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PubMed1991

[Effect of glucagon and insulin on the histochemical and functional alterations in the Langerhans islands after hepatectomy in dogs].

Changes of Langerhans islands after 40% hepatectomy, and effects of GI therapy on the islets were investigated in dogs. In control group, one week and four weeks after the hepatectomy, ivGTT was examined followed by a blood sampling from the portal vein to measure the changes of glucose, insulin and glucagon, and areal changes of the islets were measured. In GI group, the same experiment was done with added GI therapy after operation. The following results were obtained. 1) In control group, portal plasma insulin level and insulin response were decreased one week after surgery, and sizes of islets were enlarged four weeks after surgery. 2) In GI group, there were no decrease in portal plasma insulin level and insulin response one week after surgery, and no enlargement of the sizes of the islets four weeks after surgery. 3) Changes in glucagon level and glucagon response were same as those of insulin, glucose level and these response. There was no difference between the two groups. 4) According to these observation, glucagon and insulin are exhausted one week after hepatectomy in dogs. It seems to be necessary to provide the dog with glucagon and insulin after hepatectomy.

Animals↗
PubMed1991

[Inhibition of hepatic DNA synthesis after partial hepatectomy in the rats with obstructive jaundice with special reference to the enhancement of hepatic protein synthesis].

We studied the liver regeneration after partial (68%) hepatectomy in rats with obstructive jaundice followed by the relief of obstruction. Rats received bile duct ligation, then 5 or 14 days later choledocho-duodenostomy was performed. Partial hepatectomy was done at various intervals after the relief of obstruction. DNA synthesis of the regenerating liver, hepatic protein synthesis and mitochondrial swelling induced by exogenous phospholipase A2 (PLA2) were determined. Hepatic DNA synthesis was significantly inhibited in obstructive jaundiced rats compared to controls. While the inhibition disappeared 5 days after the relief of obstruction in 5-day-obstructed group, it was still detectable as late as 21 days after the drainage in 14-day-obstructed group. Hepatic protein synthesis was markedly increased by obstructive jaundice, and this increase continued until 10 days after drainage in 14-day-obstructed group. Partial hepatectomy also increased the hepatic protein synthesis significantly in normal rats, but failed to show any significant changes in obstructive jaundiced rats. Any difference could not be found in PLA2-induced hepatic mitochondrial swelling between obstructive jaundiced rats and normal rats. We concluded the preceding energy-requiring responses in obstructive jaundiced liver resulted in the reduction of hepatic DNA synthesis and in the lack of additional increase of hepatic protein synthesis as the responses to a further insult of partial hepatectomy.

Animals↗
PubMed1990

Hemodynamic changes after hepatectomy in rats studied with radioactive microspheres.

It has been difficult to measure hepatic arterial blood flow and portal venous flow simultaneously, especially in small animals. Radioactive microspheres were used in this experiment to quantitate splanchnic hemodynamics after hepatectomy in rats. With a reference sample technique, a certain amount of radioactive microspheres was injected into the left ventricle. The reference sample was withdrawn from the femoral artery at a constant rate. The animal was killed with a bolus of saturated KCl. The kidneys and splanchnic organs were removed and weighed. The radioactivity of each organ was determined using a gamma scintillation counter. Organ blood flow was calculated by the following formula: [formula: see text] Immediately after partial hepatectomy, a decreased cardiac index from 32.31 +/- 10.12 to 23.44 +/- 3.21 ml/(min x 100g body weight) (p less than 0.05), decreased hepatic arterial blood flow from 0.40 +/- 0.12 to 0.33 +/- 0.03 ml/(min x g liver) (p less than 0.05), increased portal venous inflow from 0.90 +/- 0.30 to 2.20 +/- 0.26 ml/(min x g liver) (p less than 0.05) and increased total hepatic blood flow from 1.30 +/- 0.39 to 2.53 +/- 0.26 ml/(min x g liver) (p less than 0.005) were observed. With an intrasplenic injection of an additional amount of radioactive microspheres, the ratio of lung/(lung + liver) radioactivities indicated the degree of portal systemic shunt (PSS). Though the portal pressure was elevated after hepatectomy (8.80 +/- 0.7 vs 11.9 +/- 1.7 cm H2O, p greater than 0.05), the extent of PSS was negligible (0.02 +/- 0.01% vs 0.03 +/- 0.01%, p greater than 0.05). The radioactive microspheres with the reference sample technique is a simple, rapid, reliable and reproducible method for investigating the hemodynamic changes following partial hepatectomy.

