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Effect of hepatectomy on the reticuloendothelial system of septic rats.

The purpose of this study was to evaluate the function of the reticuloendothelial system (RES) of sham hepatectomy and 20% and 50% partial hepatectomy (PH 20%, PH 50%), with or without cecal ligation and puncture-induced sepsis. The animals were injected with 51Chromium sheep red blood cells (SRBC) at 72 hours. SRBC half life (T1/2) was measured as an index of RES function and the percentage distribution of SRBC in liver, lung, and spleen was calculated. T1/2 was significantly prolonged in PH 50% rats and was associated with decreased radioactive uptake by the liver. Mortality was nil in the control groups and markedly increased in the presence of sepsis. The results suggest that decreased RES function following hepatectomy is dependent upon the proportion of liver removed and that sepsis further increased the mortality of hepatectomized animals.

Animals↗

Augmentation of cell-mediated cytotoxicity following 50% partial hepatectomy.

The cytolytic responses of C3H/HeJ mice after 50% hepatectomy (PH) were assessed in a 4-hr 51Cr-release assay. Spleen cells (SC) (50 x 10(6] from normal or PH C3H/HeJ (H-2k) mice were sensitized with equal numbers of irradiated allogeneic DBA/2 (H-2d) spleen cells in a five-day mixed lymphocyte culture. Generated cytolytic activity was measured against 51Cr-labeled P815 mastocytoma (H-2d) and EL4 lymphoma (H-2b) target cells. The wet weight and cell numbers per spleen following 50% partial hepatectomy were 70% and 75% higher than the control values for the first 20 days, and then returned to normal levels by 21 days. The cytolysis by spleen cells from 2-, 14-, and 31-day PH mice were 89.3 +/- 0.7, 86.9 +/- 5.3, and 90.1 +/- 1.3%, respectively, compared with control (sham-operated) values of 56.0 +/- 1.0, 57.0 +/- 2.0, and 49.9 +/- 7.0% (P less than 0.03 at E/T 100:1). This enhanced cytolysis by PH spleen cells remained high for at least 118 days after the liver resection before returning to control levels by 268 days. Cytolytic effector cells in PH SC were generated at least 24 hr earlier than in control SC. When normal and PH cytolysis were compared following primary and secondary in vitro sensitization, the cytolytic levels of primarily-sensitized PH spleen cells were comparable to secondarily sensitized normal spleen cells. Furthermore, the primarily sensitized normal spleen cells did not show crossreactive cytolysis with EL4 target cells (H-2b), while both the primarily sensitized PH spleen cells and the secondarily sensitized normal spleen cells were significantly cross-reactive against the third party EL4 target cells. Adherent PH spleen cells appear to be responsible for this augmented cytolytic capacity since their coculture with normal nonadherent responder spleen cells increased control cytolysis by approximately 30%. These studied demonstrate that, following 50% partial hepatectomy, there is an immediate and sustained increase in the allospecific cytolytic response.

Animals↗

Continuous venovenous hemofiltration with dialysis in combination with total hepatectomy and portocaval shunting. Bridge to liver transplantation.

Children who experience acute liver failure following liver transplantation will have multiple organ failure and a high rate of mortality unless emergency retransplantation can be performed. Transplant hepatectomy with portocaval shunting has been described as a bridge to transplantation in the most severe cases, as well as in patients with fulminant hepatic failure at high risk for mortality who have not undergone liver transplantation. Patients with multiple organ failure who have undergone hepatectomy require renal replacement therapy. Continuous hemofiltration may be used in patients with fulminant hepatic failure to facilitate fluid removal and circulatory and metabolic balance. We used continuous venovenous hemofiltration with dialysis following hepatectomy with portocaval shunting in a patient who remained anhepatic for 66 hr in order to achieve circulatory and metabolic homeostasis as well as stable neurologic function prior to successful retransplantation.

Child, Preschool↗

Analysis of postoperative liver function of donors in living-related liver transplantation: comparison of the type of donor hepatectomy.

