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Insulin secretion and sensitivity after partial hepatectomy in the rat.

It is known that following partial hepatectomy in the rat hyperinsulinemia evolves, yet glucose intolerance exists. This pattern could be explained by peripheral insulin insensitivity and a compensatory insulin hypersecretion. In the present study, we examined in vivo insulin secretion and sensitivity in partially hepatectomized rats. We found that the increase in plasma insulin levels during i.v. infusion of glucose (10 mg/min) was exaggerated at 1 and 3 days after partial (68%) hepatectomy (P less than 0.001) compared with that in sham-operated controls. In contrast, at days 7 and 14 the plasma insulin response to glucose was not different from that in controls. To study the in vivo insulin sensitivity, a 3-h i.v. infusion of adrenaline, propranolol, glucose, and variable amounts of insulin were given at 3 days after partial hepatectomy. In this model, the ensuing glycemia, being stable during the 3rd hour of infusion, depends on the plasma insulin levels and insulin sensitivity. It was found that the relation between plasma insulin and plasma glucose levels was not different between partially hepatectomized and sham-operated rats. This indicates the same peripheral sensitivity to insulin in these two groups. We conclude that insulin hypersecretion is already evident even at day 1 after partial hepatectomy, whereas after 7 days this hypersecretion has vanished. Furthermore, the study shows that insulin sensitivity is not altered by partial hepatectomy.

Animals↗

Effect of partial hepatectomy on glucose-stimulated insulin release from perfused rat pancreas.

To investigate the functional reserve of the endocrine pancreas both in the early and in the recovering stage after partial hepatectomy, we evaluated the changes in the secretion of insulin in response to a glucose load in isolated perfused rat pancreas 4 and 7 d after about 70% hepatectomy in rats. Insulin responses to a high glucose load (16.7 mM) were significantly higher in the first stimulation phase (first 10 min (p less than 0.01 at 4 and 7 d), and the second stimulation phase (second 20 min) (p less than 0.01 at 4 and 7 d), after hepatectomy. These results indicate that in the regenerating stage after hepatectomy, the sensitivity of islet B-cells to a glucose load is increased to support the increased glucose metabolism in this stage. Thus, this insulin hypersecretion from B-cells seems to be among the adaptations of the endocrine pancreas after hepatectomy.

Animals↗

Hepatectomy simulation discrepancy between radionuclide receptor imaging and CT volumetry: influence of decreased unilateral portal venous flow.

BACKGROUND: Regional dysfunction demonstrated by Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl human serum albumin (GSA) scintigraphy due to regional decrease in the portal venous flow has previously been reported. In this study, we call attention to the significance of unilateral portal venous flow decrease for preoperative hepatectomy simulation, and evaluate the hepatectomy simulation discrepancy between Tc-99m-GSA single-photon emission computed tomography (SPECT) and CT volumetry. METHODS: Twenty-four hepatectomy candidates underwent preoperative hepatectomy simulation by both Tc-99m-GSA SPECT and CT volumetry. Both anatomical and functional resection ratios were calculated by means of CT volumetry and Tc-99m-GSA SPECT, respectively. The differences and ratios between anatomical and functional resection ratios were calculated in all patients, and compared in patients with and without unilateral portal venous flow decrease. RESULTS: Anatomical resection ratios were 28.0 +/- 11.7 (mean +/- standard deviation) in patients with unilateral portal venous flow decrease, and 42.1 +/- 15.7 in patients without unilateral portal venous flow decrease (p = 0.0127). Functional resection ratios were 14.7 +/- 12.8 in patients with unilateral portal venous flow decrease and 40.5 +/- 14.6 in patients without (p = 0.0004). The differences between anatomical and functional resection ratios were 13.0 +/- 7.9 in patients with unilateral portal venous flow decrease and 5.6 +/- 3.1 in patients without (p = 0.0099). The ratios between anatomical and functional resection ratios were 0.48 +/- 0.29 in patients with unilateral portal venous flow decrease and 0.86 +/- 0.10 in patients without (p = 0.0018). In 12 of the 13 patients with unilateral portal venous flow decrease, anatomical resection ratios were found to be larger than functional resection ratios, whereas this happened in only 6 of 11 patients without unilateral portal venous flow decrease (p = 0.0063). CONCLUSION: Unilateral portal venous flow decrease is suspected to be a major factor in the discrepancy between hepatectomy simulations with radionuclide receptor imaging and CT volumetry.

Adult↗

Influence of hepatic regeneration after partial hepatectomy on theophylline pharmacokinetics in rats.