Animals↗
PubMed1991

Partial hepatectomy for Caroli's syndrome. Report of two patients with long-term follow-up.

Caroli's syndrome comprises cystic dilatations of the intrahepatic bile ducts, which may be focal or diffuse. Partial hepatectomy, when possible, is the best current treatment. We report on two patients with Caroli's syndrome confined to one side of the liver, who were subjected to partial hepatectomy. Both patients had a previous history of biliary tract surgery. Transhepatic percutaneous cholangiography and abdominal CT scan were helpful in establishing the diagnosis and the extent of the disease. After hepatectomy, one patient developed an abdominal abscess that required surgical drainage, the other developed persistent fever, which resolved spontaneously. Both patients are asymptomatic three and five years post-hepatectomy, respectively, and there is no clinical evidence of recurrence of the disease. The diagnostic work-up and therapeutic choices for this rare entity are discussed.

Adolescent↗
PubMed1990

Transforming growth factor receptors in liver regeneration following partial hepatectomy in the rat.

Transforming growth factors alpha and beta (TGF-alpha and TGF-beta) are produced in the liver and appear to play an important role in the regulation of hepatic growth. We investigated changes in receptors for these polypeptide growth factors in regenerating liver after partial hepatectomy in the rat with comparisons to livers from normal and sham-operated animals. In normal rats, binding of 125I-epidermal growth factor (EGF) to liver membranes was fully and competitively displaced by TGF-alpha, indicating that these two growth factors share similar sites on the same hepatic receptor. Scatchard analyses revealed that EGF receptors bound EGF with 4- to 8-fold higher affinity than TGF-alpha. Following partial hepatectomy or sham operation, EGF/TGF-alpha receptor number decreased by 25, 40, and 55% at 12, 24, and 72 h, respectively. In all cases. Scatchard analysis obtained with EGF yielded a linear plot indicating a single population of binding sites with a dissociation constant (Kd) of approximately 0.9 nM. Scatchard analysis of TGF-beta binding showed that liver membranes from sham-operated and normal rats express binding sites with a Kd of approximately 35 pM. In contrast, membranes obtained from 12-, 24-, and 72-h regenerating livers were altered in a manner consistent with uncovering or appearance of a higher affinity site. Affinity labeling of liver plasma membranes with 125I-TGF-beta revealed two predominant proteins with Mr 85,000 and 66,000. In unfractionated membrane preparations, two other proteins with Mr 105,000 and approximately 150,000 were seen. Following partial hepatectomy the major change in affinity-labeled proteins was a small (10-25%) but consistent decrease in the Mr 85,000 species. These results show that receptors for TGF-alpha and TGF-beta are modulated after partial hepatectomy, a further indication that these polypeptides may have an important role in liver regeneration.

Animals↗
PubMed1990

Ileocolectomy enhances the regenerative response after partial hepatectomy in the pig.