BACKGROUND: There is a potentially significant risk to the donor in living-related liver transplantation. METHODS: We analyzed surgical risk and stress to 35 donors in living-related liver transplantation with special reference to the types of donor hepatectomy. Donor surgery was performed in one of three ways: (1) lateral segmentectomy without ligation of the middle hepatic vein (MHV) in the remnant liver (group 1, n=21); (2) lateral segmentectomy with ligation of MHV in the remnant liver (group 2, n=6); and (3) left lobectomy with MHV (group 3, n=8). RESULTS: No critical complications were observed in any group. The postoperative enzyme levels in group 2 were significantly higher than those in groups 1 and 3 (P<0.01). Although blood loss was covered by autologous blood transfusion in the first six cases, no banked blood was transfused in any of the cases. Surgical duration was significantly longer and blood loss was significantly greater in group 3 than in group 1 (P<0.05). Follow-up computed tomography showed atrophic changes in segment IV in groups 1 and 2. No remarkable changes were seen in segments V or VIII in any of the three groups. CONCLUSION: Regardless of the donor hepatectomy procedure, serious complications did nor occur after surgery. Although it should be noted that the type of donor hepatectomy affects postoperative donor liver function, left lateral segmentectomy with ligation of MHV in the remnant liver is a useful method for obtaining liver grafts from living-related donors who have unusual anatomic variations of the hepatic veins.

Adult↗

Perturbed bioelectrical properties of the mouse cecum following hepatectomy and starvation: the role of bacterial adherence.

Previous work in our laboratory has demonstrated that bacterial adherence alone to the intestinal epithelium, as occurs following catabolic stress, significantly perturbs the normal electrophysiology of the cecal mucosa. The aim of this study was to further characterize these effects in the mouse cecum following hepatectomy and short-term starvation, and to define the role of bacterial adherence in this process. Groups of mice underwent a surgical hepatectomy and were either fed or starved during the postoperative period. Groups of controls underwent sham operations and were either fed or starved postoperatively. Electrophysiologic studies in Ussing chambers at 48 hours were performed. Bacterial adherence to the mucosa was assessed by culture and histologic staining. To determine the role of bacteria in the altered electrophysiologic response, ciprofloxacin decontamination studies were performed. Only mice subjected to both hepatectomy and starvation developed bacterial adherence of sufficient magnitude (>10(5) cfu/gm) to alter mucosal electrophysiology (short-circuit current and basal potential difference). Ciprofloxacin decontamination completely abrogated this effect. Ion replacement studies suggested that active sodium transport was primarily responsible for the observed changes in mucosal electrophysiology. Bacterial-epithelial cell interactions may be responsible for altered mucosal ion transport observed following operative catabolic stress and short-term starvation.

Animals↗

Endothelial-directed hepatic regeneration after partial hepatectomy.

OBJECTIVE: To determine the role of the microvascular endothelium in the regulation of regenerating liver mass after partial hepatectomy. SUMMARY BACKGROUND DATA: Angiogenesis is critical for both pathologic and physiologic processes. The ability of certain tissues, such as the liver, kidney, and spleen, to regenerate after injury is poorly understood. The liver will regenerate to its normal mass within 8 days of surgical excision. Because the authors have previously shown that the endothelial cell regulates tumor mass, we hypothesized that normal adult organ mass is also controlled by the endothelial cell. METHODS: Two-thirds partial hepatectomy was performed in 7- to 8-week-old C57 BL/6 mice, followed by systemic treatment with either the angiogenesis stimulator basic fibroblast growth factor (bFGF) (1 microg/g/d intraperitoneal) or the angiogenesis inhibitor TNP-470 (30 mg/kg/qod subcutaneous). Groups of three mice were then euthanized on postoperative days 2, 4, 6, and 8, and the livers were weighed and analyzed by immunohistochemistry. RESULTS: bFGF accelerated hepatic regeneration by 42%, 19%, 16%, and 16% on postoperative days 2, 4, 6, and 8, respectively. TNP-470 inhibited hepatic regeneration by 46%, 74%, 67%, and 64% on postoperative days 2, 4, 6, and 8, respectively. Immunohistochemistry revealed that bFGF and TNP-470 primarily affected the endothelial compartment. Specifically, bFGF increased endothelial proliferation and decreased endothelial apoptosis. TNP-470, in contrast, inhibited endothelial cell proliferation. The cessation of the regenerative process correlated with a decrease in endothelial proliferation and an increase in endothelial apoptosis. CONCLUSIONS: The systemic administration of angiogenesis agents modulates the regeneration of hepatic mass primarily by affecting endothelial cell proliferation or apoptosis. Endothelial cell apoptosis is associated with the cessation of the regenerative process in control mice. These results suggest that the endothelial cell is one of the key mediators of regenerating adult tissue mass in this partial hepatectomy model.

Animals↗

Hepatectomy with portal vein resection for hilar cholangiocarcinoma: audit of 52 consecutive cases.

