Effect of biliary decompression on reticuloendothelial function in jaundiced rats.

The recovery of reticuloendothelial system (RES) function following decompression of obstructive jaundice was studied using a rat model with bile duct ligation and side-to-side choledochoduodenostomy. Histopathological changes in the liver were still present 5 weeks after relief of jaundice, while results of liver function tests had returned to normal. RES function evaluated by the blood clearance and organ uptake of radiolabelled Escherichia coli using a corrected phagocytic index gradually returned to normal following biliary decompression. The severely impaired RES activity noted 1 week after operation may explain the increased incidence of sepsis and renal insufficiency in the early period after biliary surgery in jaundiced patients.     

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.     

The three different phases of reticuloendothelial system phagocytic function in rats with liver injury

In the present study, reticuloendothelial system (RES) phagocytic function of rats with partial hepatectomy or experimentally induced liver cirrhosis was investigated by determining the phagocytic index, the opsonic index, and uptake rate in liver, spleen, and lung of a 51Cr-labeled endotoxin-injected rat. In both the partially hepatectomized and the cirrhotic rats, all three indicators varied markedly according to the elapsed period since liver injury. The changes in RES phagocytic function were classified into three different phases: compromised, compensatory, and enhanced. The compromised phase, consisting of a decrease in the phagocytic index, was observed during the first 24 hr after 67% hepatectomy and in advanced liver cirrhosis. This represented the failure of RES phagocytic function. The compensatory phase, in which the phagocytic index was maintained at nearly normal levels mainly by a compensatory enhancement in the opsonic index, was seen during the first to second postoperative day and in moderate liver cirrhosis. The enhanced phase, with a high phagocytic index, was observed from Day 4 to approximately Day 14 after surgery, and in the cases of mild liver damage. In the compromised and compensatory phases, the liver uptake rate was significantly decreased compared with the control. However, the uptake in the spleen and lung were markedly increased. In conclusion, the phagocytic function of the RES was significantly affected to a degree which changed with the extent of liver damage.     

The adaptive response of the reticuloendothelial system to major liver resection in humans

OBJECTIVE: To evaluate the contribution of the liver to total circulatory reticuloendothelial system (RES) phagocytosis capacity in patients undergoing liver resection and to compare it with values in end-stage chronic liver disease. SUMMARY BACKGROUND DATA: The mechanism whereby major liver resection is associated with a high incidence of infection is unknown. Significant impairment of RES phagocytosis has been described in liver failure, rendering such patients susceptible to infection; and we hypothesized that similar impairment might occur following major liver resection. METHODS: A prospective study was conducted in which Tc-albumin microspheres blood clearance served as a parameter for RES phagocytosis and was studied together with indocyanine green blood clearance, actual liver volume measured by three-dimensional image analysis, and a clinical score of hepatic dysfunction in 17 patients undergoing liver resection and in 8 patients with end-stage chronic liver disease assessed for liver transplantation. RESULTS: When expressed relative to volume unit of residual liver, microspheres clearance increased significantly in the immediate postoperative period (day 1) following major (0.009% versus 0.022% min(-1) mL(-1), P < 0.001), but not minor liver resection. In contrast, the absolute rate of microsphere clearance decreased following major resection (15% min(-1) versus 10% min(-1), P < 0.001) and was comparable with the rate observed in end-stage chronic liver disease (9% min(-1)). This decrease in circulatory microspheres clearance after resection paralleled a decrease in indocyanine green clearance (R2 = 0.511, P = 0.006), and there was a trend for those with moderate liver dysfunction to have lower microspheres clearance rates (P = 0.068). CONCLUSION: Preservation of a minimum volume of functioning liver is a prerequisite for adequate RES phagocytosis capacity, and failure of this system may predispose patients undergoing major liver resection to infection as observed in clinical studies.     