Although portal blood has been shown to be more hepatotrophic than peripheral venous blood, the origin and nature of the factors responsible remain obscure. In this study the effect of partial ileocolectomy (IC) or partial ileal resection (I) on the regenerative response after 50% partial hepatectomy (PH) in the pig was investigated using thymidine kinase activity and mitotic figures as indices of regeneration. IC with 50% partial hepatectomy resulted in a significantly greater regenerative response on the 3rd day than hepatectomy alone or hepatectomy plus partial I. Levels of plasma insulin were elevated after PH and I but not after IC, although there were no significant differences in levels of plasma glucagon or plasma glucose. Levels of aspartate amino-transferase were similar in all groups. These results extend previous data and suggest that the proximal colon may be the source of a regeneration inhibitory factor.

Animals↗
PubMed1990

[Hepatic hemodynamics after hepatectomy and the effect of administration of glucagon].

The effect of hepatectomy and administration of glucagon on hepatic hemodynamics were studied using mongrel dogs. The results were as follows: 1) Hepatic blood flow in the 70% hepatectomized dogs was significantly less than that in dogs subjected to sham operation or 40% hepatectomy. 2) Bolus injection of glucagon (10 micrograms/kg) increased blood flow in the hepatectomized dogs as well as that in the control dogs. The percentage increment, however, was significantly smaller in the 70% hepatectomized dogs, possibly due to little increase of portal vein blood flow. 3) Portal vein pressure and its resistance were significantly higher in the 70% hepatectomized dogs than in both the 40% hepatectomized dogs and the control dogs. 4) Although pre-sinusoidal resistance showed no significant difference among these three groups, post-sinusoidal resistance increased stepwise in the order of extent of hepatectomy. These results suggest that administration of glucagon after extended major hepatectomy is not so particularly effective in generating adequate hepatic tissue blood flow.

Animals↗
PubMed1989

[Effects of glucagon and insulin on poly(ADP-ribose) polymerase activity and blood ketone body ratio after partial hepatectomy in rats].

The effects of glucagon and insulin on liver nuclear poly(ADP-ribose) polymerase activity and blood ketone body ratio after rat partial (68%) hepatectomy were examined. Liver weight regeneration rate was enhanced by glucagon and insulin after 5th posthepatectomy day. The maximal value of poly(ADP-ribose) polymerase activity without glucagon and insulin was revealed as 368 +/- 64 pmole/mg/min on 5 days after the hepatectomy. In contrast, the enzyme activity with glucagon and insulin reached to the peak value as 253 +/- 42 pmole/mg/min on 2 days after the hepatectomy. The amounts of DNA per nuclear protein showed similar changes with the changes of poly (ADP-ribose) polymerase activity after the hepatectomy. Blood ketone body ratio showed almost similar changes in both groups, except transitional decrease in the group without glucagon and insulin on 5th postoperative day. It is suggested that, to promote remnant liver regeneration, the combined therapy of glucagon and insulin may act directly to nucleic acid metabolism through the changes of poly(ADP-ribose) polymerase activity and preserve energy charge level by the suppression of NAD consumption by massive poly(ADP-ribose) formation.

Animals↗
PubMed1989

Repeat hepatectomy for recurrent malignant tumors of the liver.

The results of 34 repeat hepatectomies for recurrent malignant tumors of the liver in 28 patients are reported herein. There was no operative mortality, and the morbidity rate was 15 per cent. No instances of postoperative hepatic insufficiency were observed. Only five of the repeat hepatectomies were extensive (three or more hepatic segments). Thirteen resections were performed upon 11 patients for recurrent hepatocellular carcinoma. Four of these patients are still alive, one patient with a known recurrence (a mean survival time of 33 months with a range of four to 54 months). Ten resections were performed upon nine patients for recurrent metastases from the colon and rectum. Five of these patients are alive, four without apparent recurrence (a mean survival time of 13 months and a range of one to 35 months). Eleven resections were performed upon eight patients for recurrent miscellaneous malignant tumors, and four patients are alive, of whom three have a recurrence. The results of this study demonstrate that some patients benefit from repeat hepatectomy for recurrence of malignant hepatic tumors. Repeat hepatectomy is technically highly feasible. Economic hepatic resection with a sound oncologic basis (segmentectomy) is the operation of choice.