OBJECTIVE: To better determine the role of portal vein resection and its effect on survival, as well as to appreciate the impact of portal vein invasion on prognosis in hilar cholangiocarcinoma. SUMMARY BACKGROUND DATA: Hepatectomy with portal vein resection is sometimes performed for locally advanced hilar cholangiocarcinoma. However, the significance of microscopic invasion of the portal vein has not been determined. METHODS: Medical records of 160 patients with hilar cholangiocarcinoma who underwent macroscopically curative hepatectomy with (n = 52) or without portal vein resection (n = 108) were reviewed. Invasion of the portal vein was assessed histologically on the surgical specimen, and results were correlated with clinicopathologic features and survival. RESULTS: Surgical mortality, including all hospital deaths, was similar in patients who did and did not undergo portal vein resection (9.6% vs. 9.3%), but the primary tumor was more advanced in patients who underwent portal vein resection. Histologically, no invasion was found in 16 (30.8%) of resected portal veins. However, dense fibrosis adjacent to the portal vein was common, and the mean distance between the leading edge of cancer cells and the adventitia of the portal vein was 437 +/- 431 mum. The prognosis was worse in patients with than without portal vein resection (5-year survival, 9.9% vs. 36.8%; P < 0.0001). The presence or absence of microscopic invasion of the resected portal vein did not influence survival (16.6 months in patients with microscopic invasion vs. 19.4 months in those without; P = 0.1506). Multivariate analysis identified histologic differentiation, lymph node metastasis, and macroscopic portal vein invasion as independent prognostic factors. CONCLUSIONS: Microscopic invasion of the portal vein may be misdiagnosed clinically in patients with hilar cholangiocarcinoma. However, the distance between tumor and adventitia is so narrow that curative resection without portal vein resection is unlikely to be possible. Gross portal vein invasion has a negative impact on survival, and hepatectomy with portal vein resection can offer long-term survival in some patients with advanced hilar cholangiocarcinoma.

Adult↗

The "50-50 criteria" on postoperative day 5: an accurate predictor of liver failure and death after hepatectomy.

OBJECTIVE: To standardize the definition of postoperative liver failure (PLF) for prediction of early mortality after hepatectomy. SUMMARY BACKGROUND DATA: The definition of PLF is not standardized, making the comparison of innovations in surgical techniques and the timely use of specific therapeutic interventions complex. METHODS: Between 1998 and 2002, 775 elective liver resections, including 69% for malignancies and 60% major resections, were included in a prospective database. The nontumorous liver was abnormal in 43% with steatosis >30% in 14%, noncirrhotic fibrosis in 43%, and cirrhosis in 12%. The impact of prothrombin time (PT) <50% and serum bilirubin (SB) >50 micromol/L on postoperative days (POD) 1, 3, 5, and 7 was analyzed. RESULTS: The lowest PT level was observed on postoperative day (POD) 1, while the peak of SB was observed on POD 3. These 2 variables tended to return to preoperative values by POD 5. The median interval between hepatectomy and postoperative death was 15 days (range, 5-39 days). Postoperative mortality significantly increased in patients with PT <50% and SB >50 microml/L. The conjunction of PT <50% and SB >50 micromol/L on POD 5 was a strong predictive factor of mortality. In patients with significant morbidity, this "50-50 criteria" was met 3 to 8 days before clinical evidence of complications. CONCLUSIONS: The association of PT <50% and SB >50 microml/L on POD 5 (the 50-50 criteria) was a simple, early, and accurate predictor of more than 50% mortality rate after hepatectomy. This criteria could be identified early enough, before clinical evidence of complications, for specific interventions to be applied in due time.

Chi-Square Distribution↗

Two hundred liver hanging maneuvers for major hepatectomy: a single-center experience.

