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PubMed1998

Plasma-kallikrein clearance during liver regeneration after partial hepatectomy in the rat.

AIMS/BACKGROUND: The liver clears circulating plasma-kallikrein through a receptor-mediated endocytosis process: an initial fast phase is followed by a slow exponential phase. METHODS: To determine whether the clearance rate of plasma-kallikrein is affected during liver regeneration, we perfused isolated rat livers with rat plasma-kallikrein (rPK) at 0, 1, 2, 3 and 7 days after partial hepatectomy or sham operation. RESULTS: Liver regeneration was followed by the expression of the proliferating-cell nuclear antigen (PCNA) labeling index. The serum concentration of alpha2-macroglobulin, an acute phase protein in rats, was measured. At day 1, the fast phase of rPK clearance rate increased in hepatectomized rats when compared with day 0 (4.9+/-0.4 and 3.7+/-0.4 mU/g liver min, p<0.05). However, at day 2, the rPK fast phase clearance rate dropped significantly (2.6+/-0.2, p<0.05), when compared with day 1. No difference was found among the sham groups at different days of hepatectomy. These changes seem to be independent of the acute phase reaction. The regenerative liver weight increased continuously during the observation period. PCNA expression increased significantly after hepatectomy, with maximal PCNA-labeling indices at days 1 and 2, declining thereafter. CONCLUSION: The rPK fast phase clearance rate changes during liver regeneration, with a zenith occurring when PCNA labeling index is maximal (day 1) and a nadir occurring at the mitotic phase (day 2).

Animals↗

PubMed1988

Upper abdomen: CT findings following partial hepatectomy.

The appearance on computed tomographic (CT) scans of the upper abdomen after partial hepatectomy is complex. The findings expected at CT should not be confused with those of surgical complications, such as abscess, biloma, or hematoma. The findings on CT scans and the records of 17 patients who had undergone partial hepatectomy for malignancy were reviewed. Operations included wedge resection, left medial and lateral segmentectomies, left lobectomy, right subsegmentectomy, right lobectomy, and extended right lobectomy (trisegmentectomy). When partial hepatectomy had been performed with no complications, findings at CT included a small region of low attenuation at the surgical margin, probably due to transient accumulation of blood and bile; a right pleural effusion; extraluminal gas; shift of abdominal organs; hepatic regeneration; and fat attenuation at the resection margin representing the omental patch placed at surgery. Findings associated with surgical complications--such as abscess, biloma, and hematoma--included large or high-attenuation perihepatic and subphrenic fluid collections that did not conform to the resection margin.

Adolescent↗

PubMed1991

Changes in portal blood flow consequent to partial hepatectomy: Doppler estimation.

Hemodynamic changes in portal blood flow were investigated in 56 patients with hepatic tumors who underwent partial hepatectomy. Portal flow was measured with a Doppler ultrasound system before, during, and after surgery. The portal flow of patients who underwent massive hepatectomy decreased intraoperatively. The portal flow per unit of cardiac output decreased in patients who underwent massive or major hepatectomy, patients with a cirrhotic liver, and patients who had a satisfactory postoperative course. Postoperatively, the portal flow in patients with a poor clinical outcome (multiple organ failure, hepatic failure, and cardiorespiratory failure) decreased significantly. Monitoring portal hemodynamic values appears to be useful in providing an index of "hepatic functional reserve." Adequate portal flow is essential for postoperative hepatic regeneration; changes in portal hemodynamic values may be directly related to the patient's ability to survive surgery and to regain or maintain normal liver function.

Adult↗

PubMed2005

NF-kappaB activation in Kupffer cells after partial hepatectomy.