Adolescent↗
PubMed1989

Stimulation of protooncogene expression by partial hepatectomy is not tissue-specific.

We have characterized the early protooncogene response and the later cell proliferative response in the kidneys and livers of normal rats cross-circulated with partially hepatectomized animals. Increase c-myc and C-Ha-ras expression was observed in the kidneys of totally hepatectomized rats, as well as those of their cross-circulated partners. This indicates that the initial response to hepatectomy is not organ-specific, although the later DNA synthetic response of the kidney is only approximately one-tenth that of regenerating liver. Expression of c-myc and c-Ha-ras is dramatically increased in the livers of both hepatectomized and nonhepatectomized, parabiotic (cross-circulated) rats within 1 hr of partial hepatectomy, confirming the presence of a circulating factor which stimulates protooncogene expression early in regeneration. DNA synthesis was also stimulated in the livers of the cross-circulated animals between 20 and 26 hr following hepatectomy, but only to a level one-eighth that of the livers of hepatectomized animals. Normal rats cross-circulated with totally hepatectomized animals also demonstrated an early increase in hepatic c-myc and c-Ha-ras expression, indicating that regeneration must be stimulated by an extrahepatic signal. Our data suggest that the early increase in protooncogene expression is a non-organ-specific response to partial hepatectomy which does not insure subsequent cellular proliferation. The organ specificity of liver regeneration must involve an event separate from the early stimulation of protooncogene expression.

Animals↗
PubMed1989

Stimulated rat liver mitochondrial biogenesis after partial hepatectomy.

In order to elucidate the response of mitochondria to the increase in cellular energy demand after hepatectomy, we have examined the effects of partial hepatectomy and hepatic artery ligation on the energy-transducing system of rat liver mitochondria. Specific content of DNA in the mitochondria increased on the first day after the hepatectomy and reached 150% of the original value. Oxidative phosphorylation capacity of the mitochondria started to increase on the first postoperative day. In contrast, specific enzymic activities, specific cytochrome contents, and subunit contents of the energy-transducing complexes in the isolated mitochondria were significantly increased only from the second postoperative day. The ligation of the hepatic artery did not inhibit the amplification of the mitochondrial function. The immunostain for ubiquinol-cytochrome c oxidoreductase was increased predominantly in the portal area of the hepatic lobules of the hepatectomized rats. These results suggest that enhancement of the mitochondrial oxidative phosphorylation system after hepatectomy is based on the increase of the amount of the complexes in the inner membrane, which is closely related to replication of mitochondrial DNA, and that the blood supply from the hepatic artery is not an important factor in the mitochondrial amplification in rats.

Animals↗
PubMed1986

[Role of blood flow in acute gastric lesion after hepatectomy and effect of prostaglandin I2 and H2-receptor antagonist].

In order to investigate the cause of gastric mucosal lesion following hepatectomy, changes of gastric, pancreatic and femoral arterial blood flow were measured in 70% hepatectomized rabbits. Following administration of 0.5 microgram/kg of GRP, gastric blood flow increased to 120% of the basal level in the controls, but reached to only 107% of the basal level in the hepatectomized rabbits. Following hemorrhage of 10% of the total blood volume seven days after hepatectomy, blood flow decreased to 55% of the basal level in the stomach, 57% in the pancreas and 76% in the femoral artery. Although pancreatic blood flow recovered to 81% of the basal level, gastric blood flow remained low, 59% of the basal level, suggesting poor recovery of gastric blood flow as compared to pancreatic blood flow. Administration of PGI2 and ranitidine in hepatectomized rabbits with hemorrhage conferred a considerable degree of recovery of gastric blood flow in the PGI2 group (from 56% to 80%) and in the ranitidine group (from 52% to 72%). Thus, disturbance of reaction and poor recovery of gastric blood flow following hemorrhage were indicated as important causes of acute gastric mucosal lesion associated with hepatectomy. Both PGI2 and ranitidine appeared to be effective for the maintenance of gastric blood flow after hepatectomy.