OBJECTIVE: To establish the indications of the liver hanging maneuver for major hepatectomy. SUMMARY BACKGROUND DATA: The liver hanging maneuver, which is a technique of passing a tape along the retrohepatic avascular space and suspending the liver during parenchymal transection, facilitates anterior approach of major hepatectomy. However, the feasibility and limits of this maneuver have never been established in patients with different clinical backgrounds. METHODS: Medical records of 242 consecutive patients considered for major hepatectomy using the hanging maneuver were reviewed. RESULTS: Among 242 patients, 14 patients (6%) were considered to have contraindication for this maneuver preoperatively because of tumor infiltration to anterior surface of retrohepatic inferior vena cava (IVC). It was successful in 201 patients with overall feasibility of 88%. The feasibility increased significantly in the recent years as compared with the initial years (94% in 2003-2005 vs. 76% in 2000-2002, P < 0.0001). Bleeding during the retrohepatic dissection occurred in 5 patients (2%), which was minor due to injury of hepatic capsule in 3 (1%) and major due to injury of short hepatic vein in 2 (1%). In all cases, bleeding stopped spontaneously. The maneuver was abandoned in 27 patients, including 15 related to severe adhesion between liver and IVC. Univariate analysis showed that adhesion between IVC and liver was the only significant negative predictor affecting the feasibility. Cirrhosis, large tumor, preoperative radiologic treatments did not influence on the feasibility. CONCLUSIONS: The liver hanging maneuver has 94% feasibility in recent years. Absolute contraindication is tumor infiltration to the retrohepatic avascular space. Adhesion between the IVC and liver has a negative impact of the feasibility. According to this indication, the hanging maneuver is easily achievable without risk of the major bleeding during the retrohepatic dissection.

Adolescent↗

Partial hepatectomy with wide versus narrow resection margin for solitary hepatocellular carcinoma: a prospective randomized trial.

OBJECTIVE: To compare the efficacy and safety of partial hepatectomy aiming grossly at a narrow (1 cm) and a wide (2 cm) resection margin in patients with macroscopically solitary hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: For HCC treated with partial hepatectomy, the extent of the margin of liver resection remains controversial despite extensive studies. METHODS: We conducted a prospective randomized trial in patients with solitary HCC. From January 1999 to February 2003, 169 patients with solitary HCC were stratified according to tumor size and randomized to undergo partial hepatectomy aiming grossly at either a narrow (1 cm) (n = 84) or a wide resection margin (2 cm) (n = 85). Analyses were done on an intention-to-treat basis. RESULTS: The demographic and pathologic data were similar in the 2 groups. The mean +/- SD for the final resection margin of the narrow and the wide margin groups were 0.7 +/- 0.4 cm and 1.9 +/- 0.6 cm, respectively. There was no significant difference in the morbidity and in-hospital mortality between the 2 groups of patients. The 1-, 2-, 3-, and 5-year overall survival rates for the narrow and the wide margin groups were 92.9%, 83.3%, 70.9%, and 49.1% and 96.5%, 91.8%, 86.9%, and 74.9%, respectively. The difference was significant (stratified log-rank test, P = 0.008). Multivariate analysis identified the presence of micrometastases and the treatment allocation were independent risk factors for tumor-related death. At the time of censor, 75 (44.4%) patients had developed tumor recurrence. All recurrences at the margins of liver resection were observed in the narrow margin group. Multiple tumor recurrence was also significantly higher in the narrow margin group (chi test, P = 0.018). Survival after tumor recurrence was significantly better in the wide margin group than the narrow margin group (log-rank test, P = 0.017). CONCLUSION: For macroscopically solitary HCC, a resection margin aiming grossly at 2 cm efficaciously and safely decreased postoperative recurrence rate and improved survival outcomes when compared with a gross resection margin aiming at 1 cm, especially for HCC < or =2 cm.

Adolescent↗

Right living donor hepatectomy in the presence of celiac artery stenosis.

BACKGROUND: Incidental celiac artery stenosis has been cited as an exclusion criterion for adult donor right hepatectomy. METHODS: We report our experience involving right donor hepatectomy performed in the presence of isolated high-grade (greater than 80%) celiac trunk stenosis in two young healthy and asymptomatic adult living liver donors. RESULTS: The immediate postoperative course was complicated by a superficial wound infection in one patient and a transient median nerve palsy caused by intraoperative positioning, which spontaneously resolved, in the second patient. Both were discharged within 7 to 10 days postoperatively. They are doing well at 1 year follow-up without any complaints and have both returned to 100% full employment. CONCLUSIONS: Our results show that right donor hepatectomy can be safely performed in the presence of significant celiac artery stenosis. However, careful long-term follow-up will be required to monitor for any future progression of mesenteric vascular disease.

Adult↗

Respiratory complications: a major concern after right hepatectomy in living liver donors.

