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Effect of the infusion of glucose, itralipid and nutramin on the initiation of rat liver regeneration after partial hepatectomy.

Rats were subjected to 67% hepatectomy and immediately after the operation were given a 4-hour infusion containing 5 ml saline solution, 28% glucose, 10% Intralipid, 8% glucose or 8% Nutramin. The rats were killed 18, 21, 24 and 30 h after partial hepatectomy. The effect of the tested solutions on the rate of liver regeneration was evaluated from changes in DNA specific activity and the mitotic activity of the hepatocytes. The infusion of 28% and 8% glucose markedly inhibited the onset of regeneration after partial hepatectomy. Nutramin likewise had an inhibitory effect, but not so pronounced as that of glucose. Conversely, the infusion of a lipid emulsion (Intralipid) and saline stimulated the initiation of liver regeneration compared with glucose and/or Nutramin. The possible mechanisms of the effect of infusion of the individual tested solutions on the onset of liver regeneration are discussed.

Amino Acids↗

Four new hepatectomy procedures for resection of the right hepatic vein and preservation of the inferior right hepatic vein.

Among the accessory hepatic veins, the thickest one is the IRHV and is a significant vessel in 20 to 24 per cent of the patients. In these patients, if the right hepatic vein is totally resected, the right posteroinferior area can be preserved with the IRHV. Four types of hepatectomies n which the IRHV was preserved were proposed and three of the four procedures were performed upon five patients. In these five operations, the hepatectomies were successfully performed and blood losses were from 1,020 to 3,200 milliliters. These operative procedures, which have not been described before, could widen the indication of hepatectomy in patients with reduced liver function and tumor involving the right hepatic vein. In order to perform these operative procedures successfully, intraoperative sonography is indispensable.

Adult↗

Effect of partial hepatectomy on experimental liver invasion by intraportally injected colon carcinoma cells in rats.

Two-third hepatectomy or sham operation was performed in BD IX rats immediately after intraportal injection of colon adenocarcinoma cells of the DHD-K12-TR strain. A dramatic increase in the incidence and growth of tumor cell colonies formed in the liver was observed in the partially hepatectomized as compared to sham-operated animals. Tumors formed in these conditions, developed in the liver parenchyma within less than 2 weeks and were macroscopically detectable at 1 month, without dissemination to other organs at this time and with little alteration of structural morphology of the liver. The model is particularly adequate for therapeutic assay on liver metastases, as, contrary to other models, it does not involve any drug that might interfere in the evaluation. The mechanism whereby partial hepatectomy is acting to enhance tumor take and growth is still unclear. A similar positive effect of hepatectomy on the growth of adenocarcinoma cells when these were grafted in female accessory glands excludes a simple mechanical cause and suggests the involvement of a circulating factor.

Adenocarcinoma↗

[Clinical and experimental studies on ligation of the draining vein in the remnant liver during hepatectomy].

In recent 8 years we experienced 6 cases of No. 7 and 8 segmentectomies in 140 hepatectomies. In 4 of them resection of the right hepatic vein (RHV) was unavoidable and two were released from RHV resection by using ultrasonic aspiration method. In the former cases non-cirrhotic patients had transient elevation of transaminases after surgery, while cirrhotic patients demonstrated severe liver dysfunction. The latter cases were uneventful after surgery. In the experimental study, the two groups of rats were made by Group-I (Gr-I) with only 40% hepatectomy and Group-II (Gr-II) in which the hepatic veins draining a remnant lobe were ligated after 40% hepatectomy. The remaining liver lobes with intact veins in Gr-I and Gr-II showed normal hepatic regeneration. However, the parenchyma without draining veins in Gr-II revealed severe congestion and necrosis and transaminases in Gr-II elevated significantly higher than Gr-I soon after operation. Thereafter, DNA synthesis of the hepatocytes with 3H-thymidine had a peak value before collateral vessel formation. Consequently, however, the hepatic volume of the vein-ligated region decreased considerably. Thus, clinical and experimental results suggest that the vein-ligated region can not be expected to share the liver function after hepatic lobectomy and hepatic failure may occur in the cirrhotic patients.

Animals↗

[A study of the effects of fresh frozen plasma to improve host defense against bacterial infection and levels of coagulation factors after hepatectomy].