Animals↗
PubMed1985

[Hepatectomy after transcatheter arterial embolization (TAE) for hepatocellular carcinomas].

Subjects of this study were 26 patients with hepatocellular carcinoma who underwent hepatectomy after TAE. They did not develop serious complications due to TAE. A suitable interval between TAE and the planned hepatectomy was about one month, based on AFP levels and the recovery of liver functions. Hepatic arteriography after TAE was useful to observe changes of the blood flow into the liver and the carcinoma, as well as to find intrahepatic metastases. It is also necessary for making final decisions on the strategy of the hepatectomy. The effects of TAE greatly depended on patterns of arterial blood feeding. When the tumor was less than 5 cm in diameter, had a capsule, and was fed by a single artery the necrotic rate was high. TAE was effective in intrahepatic metastases 0.5 cm or more in diameter, which were detectable by hepatic arteriography. TAE had little effect on intrahepatic metastases less than 0.5 cm in diameter, on intracapsular or extracapsular invasion, or on tumor embolus. For tumor embolus in the portal vein, since TAE and hepatectomy give poor results, other methods should be considered.

Adult↗
PubMed1985

[Cyclic AMP- and ATP-mediated stimulation of DNA synthesis following partial hepatectomy by prostaglandin-E1 in D-galactosamine injured liver].

D-galactosamine (D-gal) damaged rats were infused with Prostaglandin E1 (PGE1) through a peripheral vein for 40 min. before and after partial hepatectomy. DNA synthesis following 68% partial hepatectomy was severely inhibited by the pretreatment of D-galactosamine. PGE1 infusion (0.5, 1.0 microgram/kg/min) enhanced the DNA synthesis inhibited by D-gal 600 mg/kg significantly (p less than 0.01). After 20 min. of PGE1 infusion cyclic AMP levels of liver tissue was increased as compared with saline infusion in D-gal (600 mg/kg)-damaged rat (p less than 0.05). Also 20 min. and 3 hour after partial hepatectomy. ATP levels of liver tissue was enhanced in PGE1 treated group (p less than 0.05). However the doses of PGE1 infused in this investigation could not increase the hepatic tissue blood flow measured by hydrogen gas clearance method. These results suggest that PGE1 enhance DNA synthesis of injured liver after partial hepatectomy by the mechanism which PGE1 stimulate cyclic AMP production and increase ATP level in hepatic tissue.

Adenosine Triphosphate↗
PubMed1986

[Measurement of the portal blood flow in man by continuous local thermodilution method: II. Portal hemodynamics before and after hepatectomy].

We found that measurements of portal blood flow by continuous thermodilution were highly reproducible even after hepatectomy. Our subjects numbered 59 in all: In these patients having diseases of the liver and biliary tract, we studied portal hemodynamics during percutaneous transhepatic portography. Of these, 37 underwent hepatectomy. We chose 19 subjects from this group, and measured again both portal venous flow and portal venous pressure many times, continuing for 14 more days. In all 19 patients checked after hepatectomy, portal hemodynamics became hypodynamic, and this change was greater when the amount of liver resected was large. In 18 of these patients, hemodynamics started to improve after the 7th postoperative day. Changes in hemodynamics were not significantly different in patients with or without cirrhosis. In one patient who died of hepatic failure, the portal hypodynamic state did not improve. With this exception, in patients with major resections, portal venous flow per liver volume had increased after surgery and continued to increase. This was not true for patients with minor resections. Portal hemodynamics are important in the functioning and regeneration of the remaining liver, and it is necessary to understand and medically correct portal hemodynamics before and after hepatectomy.

Adult↗
PubMed1988

Binding parameters of rat liver nuclear receptors for T3 after partial hepatectomy or bilateral adrenalectomy and serum T4 and T3 levels.