Antibody to endotoxin core glycolipid reverses reticuloendothelial system depression in an animal model of severe sepsis and surgical injury

To study the effect of severe sepsis on the function of the reticuloendothelial system (RES) we have measured the clearance kinetics and organ distribution of both low-dose technetium tin colloid (TTC) and 75selenomethionine-labelled E. coli in rabbits 24 hours after either sham laparotomy or appendix devascularization. Sepsis resulted in similar delayed blood clearance and reduced liver (Kupffer cell) uptake of both TTC and E. coli. To investigate the ability of polyclonal antibody to E. coli-J-5 (core glycolipid) to improve RES function in the same model of sepsis, further animals were pretreated with either core glycolipid antibody or control serum (10 ml IV) 2 hours before induction of sepsis. TTC clearance kinetics were determined 24 hours later. Antibody pretreated animals showed: a reduced incidence of bacteremia; normalization of the rate of blood clearance and liver uptake of TTC; and a 'rebound' increase in splenic uptake of TTC. We conclude that antibody to E. coli-J-5 enhances bacterial clearance by the RES.     

Bacterial clearance in the intact and regenerating liver

The Kupffer cells in the liver play an important role in reticuloendothelial system (RES) function by clearing particulate matter and bacteria from the blood stream. While hepatocyte regeneration and function have been extensively studied following partial hepatectomy, little information is available concerning RES function in the regenerating liver. This study investigates hepatic RES function by evaluating bacterial clearance (live E. coli) in the intact and regenerating liver. Thirty-four young male Sprague Dawley rats were studied. Twenty-two animals underwent a standard 70% partial hepatectomy using ligature technique and 12 had a sham operation. Both groups of rats received 10(9) organism of S35 labeled E coli, intravenously at 24 hours, 72 hours, 2 1/2 weeks, and 6 weeks postoperatively. Rats were killed 10 minutes following injection and liver, lung, spleen, and kidney harvested, fixed, and radioactivity was determined using a scintillation spectrometer interfaced with a micro-computer counting the S35 radiolabel. The total organ count of trapped bacteria in liver in partially hepatectomized rats was lower than intact controls at 24 hours (22.0% v 46.4%, P less than .01), but was similar at 72 hours, 2 1/2 weeks, and 6 weeks. Partial hepatectomy increased the amount of bacterial trapping in the lung at 24 hours (11.3% v 1.7%, P less than .01) and 72 hours (10.1% v 1.7%, P less than .05) and returned to normal at 2 1/2 weeks and 6 weeks. Splenic activity was increased following hepatectomy at 2 1/2 weeks. Renal clearance was increased at 72 hours and 2 1/2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)     

The influence of biliary obstruction and sepsis on reticuloendothelial function in rats.

Obstructive jaundice is frequently associated with septic complications and renal impairment. The present study was performed in order to evaluate reticuloendothelial system (RES) function in obstructive jaundice and the influence of a septic challenge. Male Sprague-Dawley rats were allocated into four groups (laparotomy alone, caecal ligation and puncture (CLP), ligation of the common bile duct (CBD) alone and CBD+CLP, respectively). Mortality, blood clearance and organ distribution of 125I labelled Escherichia coli were determined. Mortality in sepsis (CLP) significantly increased in jaundiced animals (p less than 0.033). Blood clearance of radiolabelled E. coli was significantly impaired in both jaundiced groups. In jaundiced animals, hepatic localisation and renal uptake of E. coli significantly increased (p less than 0.001), while radioactive counts in bile significantly decreased (p less than 0.01). Changes in organ distribution of bacteria did not depend on alterations in blood flow. Thus, RES function was impaired in jaundiced animals and mortality increased in a concomitant septic challenge in jaundiced animals.     