The transcription factor nuclear factor-kappaB (NF-kappaB) is activated during liver regeneration after partial hepatectomy. However, the physiological role and cellular localization of NF-kappaB activation are unresolved. In this study, we used an adenoviral vector expressing a mutated form of IkappaBalpha to inhibit NF-kappaB activity during liver regeneration. After partial hepatectomy in mice, introduction of Ad5IkappaB, but not a control virus (Ad5GFP), resulted in increased liver injury and decreased hepatocyte proliferation. Hepatocyte apoptosis was not observed. To investigate the kinetics and cellular localization of NF-kappaB-induced transcription during liver regeneration, we generated a transgenic mouse expressing enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-kappaB cis elements (cis-NF-kappaB-EGFP). During liver regeneration, EGFP expression was detected within 12 h and was primarily located in Kupffer cells. Our data demonstrate that activation of NF-kappaB initially occurs in Kupffer cells after partial hepatectomy in mice.

Adenoviridae↗

PubMed1993

Hepatic intracellular pH during the prereplicative period following partial hepatectomy.

To investigate the hypothesis that the regenerating liver undergoes intracellular alkalinization during the prereplicative period, we measured intracellular pH (pHi) after partial hepatectomy in the rat. pHi was studied in livers from female Wistar rats perfused in situ with buffer containing HCO3-/CO2. The multiple indicator-dilution technique was used to determine pHi from the distribution volume of dimethyloxazolidine-2,4-dione (DMO). Perfusion conditions influenced pHi. There was a curvilinear relationship between pHi and flow rate and a linear relationship between pHi and temperature. Under equivalent perfusion conditions there were no significant differences between pHi in normal livers (7.27 +/- 0.02) and that following partial hepatectomy (7.27 +/- 0.03 at 0 h, 7.27 +/- 0.04 at 4 h, 7.28 +/- 0.03 at 8 h, and 7.31 +/- 0.02 at 24 h) or sham surgery (7.27 +/- 0.04 at 4 h, 7.33 +/- 0.08 at 24 h). Therefore intracellular alkalinization does not occur following partial hepatectomy and is unlikely to be a signal for regeneration.

Animals↗

PubMed2004

Hypophosphatemia after right hepatectomy for living donor liver transplantation.

Hypophosphatemia has been described in patients undergoing right hepatectomy for liver cancer and in living donors for liver transplantation who also received total parenteral nutrition. At the study centre, significant hypophosphatemia (0.36 mmol/L or less) requiring intravenous replacement was seen in two of the first nine living donors for adult-to-adult liver transplantation. To determine the frequency of hypophosphatemia in living donors, the authors obtained phosphate levels on stored serum samples from postoperative days 0, 1, 3 and 7 in all nine patients, none of whom were on total parenteral nutrition. Within the first week, hypophosphatemia developed in 55.6% of patients and phosphate levels returned to normal by day 7 in all nine patients. One patient had normal phosphate levels during the first week, but had profound hypophosphatemia (0.32 mmol/L) on day 14 when he presented with a Staphylococcus aureus infection of a bile collection and significant hypoxemia. The extent of hepatectomy and the rate of liver regeneration, estimated by baseline and postoperative day 7 volumetric computed tomography scans, did not correlate with the development of hypophosphatemia. In conclusion, hypophosphatemia is common in living donors undergoing right hepatectomy and may be associated with complications. All living donors should be monitored for the development of hypophosphatemia during the first two postoperative weeks.

Adult↗

PubMedDate not supplied

Accelerated recovery of glycerol-induced acute renal failure in rats with previous partial hepatectomy.

Several studies have reported a favorable effect following the administration of growth factors during the course of acute renal failure. To evaluate the effect of an increased endogenous production of growth factors, rats underwent 70% hepatectomy before glycerol-induced acute renal failure. The renal function was then monitored 12 and 48 h after glycerol injection in conscious rats. Twelve hours after the induction of acute renal failure, a reduction in creatinine clearance and sodium reabsorption was seen in both prehepatectomized and sham-hepatectomized rats. At 48 h, there was total recovery of glomerular filtration and tubular function in the prehepatectomized rats, whereas the sham-hepatectomized rats still had reduced glomerular filtration and sodium reabsorption. In rats treated with dexamethasone before hepatectomy and studied 48 h after the induction of acute renal failure, the protective action on renal function seen in prehepatectomized rats was totally blocked. A semiquantitative histological analysis done 48 h after the induction of acute renal failure demonstrated a fourfold increase in the number of necrotic tubules in both sham-hepatectomized and dexamethasone-treated rats as compared with hepatectomized rats. It is concluded that partial hepatectomy, a maneuver used to increase the endogenous synthesis of growth factors, accelerates recovery of renal function following glycerol-induced acute renal failure.