Nuclear receptor affinity (Ka) and maximal binding capacity (MBC) for 3,5,3'-triiodothyronine (T3) in rat liver was estimated at 1, 12, 24, 48 and 120 hours after partial hepatectomy and 1, 24, 30, 40 and 120 hours after bilateral adrenalectomy and related to serum T4, T3 levels. Soluble T3 receptor fraction was prepared from purified rat liver nuclei and the values of Ka and MBC were calculated by Scatchard plot analysis from the saturation curves. As compared to sham operated rats a significant diminution in MBC for T3 (P less than 0.05) in the remaining about one third of liver tissue at 12, 24 and 48 hours after partial hepatectomy was observed. The thyroxine (T4) level in serum was diminished (with P ranging from less than 0.001 to less than 0.01) at 12, 24 and 48 hours after partial hepatectomy, while no changes in T3 serum level were found at all indicated time intervals. In contrast, no changes in Ka or MBC for T3 in rat liver nuclear receptor as well as in serum T4 and T3 levels were demonstrated 1, 24, 30, 40 and 120 hours after adrenalectomy. The data reflect an appreciable relation between nuclear receptor occupancy for T3 and serum T4 level after partial hepatectomy, serum T3 level and Ka for T3 of nuclear receptor remaining unchanged.

Adrenalectomy↗
PubMed1988

Cyclosporin A stimulates proliferation of the liver cells after partial hepatectomy in rats.

The effects of cyclosporin A (CyA) upon regeneration of the liver were studied in rats after partial hepatectomy. In group 1, a standard two-thirds hepatectomy was performed. In group 2, CyA, a dose of 10 milligrams per kilogram, was given orally one day prior to, on the day of the operation and 24 hours after hepatectomy. The liver weight restoration, histologic findings and mitotic activities of remnant livers and serum levels of aminotransferase, albumin, total bilirubin and creatinine values were examined from 24 hours to ten days after the operation. Treatment with CyA resulted in an increase of the mitotic activities of the hepatocytes, which were twice as high as those in the control group. This phenomenon coincided well with the regenerative rate of remnant livers, histologic factors, albumin synthesis and other biochemical parameters. Our results indicate that CyA has a stimulatory effect upon liver cell proliferation after partial hepatectomy in rats. The augmentative effect of CyA on liver regeneration is discussed.

Animals↗
PubMed1987

[Studies on adequate components and amounts of transfusion solution after hepatectomy from the viewpoint of the development of lung edema].

The purpose of this study was to evaluate the mechanism of development of lung edema and to determine adequate components and amounts of transfusion solution after major hepatic resection in normal and Dimethylnitrosamine (DMNA)-induced cirrhotic dogs. The dogs were administered maintenance dose (1-2 ml/kg/h) or large volumes (10-20 ml/kg/h) of lactated Ringer's solution (RL), 10% Dextrose or Dextran 40 (D40) after surgery. 1) In the groups transfused with maintenance dose or large volumes of RL, or large volumes of D40 after 80% and 70% hepatectomy in normal dogs and 40% hepatectomy in DMNA-induced cirrhotic dogs, the extravascular lung water (EVLW) increased with a high incidence of the development of lung edema. On the other hand, in the groups transfused with maintenance dose or large volumes of 10% Dextrose, or maintenance dose of D40, EVLW did not increase, thus preventing the development of lung edema. 2) The lower the functional reserve of the remaining liver and reticuloendothelial function, the more the volume of EVLW increased. The increments in plasma endotoxin titers through the spill over phenomenon, due to the decline of reticuloendothelial function after hepatectomy, caused an increase in the permeability of lung capillaries. Moreover, the decrease of colloid hydrostatic pressure gradient (CHPG) also caused an increase in EVLW. It is clear that both the permeability of lung capillaries and CHPG contribute to the development of lung edema after hepatectomy.

Animals↗