The influence of hepatic regeneration after partial hepatectomy on theophylline pharmacokinetics has been studied on the rat. At different times after partial hepatectomy, theophylline was administered intravenously as a single dose of 6 mg/Kg. Drug plasma levels were determined by HPLC and pharmacokinetic parameters were obtained. Physiological parameters were also measured. Following hepatectomy, an increase in mass liver was observed and 15 days after surgery, liver mass was 78% of nonhepatectomized rats. Initial theophylline concentrations varied during the regeneration period, as well as the distribution volume at steady-estate (Vss). Elimination half-life (t 1/2), notably increased after hepatectomy (7.27+/-1.38 h), decreased with time (6.70+/-1.18 h, 6.47+/-0.69 and 5.17+/-0.87 h after 24 h, 3 days and 15 days post-hepatectomy, respectively) to reach a value close to that of the control group (4.30+/-1.37 h). The increase in elimination half-life led to a decrease in the mean residence time during the period of liver regeneration. However, the intrinsic clearance hardly varied during regeneration period. We could establish the following relationship between liver weight (LW) and the elimination half-life: t 1/2 (h)=-0.358*LW (g)+8.6168 (R2=0.9906). For the mean residence time (MRT) this relationship was: MRT (h) =-0.5173*LW (g)+12.433 (R2=0.991).

Algorithms↗

Relevance of two-stage total hepatectomy and liver transplantation in acute liver failure and severe liver trauma.

Emergency liver transplantation frequently is the only life-saving procedure in cases of acute liver failure. It remains unclear whether emergency hepatectomy with portocaval shunt followed by liver transplantation as a two-stage procedure should be performed in cases in which a donor organ is not yet available. It has been stated that "toxic liver syndrome" could be treated by means of this strategy. From 1990 to 1995 we performed emergency hepatectomies in eight cases of acute liver failure or traumatic liver rupture with exsanguinating bleeding. In six cases we were able to perform a subsequent liver transplantation. Five of the six patients who underwent an emergency hepatectomy died. Emergency hepatectomy led to a significant increase in epinephrine dosage until the transplantation was performed. Only after transplantation did the need for epinephrine therapy decrease. The need for oxygen support did not change during the entire observation period. Plasmatic coagulation was stabilized by substitution, showing significantly higher values at 24 h after transplantation than at 48 h before transplantation. Fibrinogen increased significantly after transplantation in this group of patients. The experiences gathered at our clinic, however, do not show advantages that would allow a recommendation of emergency hepatectomy and subsequent liver transplantation as a two-stage procedure except for situations of severe and uncontrollable hepatic bleeding. Considering the progressive destabilization of our patients, fast procurement of donor organs seems to be of imminent importance for the outcome.

Acute Disease↗

Preoperative evaluation of hepatic vasculature by three-dimensional computed tomography in patients undergoing hepatectomy.

BACKGROUND: Hepatectomy is particularly difficult when the tumor is large, close to the inferior vena cava or the main trunk of the hepatic or portal vein, or in the caudate lobe, as well as when the operation is a re-hepatectomy, because two-dimensional computed tomography (CT) often does not clearly show tumor location relative to blood vessels. STUDY DESIGN: To evaluate the efficacy of three-dimensional computed tomography (3D-CT), reconstructed from multidetector-row computed tomography (MD-CT) with contrast, MD-CT was performed in 17 patients before hepatectomy. RESULTS: The third-order branches of the hepatic artery and the portal vein were clearly shown in all cases. Both the hepatic vein, which drained the same segment that the portal vein fed, and the portal vein were also clearly shown. These vessels could be visualized from any perspective. In 2 patients who underwent hemihepatectomy, large tumors (23.0 and 17.0 cm) displaced the vasculature, but the positions of tumor and vessels could be precisely evaluated by 3D-CT. In patients who required replacement of the vena cava with synthetic grafts, the distance and direction of pressure to IVC by tumor was accurately estimated by 3D-CT. In patients who were limited to segmentectomy or partial hepatectomy because of prior hepatectomy or tumor position, evaluation of the glissons was facilitated by 3D-CT. CONCLUSIONS: Three-dimensional-CT was extremely useful for preoperative simulation because it provided important information that could not be obtained with 2D-CT.

Adolescent↗

Major hepatectomy in children: approaching blood transfusion-free.