Absorption↗

PubMedDate not supplied

Serum obtained from rats after partial hepatectomy enhances growth of cultured colon carcinoma cells.

Tumour-bearing rats were randomized to a 70% partial hepatectomy or a sham operation. At days 1, 3 or 14, portal and systemic serum was obtained and colon carcinoma cells were cultured in the presence of 5, 10, 20 or 50% serum. Proliferation and epidermal growth factor receptor (EGFr) expression was measured in tumour cells. Proliferation was 25-40% higher in tumour cells cultured with portal serum after hepatectomy than after sham operation when using serum obtained at day 3, but not days 1 and 14 after operation. In cultures with serum obtained at day 14 after operation CC 531 cells showed a 30% higher proliferation rate with systemic hepatectomy serum than CC 531 cells with sham systemic serum. These effects were not mediated by a change in EGFr mRNA and protein levels as the used colon carcinoma cells did not reveal EGFr activity by any of the three detection methods used.

Adenocarcinoma↗

PubMed2001

Hepatectomy using the coagulating shears type of ultrasonically activated scalpel.

Since the ultrasonically activated scalpel (UAS) incorporates multiple functions, we have used it for hepatectomies. The present study discusses the noteworthy points and problems of use, and shows initial results. Intraoperative ultrasonography is an important tool for comprehending the positional relationship between the plane of division and the main blood vessels. It allows initial adjustment of coagulation and cutting effects according to the rigidity of the liver parenchyma by means of variable ultrasound levels and exchangeable blade tips, and offers good visibility of the cut surface in deep sites as long as adequate tension on the tissue and an upper position for the blade are maintained. 30 patients underwent hepatectomies using the UAS. The amount of blood loss for lobectomy was significantly less than that for partial lobectomy in normal livers in addition to a significant difference between normal and damaged livers in each group according to the extent of resection. There were no serious complications seen in all cases during the operation. The incidence of positive bile leakage was high. It is recommended that bile leakage testing be carried out as thoroughly as possible. There were 3 postoperative bile fistulas and 1 postoperative hemorrhage. In conclusion, although a dramatic improvement in blood loss and shortened operating time could not be obtained in all procedures, the safety and usefulness were demonstrated in lobectomy. The UAS can be considered as a surgical device that can contribute to the efficiency of hepatectomy, depending on the indications selected.

Blood Loss, Surgical↗

PubMedDate not supplied

Total hepatectomy model in pigs: revised method for vascular reconstruction using a rigid vascular prosthesis.

Total hepatectomy in animals provides an irreversible model of acute liver failure. Vascular reconstruction in this model of acute liver failure was modified and characterized for the use of assessment of liver support systems. Pigs underwent total hepatectomy and a rigid three-way transparent polyethylene vascular conduit was used to replace the retrohepatic caval vein and to shunt the portal venous blood to the caval vein. Placement of the vascular conduit in conjunction with excision of the liver was completed in 10-22 min without the need of a temporary veno-venous bypass. A survival study conducted in 5 animals showed a mean survival time of 46 +/- 6 h. Baseline and 4 h postoperative hemoglobin levels were not different, and plasma ammonia levels rose to more than 30-fold of baseline values. All animals died of cardiac arrhythmias and irreversible shock. Total hepatectomy in the pig using a three-way portal-venous conduit is a reliable and well-reproducible animal model of acute liver failure for evaluation of liver assist devices.

Ammonia↗

PubMed2006

In situ graft-trimming method using polyester vascular prosthesis for inferior vena cava reconstruction after hepatectomy.