BACKGROUND: One of the main concerns after living donor liver transplantation is the risk of morbidity and/or mortality that it imposes on the donors. Respiratory postoperative complications in living liver donors have already been reported but their frequency seems to be underestimated. We designed a prospective study to evaluate the rate and the nature of postoperative pulmonary complications in 112 consecutive donors. METHODS: The medical records of the 112 living liver donors operated on at our center from 1998 to 2003 were reviewed and all the cases of respiratory complications were retrieved. Moreover, since 2000, all patients had a computed tomography angiography of the thorax at day 7 on a prospective basis. RESULTS: In all, 112 hepatectomies (44 right and 68 left) for adult-to-adult or adult-to-child liver donation were performed in our center. No postoperative mortality was recorded. Fourteen major respiratory complications developed in of 11 of 112 donors (9.8%), in all cases after right hepatectomy, and included nonsevere pulmonary embolism (n=7), right pleural empyema (n=3), and bacterial pneumonia (n=3). Minor respiratory complications (7.1% of the donors) included iatrogenic pneumothorax (n=3) and pleural effusion requiring thoracocentesis (n=5). Abdominal complications (mainly biliary leak) developed in 10 donors (8.9%), who in the vast majority remained free of pulmonary complications. CONCLUSIONS: In our series, pulmonary complications are frequent in living liver donors. These complications are mainly observed after right hepatectomy. The particular prevalence of pulmonary embolism should lead to focus on its early diagnosis and prevention.

Adolescent↗

The effect of a tumour necrosis factor antibody on the regenerative response after partial hepatectomy in rats.

In this study we investigated the effect of tumour necrosis factor (TNF) on the regenerative response after partial hepatectomy. Adult male rats were injected intravenously with an antibody to TNF immediately after partial hepatectomy. Animals were sacrificed at 0, 24, 48, 72 and 96 h postoperatively. Hepatic thymidine kinase (TK) activity, liver weight to body weight (LW/BW) ratio, and mitotic index (MI) were used as indices of hepatic regeneration. The rats treated with TNF-Ab had significantly lower levels of TK activity in the liver at 24 h postoperatively compared to the saline treated animals. Furthermore the peak hepatic TK activity was delayed to 48 h in the rats treated with TNF-Ab. The mitotic indices and LW/BW ratios in the TNF-Ab- and saline-treated animals were similar. These data suggest that TNF potentiates the regenerative response after partial hepatectomy.

Animals↗

Safety of donor right hepatectomy for adult-to-adult living donor liver transplantation.

The purpose of this study was to ascertain the usefulness of preoperative evaluations of donors by computed tomography (CT) volumetry and CT cholangiography for prevention of unexpected liver failure and biliary complications after donor right hepatectomy for adult-to-adult living donor liver transplantation. Fifty-two donors who underwent right hepatectomy without the middle hepatic vein were enrolled in this study. The values of graft weight (GW) were significantly correlated with those of estimated graft volume (GV; P < 0.0001). GW was predicted by the following formula: GW = 155.25 + 0.658 x GV; r(2) = 0.489. CT cholangiography revealed anatomical variants of biliary structure in one-third of the donors and also clearly showed one or two small biliary branches from the caudate lobe to the right hepatic ducts or the confluence in 58% of the donors. Biliary leakage, which was treated by conservative therapy, occurred in only one donor (1.9%). No donors received homologous blood transfusion. Hyperbilirubinemia (serum total bilirubin >5 mg/dl) occurred in 5.8% of the donors during their early postoperative periods. Precise evaluations of liver remnant volume by CT volumetry and biliary variation by CT cholangiography are essential for performing safe donor hepatectomy, preventing hepatic insufficiency and minimizing the risk of biliary tract complications.

Adolescent↗

Efficacy of hypothermic perfusion using University of Wisconsin solution in extended hepatectomy with hepatic inflow occlusion in a canine model.

This study was designed to elucidate the efficacy of University of Wisconsin (UW) solution for preventing liver injury, when used as a hypothermic perfusate infused into the systemic circulation during extended hepatectomy with hepatic inflow occlusion. Adult mongrel dogs (9.5-17.5 kg, n = 14) were subjected to 75% hepatectomy under 60 min hepatic inflow occlusion. The animals were divided into two groups. The UW group (n = 7) underwent hypothermic perfusion using 4 degrees C UW solution (core temperature of the liver: 12.3 +/- 0.2 degrees C). The control group designated as the Ringer's lactate (LR) group (n = 7) underwent hypothermic perfusion using 4 degrees C LR solution. The perfusate was introduced into the systemic circulation via the hepatic vein. Blood from the hepatic vein was sampled, and alanine aminotransferase, purine nucleoside phosphorylase activities and the ammonia concentration were measured. The 7 day survival rate was higher in the UW group than in the LR group. The parameters of liver function were less significantly altered in the UW group than in the LR group. The plasma ammonia concentration was significantly (P < 0.05) lower 6 h after reperfusion in the UW group than in the LR group. A small volume of hypothermic perfusion of the liver using UW solution was safe if it returned to systemic circulation. Hypothermic perfusion of the liver using UW solution may be effective for preventing hepatic tissue injury during extended hepatectomy with hepatic vascular occlusion.