INTRODUCTION: Major hepatectomy complicated with massive blood loss requires blood transfusion, which may result in increased morbidity and mortality. Intraoperative techniques and postoperative management that achieves blood transfusion-free major hepatectomy in children are described. METHODS: Fourteen children with a mean age of 3.1 years and mean body weight of 14 kg underwent major hepatectomy between May 1994 and September 2002. Demographic information, surgical techniques, and intraoperative management were analyzed. RESULTS: Hepatectomy included right trisegmentectomy in seven cases, extended right lobectomy in three, right lobectomy in two, and left lobectomy in two. Preoperative imaging, hemihepatic inflow control, intraoperative ultrasonography, and ultrasonic dissection were routinely applied. Fluid was restricted to target a low central venous pressure (5 cm H(2)O) during transection. Postoperative low hemoglobin (>6.3 g/dl) was tolerated in pediatric patients. There was no operative mortality or major complications and only two cases of pleural effusion. The mean blood loss was 68 ml (range 1.25-13.0 ml/kg), and no blood transfusions were required intraoperatively. Blood transfusion was given because of a liberal strategy for major operation in two patients and preoperative tumor bleeding in one. CONCLUSIONS: Despite being technically challenging, major hepatectomy can be performed with minimal blood loss and without blood transfusion in children to decrease postoperative complications.

Blood Loss, Surgical↗

Indication of hepatectomy for cirrhotic patients with hepatocellular carcinoma classified as Child-Pugh class B.

We clarified the indication of partial hepatectomy in hepatocellular carcinoma (HCC) patients with liver cirrhosis classified as Child-Pugh class B. Univariate analysis revealed that adverse prognostic factors were (1) the presence of ascites, (2) elevated total bilirubin (1.5 mg/dl or higher), (3) reduced choline esterase (160 IU/ or lower), (4) elevated alpha-fetoprotein (AFP) (400 ng/ml or higher), (5) microscopic vascular invasion, and (6) non-curative hepatectomy. Microvascular invasion was excluded in the multivariate analysis because this factor could not be predicted before hepatectomy. Multivariate analysis revealed that independent adverse prognostic factors were (1) elevated total bilirubin (1.5 mg/dl or higher), (2) presence of ascites, (3) elevated AFP (400 ng/ml or higher), and (4) non-curative hepatectomy. The overall 5-year survival rate of patients with none of or only one of the four adverse prognostic factors was 45.8%. The overall 5-year survival rate of patients with two or more adverse prognostic factors was only 7.0%. Partial hepatectomy is the first choice of treatment for patients with none of or only one of the four adverse prognostic factors, whereas orthotopic liver transplantation or other conservative treatment should be considered for patients with two or more adverse prognostic factors.

Adult↗

Clinicopathologic features of hepatocellular carcinoma patients with compensated cirrhosis surviving more than 10 years after curative hepatectomy.

BACKGROUND: The aim of this study was to clarify the clinicopathologic features of hepatocellular carcinoma (HCC) patients with compensated cirrhosis surviving more than 10 years after initial hepatectomy. STUDY DESIGN: Among 250 patients who underwent hepatectomy for HCC between 1987 and 1994 at our institute, 145 patients who had Child-Pugh class A liver function and who underwent curative resection were included in this study. Clinicopathologic factors in 10-year survivors and patients who died within 10 years (nonsurvivors) were compared, and the prognostic factors affecting survival were identified. RESULTS: There were 29 patients who survived for more than 10 years after initial hepatectomy, and 9 of those patients survived without cancer recurrence. The 3-, 5-, and 10-year survival rates were 76.2%, 53.0%, and 26.9% respectively. The corresponding disease-free survival rates were 43.1%, 25.7%, and 9.9% respectively. In multivariate analysis, liver fibrosis grade F0-2, female gender, ICG-R15 value of less than 15%, and absence of microscopic vascular invasion were favorable independent factors associated with 10-year survival. Disease-free interval after initial hepatectomy in 10-year survivors with recurrence was significantly longer than that in nonsurvivors with recurrence, 5.1 and 1.9 years respectively (P = 0.0004). The number of intrahepatic recurrent nodules in 10-year survivors tended to be fewer than that in nonsurvivors. CONCLUSIONS: Based on the results of our study, liver fibrosis grade F0-2, female gender, ICG-R15 value of less than 15% and absence of microscopic vascular invasion at initial hepatectomy might be biologically favorable conditions for long-term survival. Close follow-up as well as multimodal treatment could contribute to prolongation of survival in such patients, even if HCC recurrence develops.

Adult↗

Carnitine contents in remnant liver, kidney, and skeletal muscle after partial hepatectomy in rats: randomized trial.