Hepatectomy for secondary liver cancer that has invaded the inferior vena cava (IVC) can be the only way to achieve long-term survival. We describe a method for hepatectomy combined with partial IVC resection without venous bypass circulation and an in situ graft-trimming method to avoid graft size mismatch after reconstruction. We carried out left hepatectomy extended to segment 1 with partial IVC resection first. During resection and reconstruction of the IVC, it was clamped below the right hepatic vein and above the inferior right hepatic vein to maintain systemic circulation. The graft was trimmed in situ, after a half running suture of the graft was finished to ensure the correct size. Preservation of both inferior right hepatic vein and right hepatic vein helps to maintain systemic circulation during reconstruction of the IVC. The in situ graft-trimming method is an easy and safe method to ensure the correct graft size after IVC reconstruction.

Blood Vessel Prosthesis Implantation↗

PubMed1981

Circulating hepatodepressant factors decreasing the energy charge levels of the remnant liver after hepatectomy.

In 25% hepatectomized rabbits, the mitochondrial phosphorylative activity and the energy charge [(ATP + 1/2 ADP)/(ATP + ADP + AMP)] levels of the remnant liver remained unchanged after hepatectomy. In 70% hepatectomized rabbits, the energy charge levels of the remnant liver decreased maximally 24 h after hepatectomy (p less than 0.001), simultaneously with a marked enhancement of mitochondrial phosphorylative activity (P less than 0.001). Afterward, both returned to normal levels within 4 days. In 93% hepatectomized rabbits, the energy charge levels fell rapidly, with an inhibition of mitochondrial phosphorylative activity, within 6 h after hepatectomy. When a 24-hour 70% hepatectomized rabbit was cross-circulated with a normal rabbit, the energy charge in the liver of the normal partner decreased to 0.732 at 30 min after the blood exchange and then returned to 0.855 while that in the remnant liver of the hepatectomized partner increased from 0.767 to 0.820 (p less than 0.001). Also, the energy charge values of a 24-hour 70% hepatectomized rabbit were increased by the extracorporeal normal liver perfusion. It is suggested that a decrease in the energy charge of the remnant liver is due, at least partly, to the accumulation of the substances consuming hepatic energy (hepatodepressant factors) in the systemic blood of hepatectomized rabbits.

Adenine Nucleotides↗

PubMed1982

A microsurgical method for total hepatectomy in the rat.

A microsurgical three-stage-procedure for total hepatectomy in the rat is described. In the first stage, suprarenal ligature and division of the inferior vena cava is performed. A modified portacaval shunt is constructed in the second stage and total hepatectomy is performed in the third stage. Microsurgical technique is of great benefit in both the second and third stages, especially in choosing the proper location for the shunt and minimizing blood loss. All the rats survived to the 6-hour study and 65% of the rats survived to the 18-hour study, despite the fact that body temperature was upheld to a level of 35-37 degrees C. Based on our experience in 165 hepatectomies, we recommend our method for metabolic studies in anhepatic rats.

Animals↗

PubMed1995

Effect of bile obstruction on liver regeneration following major hepatectomy: an experimental study in the rat.

The regeneration of the liver following resection is regulated by a variety of factors and it might be expected that jaundice influences the process. We therefore evaluated the regenerative response to major hepatectomy in bile-obstructed rats. Two weeks after ligation of the common bile duct, a standardized 77% hepatectomy was undertaken. The jaundiced animals showed an augmented liver regeneration compared to nonjaundiced individuals (p < 0.01). However, blood clearance of radiolabelled Escherichia coli bacteria was impaired (p < 0.01) in animals with bile obstruction at 7 days after the hepatectomy, accompanied by reduced bacterial uptake in the liver as a sign of impaired reticuloendothelial system function.

Animals↗

PubMed1996

Increased serum interleukin-6 level and reduction of hepatic acute-phase response after major hepatectomy.

