy observations on specimens taken 0 h, 24 h and 96 h after partial hepatectomy, the hepatocyte structure and ultrastructure in the periportal and pericentral area of the hepatic acinus, with a particular emphasis on mitochondria ultrastructure. Moreover, some biochemical events that could affect the mitochondria ultrastructure and function were investigated. RESULTS: We found that, 24 h after partial hepatectomy, mitochondria with altered ultrastructure were preferentially localized in the periportal area. Periportal hepatocytes showed also an increase in the number of peroxisomes, free ribosomes, lysosomes and autophagosomes. Altered mitochondria showed swelling, an ultrastructural index of increased membrane permeability, a reduction in the number of cristae, and a rarefied, often vacuoled, matrix. Consistently, an increase in the mitochondrial oxidized/reduced glutathione ratio was found as well as calcium release from mitochondria in a manner inhibited by cyclosporin A. Interestingly, light and electron microscopy analysis showed that the hepatocytes in the periportal area were the cells with the major structural attributes to proliferate. At 96 h after partial hepatectomy, the preferential zonation of altered mitochondria was lost and the normal mitochondrial membrane permeability properties were restored. CONCLUSIONS: We suggest that 24 h after partial hepatectomy, a preferential zonation of altered mitochondria in the periportal hepatocytes could be involved in the changes of metabolic and functional heterogeneity of the hepatocytes within the hepatic acinus during the regenerative process.

Animals↗

Phosphatidylcholine metabolism in rat liver after partial hepatectomy. Evidence for increased activity and amount of CTP:phosphocholine cytidylyltransferase.

The effect of partial (70%) hepatectomy on phosphatidylcholine (PC) synthesis in rat liver was investigated during the first 4 post-operative days. Between 4 and 96 h after partial hepatectomy, the mass of PC increased from 30% to 80% of sham-operation values, being comparable with the restoration of total liver mass after partial hepatectomy. Relative to control (sham-operation), the incorporation in vivo of [3H]choline into PC was stimulated 2.6-fold at 22 h after partial hepatectomy. Moreover, CTP:phosphocholine cytidylyltransferase (EC 2.7.7.15) activity was significantly enhanced, and the pool size of phosphocholine decreased at 22 and 48 h after partial hepatectomy, whereas the activity of choline kinase (EC 2.7.1.32) was augmented at a later stage of liver regeneration (48 and 96 h). Stimulation of CTP:phosphocholine cytidylyltransferase activity by partial hepatectomy occurred in both the microsomal and cytosolic fractions. The stimulatory effect in the cytosolic fraction was mainly due to an increase in the number of enzyme molecules, as demonstrated by immunotitration of the amount of cytosolic cytidylyltransferase protein.

Animals↗

Liver regeneration after major hepatectomy for biliary cancer.

BACKGROUND: The aim of this study was to evaluate serial changes in liver volume after major hepatectomy for biliary cancer and to elucidate clinical factors influencing liver regeneration. METHODS: Serial changes in liver volume were determined, using computed tomography, in 81 patients with biliary cancer who underwent right hepatic lobectomy or more extensive liver resection with or without portal vein resection and/or pancreatoduodenectomy. Possible factors influencing liver regeneration were evaluated by univariate and multivariate analyses. RESULTS: The remnant mean(s.d.) liver volume was 41(8) per cent straight after hepatectomy. This increased rapidly to 59(9) per cent within 2 weeks, then increased more slowly, finally reaching a plateau at 74(12) per cent about 1 year after hepatectomy. The regeneration rate within the first 2 weeks was 16(8) cm3/day and was not related to the extent of posthepatectomy liver dysfunction. On multivariate analysis, the extent of liver resection (P < 0.001), body surface area (P = 0.02), combined portal vein resection (P = 0.024) and preoperative portal vein embolization (P = 0.047) were significantly associated with the liver regeneration rate within the first 2 weeks. In addition, body surface area (P < 0.001) and liver function expressed as plasma clearance rate of indocyanine green (P = 0.01) were significant determinants of final liver volume 1 year after hepatectomy. CONCLUSION: The liver regenerates rapidly in the first 2 weeks after major hepatectomy for biliary cancer. This early regeneration is influenced by four clinical factors. Thereafter, liver regeneration progresses slowly and stops when the liver is three-quarters of its original volume, approximately 6 months to 1 year after hepatectomy.

Adult↗

Preoperative hepatic venous embolization for partial hepatectomy combined with segmental resection of major hepatic vein.