Adenosine↗

Expression of hypoxia inducible factor-1alpha during liver regeneration induced by partial hepatectomy in rats.

BACKGROUND/AIMS: It has been well established that hypoxia inducible factor-1alpha (HIF-1alpha) transcribes essential factors in cell preservation, including angiogenesis, during hypoxia. However, the transition of HIF-1alpha expression during liver regeneration remains unknown. In this study, a role of HIF-1alpha was experimentally elucidated in relation to sinusoidal endothelial reconstruction during liver regeneration. METHODS: Expression of HIF-1alpha was evaluated in the regenerating liver following 70% hepatectomy in rats. Expressions of nuclear HIF-1alpha, vascular endothelial growth factor (VEGF) and fms-like tyrosine kinase-1 (flt-1) were measured by Western blot and liver blood flow by a laser Doppler. Sinusoidal endothelial cell area (SECA) and HIF-1alpha were localized by immunohistochemistry. HIF-1alpha mRNA was measured by reverse transcription-polymerase chain reaction. RESULT: Liver blood flow and SECA were lowest 36 and 72 h following hepatectomy, respectively. Nuclear HIF-1alpha peaked at 24 h and continuously increased 72-120 h following hepatectomy. This transition was fully supported by histological HIF-1alpha expression and HIF-1alpha mRNA up-regulation. VEGF and flt-1 peaked at 120 and 12 h, respectively. CONCLUSIONS: A significant evaluation in HIF-1alpha expression was revealed in regenerating rat livers. HIF-1alpha expression was preceded by VEGF and flt-1 expression and thus may be related to sinusoidal endothelial reconstruction.

Animals↗

One sample antipyrine clearance after 90% partial hepatectomy in the rat.

Antipyrine clearance was estimated by a one-sample saliva technique before and after 90% partial hepatectomy in nine rats. For comparison, the hepatic contents of cytochrome P450 and serum alanine amino transaminase activity were determined in vitro. Antipyrine clearance and hepatic cytochrome P450 were reduced according to the reduction in liver weight following hepatectomy. During hepatic regeneration, antipyrine clearance and liver weight increase identically, whereas total cytochrome P450 recovered more slowly, being 71% of initial values at the time when antipyrine clearance and liver weight had recovered. Serum alanine amino transferase activity increased 10-20 times 24 h after hepatectomy, and normalized after 52 h. The hepatic glutathione content per gram liver weight was unchanged during the regeneration, suggesting intact detoxification during hepatic regeneration. This study demonstrates that, although the assessment requires some time, and that a value cannot be attached to a fixed time-point, the one-sample antipyrine saliva clearance is a quantitative in vivo estimate of "functional hepatic mass". The test can easily be applied in animal studies where such a measure is requested.

Alanine Transaminase↗

The streaming liver. V: Time and age-dependent changes of hepatocyte DNA content, following partial hepatectomy.

Two processes contribute to the change in hepatocyte ploidy following partial hepatectomy: one is age-dependent, while the other depends on the time which has elapsed since hepatectomy. While in the normal liver hepatocyte DNA content increases with the age of the cell, following hepatectomy the average DNA content (or ploidy) for the entire population rises as well. Hepatocyte age was derived from the cell's distance from the portal tract. We have previously shown that hepatocytes are formed adjacent to the portal tract and stream toward the terminal hepatic vein, advancing 2 microns/day. This finding enables the estimation of hepatocyte age from its location, since the older a cell the more remote it is from the portal tract. Twenty-four young male random-bred rats were partially hepatectomized and killed in groups of four animals at the following times: 1 h and 1, 2, 3, 7 and 14 days. Liver sections and nuclear suspensions which were collected by fine needle aspiration were stained with Feulgen and measured with the aid of computerized image cytometry. Part of the suspension which was aspirated with a fine needle was stained with propidium iodide and measured by flow cytometry. Both nuclear area and the DNA content increase with the age of the cell. The older a cell, the higher its ploidy. Generally, young hepatocytes which synthesized DNA did also divide, while older cells tended to accumulate DNA and became polyploid. The average nuclear DNA content of the entire population increased by 14% in 3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