It has been proposed that a major hepatectomy impairs the liver-related host defense mechanism. The changes in the levels of serum inflammatory cytokines and plasma acute-phase proteins synthesized in the liver were measured after partial hepatectomy. Peak levels of serum interleukin-6 were significantly higher after extended lobectomy than after lobectomy or segmentectomy (p < 0.01). Serum interleukin-1 beta and tumor necrosis factor alpha levels showed no significant changes. Plasma levels of acute-phase proteins were significantly lower after lobectomy or extended lobectomy (p < 0.05). A reduced hepatic acute-phase response probably renders patients liable to infection after major hepatectomy.

Acute-Phase Proteins↗

PubMed1996

Endogenous endotoxemia after massive hepatectomy and portal vein stenosis: beneficial effect of a prostaglandin I2 analogue on intestinal permeability.

Portal vein (PV) stenosis may contribute to operative death after extended hepatectomy combined with PV reconstruction leading to impairment of the intestinal mucosal barrier. This study was designed to investigate whether rats undergoing such surgery developed endogenous endotoxemia and increased intestinal permeability. The effect of a prostaglandin I2 (PGI2) analogue on mucosal barrier function was also studied. The rats were divided into the following five groups: sham operation, massive hepatectomy (Ht), PV stenosis (PS), combined Ht and PS (Ht+PS), and Ht+PS with subcutaneous injection of PGI2 preoperatively (PG). The 10-day survival rate, portal endotoxin level and intestinal permeability (two-sugar test) were evaluated in each group. The Ht+PS group showed a significant increase in both the portal endotoxin level and intestinal permeability (p < 0.05) and a significant worse 10-day survival (p < 0.01) than the other four groups. PGI2 pretreatment did not influence splanchnic blood flow, but decreased the endotoxin level and reduced intestinal permeability. In conclusion, the synergistic effect of massive hepatectomy and PV stenosis induced an increased intestinal permeability and consequently endotoxemia. PGI2 pretreatment significantly improved both intestinal barrier function and survival.

Animals↗

PubMed1991

Changes in prolactin cells caused by partial hepatectomy in the rat.

In order to study ultrastructure alterations in prolactin (PRL)-secreting cells, PRL cells of the anterior pituitary glands of partially hepatectomized female rats were observed by the protein A-gold procedure with the electron microscope. Simultaneously, their serum PRL and estradiol (E2) levels were measured by radioimmunoassay. After about 70% hepatectomy PRL cells were remarkably changed, that is active granule extrusion, prominent Golgi vesicles and a hypertrophic rough endoplasmic reticulum were observed. These changes were most remarkable on day 3 after the operation. Significant increases in serum PRL and E2 were also seen following partial hepatectomy. It may be assumed that the morphological changes in PRL cells and the elevation of serum PRL were probably due to surgical stress and to the diminution of E2 receptors in the liver after partial hepatectomy in the rat.

Animals↗

PubMed1980

Possible significance of changes in the energy metabolism for the release of liver lactate dehydrogenase and for the uptake and incorporation of [14C]-orotic acid into liver ribonucleic acid after partial hepatectomy.

The mouse liver revealed no increased incorporation of [14C]-orotic acid into either the total acid-soluble fraction, the uridine triphosphate or the RNA at 6 and 24 h after partial hepatectomy. In regenerating mouse and rat liver, the concentration of adenosine triphosphate was decreased 15-20% at 6 h, but was in the same range as that of the controls at 24 h. The adenosine monophosphate concentration of mouse liver increased 4-fold and 2-fold at these times after partial hepatectomy, respectively. The results indicate no direct relationship between the energy metabolism and the uptake and incorporation of orotic acid into RNA of regenerating liver. The activity of mouse plasma lactate dehydrogenase 5 (LDH 5) was increased 12-fold at 6 h and 5-fold at 24 h after partial hepatectomy. In rat, the LDH 5 activity was increased 2-fold at 6 h but was not different from that of the controls at 24 h. An increased leakage of LDH 5, possibly related to the decreased energy content of the liver, was thus revealed by the partially hepatectomized mice.

Adenine Nucleotides↗