Influence of dextran on blood clearance and organ distribution of radiolabelled E. coli and on survival in experimental E. coli septicemia

Previous reports indicated impaired function of the reticuloendothelial system following administration of dextran. In the present experimental study, intravenous injection of Escherichia coli resulted in four deaths among 15 rats pretreated with i.v. dextran 70, but none in 15 controls (p less than 0.05). To evaluate the influence of dextran on bacterial clearance from blood and distribution in organs, 125I-labelled, heat-killed E. coli was injected 1 or 24 hours following i.v. injection of 1.0 ml sterile saline solution or 1.0 ml dextran 70. After both of these intervals, dextran resulted in significant (p less than 0.05) decrease of blood clearance compared with the controls. The organ distribution in counts/minute (cpm)/g tissue was compared in liver, spleen and lungs. Splenic uptake was reduced at both times following dextran administration, while there was increase in pulmonary uptake at 1 hour and in hepatic uptake at 24 hours post-dextran (p less than 0.005 and p less than 0.02, respectively). Evaluation of cpm/total organ weight showed no change after dextran injection, except for increased (p less than 0.05) pulmonary uptake after 1 hour.     

Experimental and clinical studies on the effect of reticuloendothelial system (RES) potentiator in the depressed RES function in cirrhotics

Among the patients with liver cirrhosis (LC) who undergo the operation, the postoperative complications are not infrequent and sometimes prove fatal. The impaired hepatic function, especially the impaired reticuloendothelial system (RES) function, has been claimed to be a possible pathogenic factor for these complications. The present experimental and clinical studies were undertaken to investigate the RES function and the effect of preoperative OK-432 administration as an RES potentiator in LC. The results are as follows: 1) CCl4-induced LC rats were evaluated for RES global phagocytic function, Kupffer cell phagocytic function, plasma opsonic activity and plasma opsonic substances such as fibronectin, C3 and IgG. All parameters except IgG showed significant depression compared to those values in normal rats. However, the administration of OK-432 (0.1 KE/rat, ip) improved all these depressed parameters. The OK-432 administration also significantly improved the survival following panperitonitis in LC rats. 2) Among 18 LC patients with hepatocellular carcinoma undergoing partial hepatectomy, the RES global phagocytic function, plasma opsonic activity and plasma opsonic substances were evaluated. Same as the experimental study, all parameters except IgG were significantly depressed among the LC patients compared to those values in the patients with normal liver. However, the preoperative OK-432 administration (5 KE/day sc for 4 days) significantly improved these parameters and consequently decreased the postoperative complications. These results indicate that the preoperative RES activation by the OK-432 was effective and useful for the prevention of the postoperative complications in the LC patients.     

Reticuloendothelial system blockade promotes progression from mild to severe acute pancreatitis in the opossum

OBJECTIVE: To examine the relation between hepatic reticuloendothelial system (RES) dysfunction and the development of acute biliary pancreatitis. In an opossum model, the authors tested the hypothesis that RES blockade can turn the mild pancreatitis seen after pancreatic duct obstruction (PDO) into the severe form. SUMMARY BACKGROUND DATA: Biliary obstruction is considered the decisive event in gallstone pancreatitis. Suppression of the RES occurs during biliary obstruction. METHODS: Eighteen opossums were placed into three groups of six animals each: group A, RES blockade with lambda-carrageenan; group B, PDO; and group C, PDO and RES blockade with carrageenan. The severity of pancreatitis was evaluated by enzyme serum levels and percentage of pancreatic tissue necrosis. RES capacity was measured by dynamic liver scintigraphy, and hepatic blood flow was documented using the hydrogen clearance technique. RESULTS: No changes in hepatic blood flow occurred in groups A to C. RES capacity was suppressed in groups A and C; in group B, RES function remained unchanged. In group A, amylase and lipase levels remained normal, 3 +/- 1.9% of pancreatic tissue were necrotic. The animals in group B developed mild edematous pancreatitis with an increase in amylase and lipase levels and 15 +/- 10% of pancreatic necrosis. In group C, amylase and lipase increased significantly and histology revealed severe necrotizing pancreatitis, with 72 +/- 11% of necrotic areas. CONCLUSIONS: Artificial RES blockade can promote the progression from mild pancreatitis as observed after PDO to the severe necrotizing form of the disease. Thus, RES dysfunction resulting from biliary obstruction might be an important cofactor in the pathogenesis of bile-induced pancreatitis.     