Intraperitoneal infection and massive bleeding after hepatectomy often lead to liver failure. A possible cause of these complications may be the debasement of coagulation factors and opsonins in plasma after hepatectomy. The effects of fresh frozen plasma (FFP) to prevent these complications were investigated. 1) In the patients administered with more than 10 units/day of FFP after major hepatectomy, postoperative plasma opsonic activity was higher and the frequency of the intraperitoneal infection was lower than in the patients administered with smaller volume. In the former group, the activity of coagulation factors tended to increase postoperatively except for factor VII. But even the activity of factor VII was above critical level, and actually postoperative bleeding caused by coagulative insufficiency was not observed. 2) In the 70%-hepatectomized dogs, disappearance curve of intravenously injected Escherichia coli was biexponential. So two compartment model composed of circulating blood and phagocytic system was applied and velocity constants of the each phases of sequestration, reflux, and ingestion were calculated. The administration of FFP and opsonization of bacteria by normal plasma did not influence the phases of sequestration and reflux, but significantly accelerated the ingestion phase. The administration of FFP also increased survival rate after bacterial injection. These results suggest that FFP is effective on improving host defense against bacterial infection.

Aged↗

[Metabolic intensive care based on the hepatic mitochondrial redox in hepatectomy].

Intraoperative stress (ISS) in hepatectomy was quantified by the serial measurement of blood ketone body ratio (KBR) during operation. ISS was closely related with the decrease in the postoperative KBR and an enhanced postoperative catabolism. Postoperative urinary 3-methylhistidine level was positively and serum retinol binding protein level was negatively correlated with ISS. Intraoperative stress was closely linked with the postoperative metabolic abnormalities. A key stone in the postoperative management in hepatectomy is to elevate KBR. Utilization of energy substrate in the remnant liver is determined by the KBR level. When the KBR is maintained at higher than 0.7, glucose is predominantly utilized, while free fatty acids utilization increases according to the decrease in the KBR. KBR can be an index in the nutritional support after hepatectomy.

Hepatectomy↗

[Hepato-portal-splenic dynamics after hepatectomies].

The present study was performed to clarify the regeneration and splenic changes following hepatectomy. The processes were compared between the three classes (L greater than 50%, 30 less than M less than 50%, S less than 30%) categorized by the resection rate (%) calculated by CT scan in the 26 cirrhotics (LC) and 22 non-cirrhotics (N). Hepato-splenic volumes were serially measured by CT scan. The regenerative speed (cm3/day) of the remaining liver were significantly higher in the N group than LC and in the larger resection class. Liver functions tended to return to the initial levels behind the time of restoration of the liver volumes. The delay was partially caused by the posttransfusion hepatitis (PTH), which developed more frequently with an increase of fresh frozen plasma transfusion given. The changing pattern of splenic size was strongly regulated by the massiveness of hepatectomy. Newly developed posthepatectomy esophageal variceal ruptures were endoscopically determined in the 10% of the 129 late deaths after hepatectomies for hepatomas (1973-1987) with or without recurrences and its occurrence was found to be enhanced in the massive resection in the LC group ended with the poor regeneration of the liver and persistent postoperative splenic enlargement.

Esophageal and Gastric Varices↗

The organ distribution of [3H]endotoxin following partial hepatectomy.

3H-labeled endotoxin was intravenously injected into Wistar rats 24 hours following 70% hepatectomy and also into the normal rats. They were sacrificed 12 hours, 24 hours or 5 days after the injection. Microscopical autoradiography was performed on the rats' organs. The distribution of endotoxin in the organs was investigated by quantitatively measuring their radioactivity. Endotoxin was taken up mainly by Kupffer cells of the liver in all the groups. Endotoxin was observed also in macrophages of the spleen and the lung in all the groups. The amount of endotoxin per 1 g organ weight of the hepatectomized rat was significantly smaller in the liver, and significantly larger in the spleen, lung and blood (per 1 ml) than that of the control groups early after hepatectomy. These differences of the organ accumulation of endotoxin between groups diminished 5 days later. Deficient tolerance of the liver to endotoxin at the peak phase of regeneration following partial hepatectomy was suggested.

Animals↗

[Changes of plasma amino acid profiles following total hepatectomy under veno-veno bypass in dogs].

Patients with advanced liver disease demonstrate characteristic plasma amino acid abnormalities. The response of plasma amino acid patterns after liver transplantation in those patients is unknown. Mongrel dogs were subjected to two experimental models, that is, one is total hepatectomy under veno-veno bypass as an assumption of an hepatic phase in liver transplantation and the another is splenectomy as control. In control group, BCAA/AAA ratio rose gradually during operation. The levels of methionine, glycine and alanine were significantly lower at 4 hours. In hepatectomized dogs, BCAA/AAA ratio fell gradually after total hepatectomy. The levels of amino acids except BCAA were higher than preoperative value. Increase of alanine was the most remarkable early after total hepatectomy. It was derived not only from the lack of glucose-alanine cycle but also from increased synthesis due to degradation of the BCAA in muscle.