Carnitine, an important carrier of free fatty acid that is transported into mitochondria for beta-oxidation, was thought to be one of the key factors in the regulation of liver regeneration. If the carnitine content is insufficient in the hepatocyte, it might impair the energy substrate's transport and the energy charge required for cell regeneration. The purpose of this study is to evaluate the changes of carnitine content in remnant liver, kidney, and skeletal muscle simultaneously after partial hepatectomy in rats. Partial hepatectomy with resection of the median and left lateral lobes was performed on male Wistar rats. Rats with a sham operation comprised a control group. This study was an experimental randomized trial. Ten rats from each group were sacrificed before the operation and at 6, 24, 48, and 72 hours after the operation. The carnitine content, as total and free forms, in remnant liver, kidney, and skeletal muscle were quantified by high-performance liquid chromatography. The carnitine contents in the remnant liver increased significantly at 6, 24, and 48 hours after partial hepatectomy (p < 0.01). The increase of total carnitine content was more obvious than that of the free form. In contrast, the decreasing concentrations of total carnitine and free carnitine in the kidney were significant (p < 0.01). In skeletal muscle the total carnitine content decreased to a small extent, and it was observed only at 6 hours after partial hepatectomy (p < 0.05). It is suggested that remnant liver promoted the generation of carnitine, whereas kidney and skeletal muscle released their stored carnitine at an early stage after partial hepatectomy. As a result, the influx of the carnitine into hepatocytes increased at the regenerative stage. The carnitine content of remnant liver is sufficient during the early posthepatectomy stage.

Animals↗

Is parenchyma-preserving hepatectomy a noble option in the surgical treatment for high-risk patients with hilar bile duct cancer?

BACKGROUND: The essential minimum of hepatic segmentectomy combined with caudate lobectomy (parenchyma-preserving hepatectomy) has been recommended particularly for high-risk patients with hilar bile duct cancer to minimize the risk of postoperative liver failure. This quality control study investigated whether parenchyma-preserving hepatectomy is a "noble option" in the surgical treatment of hilar bile duct cancer. PATIENTS AND METHODS: A total of 53 patients with hilar bile duct cancer underwent surgical resection. These patients were retrospectively classified into a major hepatectomy group (major Hx, n=30), a parenchyma-preserving hepatectomy group (preserving Hx, n=11), and a hilar bile duct resection group (HBDR, n=12). A preserving Hx consisted of caudate lobectomy, either alone (n=3), or combined with resection of segment 4 (S4, n=4), or S58 (n=3) or S458 (n=1). The preserving Hx was used for high-risk patients in whom tumor tissue was diagnosed to be Bismuth type I and II by preoperative selective percutaneous transhepatic cholangiography. RESULTS: The mean numbers of hepatico-jejunostomies were 2.8, 4.8, and 4.6 in the respective groups. Mortality rates including hospital death were 13.3%, 0%, and 0% respectively. Morbidity rates were 46.7%, 54.5%, and 33.3%. The preserving Hx group encountered no liver failure (T.Bil>10 mg/dl, encephalopathy) but acquired hyperbilirubinemia (T.Bil>5 mg/dl), pulmonary insufficiency and other complications at the same frequency as in the major Hx group. The survival rates in the three groups were 35.6%, 52.5%, and 48.6% at 3 years and 25.2%, 14.9%, and 24.3% at 5 years respectively. Curability rates (R0 to R1+2) were 76.7%, 54.5% and 50.0%, respectively. Preserving Hx tended to result in higher frequencies of positive transmural margins (e.g., cancer cells remaining around the right hepatic artery or the portal vein). CONCLUSIONS: Preserving hepatectomy for high-risk patients should be limited strictly to patients who do not have tumors which are not invading adjacent organs (e.g., T2) nor a segmental duct and are confined longitudinally to the right or the left.

Adenocarcinoma↗

Pre-hepatectomy prognostic staging to determine treatment strategy for colorectal cancer metastases to the liver.