Graft function and survival depend primarily on host factors in compromised recipient models of orthotopic liver transplantation in the rat

BACKGROUND: Experimental models of liver transplantation use normal recipients, although most patients undergoing liver transplantation suffer from acute or chronic liver failure. This study was designed to analyze the outcome of orthotopic liver transplantation in compromised rat hosts. METHODS: Recipient animals were either rats with D-galactosamine-induced acute or rats with chronic liver failure secondary to common bile duct ligation. Liver damage was evaluated by monitoring enzymes, bilirubin, ammonia levels, prothrombin, thrombin time, and cytokines. In vivo function of hepatocytes and sinusoidal endothelial cells were evaluated by indocyanine green and hyaluronic acid uptake. Transplantation was performed in normal, acute, and chronic liver failure rats at different time points using either freshly harvested or cold-preserved syngeneic livers. RESULTS: Survival with fresh grafts decreased significantly when transplants were performed 48 hr after the induction of acute liver failure. No rats with acute liver failure survived transplantation with grafts stored for 12 or 24 hr although in chronic failure survival was more 80%. Survival of acute liver failure rats receiving 6 hr preserved grafts was 16.6% compared with 83.3% observed with fresh grafts transplanted at the same time point after D-galactosamine injection. Elevated tumor necrosis factor-alpha and interleukin-1beta levels as well as impaired sinusoidal endothelial cell function were detected in acute liver failure rats with 6 h preserved grafts. CONCLUSION: These results suggest that preoperative status and different host factors have a significant effect on outcome and graft function after liver transplantation in rats.     

Detrimental effect of sinusoidal overperfusion after liver resection and partial liver transplantation

Abstract Liver resection exposes the remaining sinusoids to an over-proportional blood flow. This mechanism may aggravate ischaemia/ reperfusion damage and rejection in partial liver transplants. We studied the potential relevance of this mechanism for the pathogenesis of partial liver transplant dysfunction. Eighty-four isogeneic Lewis rats were divided into four groups: (I) sham operation; (II) partial liver resection (30% residual liver volume); (III) orthotopic transplantation of a full-size liver; (IV) transplantation of a reduced-size liver (30% transplant volume). Microcirculation was determined by intravital microscopy 90 min after surgery. Survival rates, liver function and morphology were monitored over a period of 14 days. Lowest survival rates and impaired liver function were observed after partial liver transplantation (group IV). These transplants displayed the lowest perfusion rate and an increased rate of leukocyte-endothelium interactions in the presence of a significantly increased sinusoidal blood flow velocity compared with those in groups I and III. Sinusoidal overperfusion in groups II and IV resulted in widespread endothelium lesions. Sinusoidal overperfusion seems to be a significant factor impairing liver function after liver resection. In addition to other adverse factors, such as ischaemia/ reperfusion injury, it can contribute to the pathogenesis of postoperative dysfunction of partial liver transplants.     

Detrimental effect of sinusoidal overperfusion after liver resection and partial liver transplantation