Amino Acids↗

Clearance of indocyanine green in dogs with partial hepatectomy, hepatic duct ligation, and passive hepatic congestion.

Clearance of 5 submaximal doses of indocyanine green (ICG) was measured in 5 dogs to determine the maximal removal rate (0.188 mg/kg of body weight/min) and Michaelis constant (Km, 1.25 mg/kg). From these results, 5 mg of ICG/kg of body weight was chosen on the basis of the recommendation that the dose should be at least 4 X Km to achieve sensitivity as a measure of hepatic function and independence from hepatic blood flow. Clearances of low (0.5 mg/kg) and high (5 mg/kg) doses of ICG were measured in 35 healthy dogs to determine reference values. Fractional disappearance was 15.1 +/- 10%/min for the low dose and 3.9 +/- 1%/min for the high dose; plasma half-life was 6.3 +/- 3.6 minutes and 19 +/- 4.8 minutes, respectively. The sensitivity of 2 doses of ICG was evaluated in dogs with 20% and 40% hepatectomy, nonhyperbilirubinemic obstructive cholestasis, or hepatic congestion; sham-operated dogs served as controls. Fractional disappearance and plasma half-life of ICG in the 40% hepatectomy and hepatic congestion groups were significantly different (P less than 0.05) from those in controls using both ICG doses, indicating that both doses were affected by hepatic perfusion, as well as hepatic mass. The fractional disappearance of the dye in the cholestasis group also differed significantly (P less than 0.05) from that of the controls at the high dose. Plasma clearance of both doses by dogs with 20% hepatectomy was not significantly different from that of controls.

Animals↗

Liver regeneration factor detected in human serum after partial hepatectomy.

We obtained blood sera from patients before and after partial hepatectomy, and estimated the activities of the sera in promoting DNA synthesis in a primary culture of rat hepatocytes. The stimulating activity in portal serum from patients without any postoperative complications increased significantly after liver resection; that in portal serum from patients with complications did not. The amount of stimulatory factor transported to the liver, calculated by use of the stimulating activity in portal serum and the portal blood flow, increased after partial hepatectomy. The maximum amount was correlated to the resection ratio (p less than 0.05) and seemed to be correlated to the increase in liver volume. These results suggest that a stimulatory factor or factors are present in portal serum after partial hepatectomy and that such a factor and portal blood flow are important in liver regeneration after surgery.

Animals↗

Hepatic regeneration following partial hepatectomy in mice infected with Schistosoma mansoni.

Signs of hepatic regenerative activity were detected by radioactive thymidine incorporation and cariometry in hepatic parenchymal cells of mice infected with 30 cercariae of Schistosoma mansoni for 10 weeks and then submitted to partial (30%) hepatectomy. The same methods failed to detect regeneration in mice submitted to partial hepatectomy, to S. mansoni infection or to sham operation, as well as in normal control mice. The stimulus required for hepatic regeneration in the mouse apparently needs to be strong, as was the case when the effects of partial hepatectomy were added to those of S. mansoni-induced lesions. These data show that extensive schistosomal lesions do not impede hepatic cell regeneration by the mouse.

Animals↗

[Regeneration of liver parenchyma and sinusoidal cells following partial hepatectomy].

Partial hepatectomy (30 percent of the liver weight) was performed in 225 female Wistar rats, ages 6 weeks, 6 and 9 months. The animals were sacrificed in intervals between 4 hours and 21 d after the operation. The automated microscopic image analysis after Simon et al. (1984) and histoautoradiography were utilized for evaluation of liver cell regeneration. Despite measurement of more than 1,000 cells per animal we were not able to confirm enlargement of hepatocytes as the first reaction to partial hepatectomy The number of liver cells per unit area increased whereas sinusoidal size remained rather constant, corresponding to a decrease in average cell size and in the standard deviation of cell area. The importance of binucleated hepatocytes in the process is emphasized. Measurement of the nucleoli and of the mean extinction values of liver cell nuclei as a measure of the DNA content did not provide any essentially new perspectives. The investigation did however emphasize the importance of the extent of the hepatic resection and the age of the experimental animals on the intensity and subsequent course of liver cell regeneration. Proliferation of the sinusoidal cells themselves after partial hepatectomy could not definitively be demonstrated to be age-dependent.