BACKGROUND: Liver resection of segments VII and/or VIII sometimes requires segmental resection of the right hepatic vein in patients with liver tumours invading or located close to the hepatic vein. In this situation, hepatic vein reconstruction is thought to have an important role in the postoperative function of segment VI. This study investigated whether preoperative embolization of the major hepatic vein could obviate the need for hepatic vein reconstruction after cranial partial resection of the liver including the major hepatic vein trunk in a preclinical model. METHODS: Sixteen beagles were divided into two groups of eight: control group (hepatectomy alone) and hepatic venous embolization (HVE) group (hepatectomy after HVE). HVE was performed 2 weeks before hepatectomy. All dogs underwent resection of the cranial third of the left lateral liver lobe together with the major trunk of the left hepatic vein. Following hepatectomy, survival, histological features, portal venous pressure and serum aspartate aminotransferase (AST) levels were determined. RESULTS: Six control animals and seven in the HVE group were alive 1 week after hepatectomy. Immediately after hepatectomy, portal venous pressure was significantly higher in the control group compared with the HVE group (mean(s.d.) 14.0(1.1) versus 8.1(1.0) mmHg; P < 0.01). Histological examination of the remnant left lateral lobe demonstrated patchy parenchymal haemorrhage in the control group and normal parenchymal architecture in the HVE group. Peak AST levels were observed on day 1 in both groups and were significantly higher in the control group (mean(s.d.) 182(42) versus 67(40) units/l; P < 0.01). CONCLUSION: In this model, preoperative HVE facilitated interlobar venous collateral formation and minimized the untoward effects of segmental hepatic vein resection. This procedure may obviate the need for hepatic vein reconstruction after cranial partial liver resection including the major hepatic vein.

Alanine Transaminase↗

Beneficial effects of arterialization of the portal vein on extended hepatectomy.

BACKGROUND: Extended hepatectomy may result in postoperative liver failure. The aim of this study was to evaluate the effects of arterialization of the portal vein on oxygen supply, hepatic energy metabolism and liver regeneration after extended hepatectomy. METHODS: Portal haemodynamics were evaluated 0 or 10 days after arterialization of the portal vein in three experimental groups: 85 per cent partial hepatectomy, 85 per cent partial hepatectomy 10 days after arterialization of the portal vein and 85 per cent partial hepatectomy 10 days after ligation of the hepatic artery. Survival rates, weight of the regenerating liver, levels of adenine nucleotides and hepatic energy charge were assessed. RESULTS: Arterialization of the portal vein caused a significant increase in partial pressure of oxygen and oxygen saturation. Portal blood flow 10 days after arterialization was significantly increased. Survival rate and weight of the regenerating liver in the group with arterialization of the portal vein were significantly higher than those in the other two groups. The group with arterialization of the portal vein showed the highest levels of adenosine 5'-triphosphate. CONCLUSION: The increase in portal blood flow and oxygen supply produced by arterialization of the portal vein has beneficial effects on hepatic energy metabolism and liver regeneration, and leads to improved survival after experimental extended hepatectomy.

Animals↗

Liver gene regulation in rats following both 70 or 90% hepatectomy and endotoxin treatment.

BACKGROUND: The metabolic state effect of liver failure on liver gene regulation was evaluated in a rat model. METHODS: Following 70 or 90% hepatectomy and lipopolysaccharide or vehicle treatment at intervals up to 24 h, the liver remnants were analyzed for mRNA levels for acute-phase, liver-specific and growth-related proteins. RESULTS: After 70% hepatectomy mRNA for alpha 1-acid glycoprotein, alpha 2-macroglobulin, thiostatin and fibrinogen, haptoglobin increased three- to sevenfold (P < 0.05), and mRNA for cyclin D and histone 3 increased seven- and 15-fold (P < 0.05), respectively. After lipopolysaccharide injection and 70% hepatectomy were done, mRNA for acute-phase proteins raised significantly (P < 0.05), more to five to 20-fold, while mRNA for growth-related proteins raised significantly (P < 0.05) less to three- to fourfold. After 90% hepatectomy, acute-phase protein mRNA increased five- to ninefold (P < 0.05) more than after 70% hepatectomy, while mRNA for histone 3 and cyclin D did not increase within 24 h, which indicates a delayed growth after 90% hepatectomy. In 90% of hepatectomized rats treated with lipopolysaccharide, acute-phase protein mRNA raised three- to sixfold (P < 0.05) less than after vehicle treatment. CONCLUSION: In endotoxemia from liver failure, the synthesis of acute-phase proteins is upregulated by gene regulation at the expense of that for regeneration, which may be an appropriate response for immediate survival. In severe liver failure, endotoxin may interfere with the appropriate gene regulation.

Acute-Phase Proteins↗