BACKGROUND: Attempts at identifying prognostic factors after hepatectomy in patients with colorectal liver metastases have not achieved consensus. We investigated prognostic factors ascertainable before hepatectomy for colorectal metastasis. METHOD: Clinicopathological data for 149 consecutive patients with colorectal cancer who underwent curative resection of primary lesions and metastatic liver disease at one institution were subjected to multivariate analysis concerning metastatic status and the primary lesion. RESULTS: Poorly differentiated adenocarcinoma or mucinous carcinoma as the primary tumor (Poor/muc; P=0.026), marked vascular invasion by the primary tumor (V; P=0.002), bi-lobar liver metastases ( P=0.048), and short doubling time (DT) of the liver tumor ( P=0.028) were characteristics assessable before hepatectomy that independently indicated poorer survival. A four-stage classification based on these factors was related to overall ( P<0.01) and disease-free ( P<0.01) survival rates. No pattern of recurrence site was evident in stage I (patients with no risk factor). Recurrence was usually extrahepatic in stage IV (patients with Poor/muc) but favored the remnant liver in stage II (patients with bi-lobar metastases or short DT) or III (patients with V; P=0.037). Stage III showed more multiple and early hepatic recurrences than stage II, and repeat hepatectomy was less frequent ( P<0.05). CONCLUSION: Pre-hepatectomy prognostic staging should help to guide treatment of liver metastases.

Colorectal Neoplasms↗

Liver regeneration after partial hepatectomy is non-uniform: flow cytometric bromodeoxyuridine incorporation and cell cycle studies in a porcine model.

The rate of hepatocyte regeneration at different anatomical locations of the remnant liver after partial hepatectomy was assessed in porcine hepatocytes by bromodeoxyuridine (BrdUr) incorporation and cell cycle kinetics using flow cytometric analysis. Partial hepatectomy was performed in five Yorkshire pigs. A single intravenous injection of BrdUr at 50 mg/kg was administered on the 2nd post-operative day and the animals were sacrificed 1 h later. The remnant liver tissue was harvested and divided into four equal zones, from the liver periphery towards the surgical cut-edge. Biopsy samples were obtained from the centre of each of these zones and similarly from identical anatomical locations in two control pigs that had undergone sham surgery. Hepatocyte nucleus suspension was prepared, double labelled with anti-BrdUr and propidium iodide and analysed by a flow cytometer. The cells in S-phase was used as the parameter to measure the regeneration status. A gradient increase in S-phase from the periphery to the cut edge was observed in all five pigs that had undergone partial hepatectomy. The percentage of S-phase cells in all four zones from the hepatectomy group was significantly higher when compared with that in the controls. Liver regeneration after partial hepatectomy was not uniform but was greatest adjacent to the surgical cut edge and decreased towards the periphery of the liver.

Animals↗

Laparoscopic hepatectomy with the hook blade of ultrasonic coagulating shears and bipolar cautery with a saline irrigation system.

BACKGROUND: The number of patients who have undergone laparoscopic hepatectomy is small, and the operative procedure is not yet well established. METHODS: We performed laparoscopic hepatectomy in eight patients, using the hook blade of ultrasonic coagulating shears, and bipolar cautery with a saline irrigation system, with minilaparotomy. The operative time, blood loss, and postoperative hospital stay of patients with laparoscopic left lateral segmentectomy were compared with these parameters in ten patients who had had a left lateral segmentectomy with laparotomy. RESULTS: The laparoscopic hepatectomies included seven left lateral segmentectomies and one nonanatomical partial resection of the lateral segment. The mean duration of the operation in these eight patients was 181.1 +/- 44.6 min. The mean amount of blood loss was 177.6 +/- 129.1 ml. Postoperative complications consisted of two cases of bleeding. The mean postoperative hospital stay in all eight patients was 9.88 +/- 4.36 days. The mean duration of operation (185.9 +/- 46.0 min) and mean postoperative hospital stay (9.47 +/- 4.61 days) in the seven patients with laparoscopic left lateral segmentectomies were significantly shorter than these parameters (255.7 +/- 59.4 min and 24.6 +/- 8.82 days) in the ten patients who had had left lateral segmentectomies with laparotomy. The mean amount of blood loss (160.0 +/- 128.9 ml) in the laparoscopic series was less than that (318.5 +/- 192.2 days) in the patients who had had laparotomy. CONCLUSIONS: Laparoscopic hepatectomy with the ultrasonic coagulating shears and bipolar cautery with minilaparotomy was safe, and less invasive than the open procedure, for minor hepatectomy procedures such as left lateral segmentectomy.

Aged↗

The impact of 3-D virtual hepatectomy simulation in living-donor liver transplantation.