Age Factors↗

Alteration in binding of dexamethasone to glucocorticoid receptors in regenerating rat liver after partial hepatectomy.

Changes in binding of dexamethasone (9 alpha-fluoro-11 beta, 17 alpha, 21-trihydroxy-16 alpha-methylpregna-1,4-diene-3,20-dione) to its receptors in regenerating rat liver after 70% hepatectomy were examined. Specific receptors for dexamethasone in the liver remnants of adrenalectomized rats decreased significantly during the period of DNA synthesis after 70% hepatectomy; then, they increased to above the control values between Days 4 and 7 after partial hepatectomy and subsequently returned to the control values. During the period of DNA synthesis, decreased binding was observed in partially hepatectomized rats with or without adrenals, but later enhanced binding was not prominent in rats with adrenals.

Adrenal Glands↗

Differential mechanisms of increased alpha 1-fetoprotein production in rats following carbon tetrachloride injury and partial hepatectomy.

Possible differences in the mechanisms of increased alpha1-fetoprotein (AFP) production following carbon tetrachloride (CCl4) intoxication and partial hepatectomy were studied with 5-week-old rats at the time of sacrifice. The maximum level of serum AFP reached in 4 days after a single dose of CCl4 was much higher than that after partial hepatectomy, although the incorporation of [3H]thymidine into liver DNA increased nearly to the same extent by either of these treatments. In the remnant after partial hepatectomy, the DNA synthesis that was further accelerated by treatment with a lower dose of thioacetamide was not associated with any further increases of serum AFP levels. However, CCl4 given to partially hepatectomized rats had an additive effect on increased AFP levels. The increases of serum AFP concentrations in CCl4-injured rats had an additive effect on increased AFP levels. The increases of serum AFP concentrations in CCl4-injured rats were depressed by Mitomycin C given in vivo, whereas the increases in partially hepatectomized rats were not. Treatment with 8-azaguanine inhibited both increase of serum AFP levels, although the inhibition was much less or was insignificant in partially hepatectomized rats. These results suggest that existence of different underlying mechanisms of the increased AFP production for the two experimental conditions.

Animals↗

Intraoperative ultrasonic examination for hepatectomy.

Intraoperative ultrasonic examination (IUE) was performed on 118 patients who were laparotomized for hepatectomy with five types of specially designed real-time linear array transducers. Many lesions which were invisible and nonpalpable from the surface of the liver were present in 58% of patients. All these lesions were detected by IUE. Among 16 tumors in 13 patients, IUE demonstrated 11 tumor thrombi (69%). By angiography, definite and equivocal diagnosis was made only in six tumor thrombi. Systematic subsegmentectomy was performed in 41 cases. The new concept of partial hepatectomy was accomplished by IUE. IUE is an indispensable operative procedure for hepatectomy.

Carcinoma, Hepatocellular↗

[Some peculiarities of gene expression in inbred and hybrid rats under normal conditions and after partial hepatectomy].

The peculiarities of gene expression in line and hybrid rats in the normalcy and after partial hepatectomy were studied. It was shown that the relationship between the RNA synthesis rate in chromatin and RNA transport in the cytoplasm as well as the correlation between the RNA transport rate and the activity of the protein-synthesizing mechanism vary in animals with different genotypes. After partial hepatectomy the hybrids have their S-period of the cell cycle earlier than the line animals. The hybrids do not differ from the parental forms in the rate of RNA chromatin synthesis; however, the newly synthesized RNA of the hybrids in transported into the cytoplasm 5.7 and 5 times faster than that of the lines Vistar and August. The rapidly transported RNA of hybrids is likely to have a more prolonged life as compared to the line animals. After partial hepatectomy an activation of the whole gene expression system occurs. The differences in the gene expression system of hepatocytes of inbred and hybrid animals in the regenerating liver become less pronounced.

Animals↗

Transhepatic changes in insulin and glucagon following partial hepatectomy in the pig.

In this study, glucose levels decreased after partial hepatectomy in the pig. This was associated with a decrease in insulin and an increase in glucagon levels. An added dextrose infusion resulted in hyperglycemia and appropriate responses in insulin and glucagon. Insulin clearance remained unchanged and glucagon extraction by the liver was decreased after partial hepatectomy. Changes in insulin and glucagon after partial hepatectomy appear to be related to the changes in blood glucose rather than the regenerative process.

Animals↗