BACKGROUND/PURPOSE: In living-donor liver transplantation, accurate assessments of liver graft volume and anatomical variation are mandatory for the preoperative planning of safe donor hepatectomy and successful recipient implantation. The aim of this study was to assess the feasibility and accuracy of novel three-dimensional (3-D) virtual hepatectomy simulation software in living-donor liver transplantation. METHODS: We developed the hepatectomy simulation software, which was programmed to analyze detailed 3-D vascular structure and to predict liver graft volume, based on hepatic circulation. RESULTS: In 101 individuals, including 4 living donors, the predicted liver resection volumes revealed a significant correlation with the actual value (P < 0.0001), with a mean difference of 7.9 ml. The drainage area by the individual hepatic vein branch was quantified to achieve reconstruction of the corresponding venous branch. The application of multidetector computed technology scanning and virtual cholangioscopy facilitated more detailed visualization of the 3-D hilar anatomy in a left trisectoral graft transplantation. CONCLUSIONS: This hepatectomy simulation software reliably predicted accurate liver graft volume and the drainage volume of hepatic vein branches. This software may contribute to the preoperative planning of safe donor hepatectomy and implantation with satisfactory graft viability.

Female↗

Repeat hepatectomy for colorectal metastases.

The utility of repeat hepatectomy for patients with colorectal metastases to the liver was sought. A complete review of the results of surgical treatment of patients having a repeat hepatectomy was presented. Then, the data on 170 patients in whom multiple clinical variables had been tabulated were selected for special study. These statistical analyses showed that there were no special clinical features present at the time of primary resection of the large bowel cancer that could distinguish these patients. There were some differences in the clinical features of these patients at the time of first and second liver resections. The disease-free interval, method of diagnosis, presence of extrahepatic disease, incidence of complete resection, and postoperative morbidity showed significant differences. The 5-year survival of the group as a whole was 32%. Only those clinical features which involved the completeness of cancer resection had a significant impact on survival. To optimize selection for a long-term survival, no extrahepatic disease should be present and the second hepatectomy should involve removal of all visible tumor. Repeat hepatectomy for colorectal metastases was thought to be justified if the patient was made clinically disease-free, because surgery remains the only potentially curative treatment. The repeat hepatectomy was relatively safe with a low morbidity and conferred a 32% long-term survival.

Adenocarcinoma↗

Expression of hepatocyte growth factor mRNA in regenerating rat liver after partial hepatectomy.

Hepatocyte Growth Factor (HGF) is a potent complete mitogen for primary cultures of hepatocytes in vitro. There is strong evidence that this novel growth factor may mediate hepatocyte regeneration after liver damage. We have shown previously that the amount of immunoreactive HGF markedly increases in the serum of rats soon after partial hepatectomy or CCl4 administration. In the present paper, we demonstrate that the level of HGF mRNA in rat liver also dramatically increases from 3 to 6 hours post hepatectomy, peaks at 12 hr and gradually returns to undetectable levels by 72 to 96 hours post hepatectomy. In separate experiments, DNA synthesis (in vivo) was determined in rat liver remnants after partial hepatectomy. DNA synthesis peaked 24 hr after hepatectomy, 12 hr after the peak of HGF mRNA expression. These results suggest that HGF may be one of the major early signals that triggers hepatocyte proliferation during liver regeneration.

Animals↗

The effect of GABA on serum and hepatic polyamine concentrations after partial hepatectomy in rats.

Serum and hepatic polyamine concentrations including putrescine, spermidine and spermine were documented at various time intervals after partial hepatectomy in rats treated with GABA (500 micrograms/gm body wt) or isotonic saline. Aside from a transient decrease in spermidine levels, GABA treatment had no effect on serum polyamine concentrations. In the liver, however, GABA treatment markedly attenuated the increase in hepatic putrescine concentrations that occurs after partial hepatectomy such that levels were 64%, 74% and 100% lower than in saline-treated controls on days 1, 2 and 3 after partial hepatectomy (p less than 0.005, p less than 0.01 and p less than 0.05, respectively). Spermidine and spermine concentrations in the liver were not affected by GABA treatment. To determine the mechanism whereby GABA lowers putrescine concentrations in regenerating liver, ornithine decarboxylase messenger RNA and enzyme activity were documented after GABA treatment. Although ornithine decarboxylase messenger RNA levels were similar, ornithine decarboxylase enzyme activity was significantly inhibited 12 hr after partial hepatectomy in GABA-treated rats compared with saline-treated controls. The results of this study indicate that GABA inhibits hepatic putrescine synthesis at a posttranscriptional level in rats after partial hepatectomy. These results could help to explain the impairment in hepatic regenerative activity that occurs in patients with elevated serum GABA concentrations and fulminant hepatic failure.

Animals↗