Liver resection exposes the remaining sinusoids to an over-proportional blood flow. This mechanism may aggravate ischaemia/reperfusion damage and rejection in partial liver transplants. We studied the potential relevance of this mechanism for the pathogenesis of partial liver transplant dysfunction. Eighty-four isogeneic Lewis rats were divided into four groups: (I) sham operation; (II) partial liver resection (30% residual liver volume); (III) orthotopic transplantation of a full-size liver; (IV) transplantation of a reduced-size liver (30% transplant volume). Microcirculation was determined by intravital microscopy 90 min after surgery. Survival rates, liver function and morphology were monitored over a period of 14 days. Lowest survival rates and impaired liver function were observed after partial liver transplantation (group IV). These transplants displayed the lowest perfusion rate and an increased rate of leukocyte–endothelium interactions in the presence of a significantly increased sinusoidal blood flow velocity compared with those in groups I and III. Sinusoidal overperfusion in groups II and IV resulted in widespread endothelium lesions. Sinusoidal overperfusion seems to be a significant factor impairing liver function after liver resection. In addition to other adverse factors, such as ischaemia/reperfusion injury, it can contribute to the pathogenesis of postoperative dysfunction of partial liver transplants.     

Effect of viable isolated hepatocytes or hepatocyte fractions on survival rate following galactosamine-induced acute liver failure

Administration of galactosamine to rats results in an acute liver failure. The dose-effect relation appeared to be highly strain-dependent. Intraperitoneal injection of 1,000 mg/kg galactosamine resulted in a 90% lethal acute liver failure in Wag/Rij rats. Transplantation of viable isolated hepatocytes, administration of homogenate or cytosol of normal or regenerating liver tissue, or administration of cell-free liver cell culture supernatant did not improve the survival rate in this model of acute liver failure. These findings, which are in striking contrast with the data reported in the literature, are discussed in relation to the specific properties of this type of experimental model for acute hepatic failure.     

Experimental study of endotoxemia and reticuloendothelial system in hepatectomized cirrhotic rats

To investigate acute hepatic failure associated with endotoxemia and reticuloendothelial system (RES) in hepatectomized cirrhotic patients, lipopolysaccharide (LPS) at the dose of 0.2 micrograms/100gBW was injected intravenously into the 70% hepatectomized three groups of rats as follows; LC: rats with thioacetamide-induced liver cirrhosis, Control: rats with normal liver, LC + FN: cirrhotic rats with intravenous supplementation of fibronectin. 1) The survival rates at 24 hours after hepatectomy of each group of LC, Control and LC + FN were 0%, 100%, and 80%, respectively. Residual liver of group-LC revealed massive necrosis in histological study. 2) Phagocytic index (K) of injected 3H-labeled LPS were 0.100/min, 0.155/min and 0.146/min, respectively. 3) Uptake of injected 3H-labeled LPS at 15 minutes after injection was remarkably elevated into the liver compared with the lung and spleen in each group. Also uptakes into the liver per gram of tissue were 0.96% ID/g, 3.00% ID/g and 1.46% ID/g, respectively, and those per total organ were 5.95% ID/TO, 8.20% ID/TO and 9.21% ID/TO, respectively. 4) Level of plasma fibronectin decreased and that of serum total bile acid increased remarkably after injection of LPS in group-LC compared with the others. These results suggest the mortality of hepatic necrosis by LPS in group-LC is attributed to markedly reduced RES function especially in the liver, and supplementation of fibronectin decreases the mortality by enhancing RES function.     

Effect of chronic interleukin-2 treatment on RES phagocytic activity in the rat.

The effect of chronic interleukin-2 (IL-2) injection upon reticuloendothelial system (RES) function in the rat has been determined. Seven-day treatments with two doses of human recombinant IL-2 resulted in a dramatic reduction in the phagocytic uptake of the liver and spleen, while increasing the weight of both organs. There were dramatic histological changes in the intestine, liver and spleen as well. These results suggest that the chronic use of IL-2 can result in hepatic dysfunction, which is associated with altered RES phagocytic function.     

Portal vein arterialization for the treatment of post resection acute liver failure in the rat

INTRODUCTION: Hyperoxygenation of the liver has been suggested to improve its regenerative capacity. Thus, this study sought to determine whether an additional supply of oxygenated blood delivered by portal vein arterialization (PVA) was protective against acute liver failure induced by hepatectomy. METHODS: Sprague-Dawley rats (six per each group) were divided to either undergo PVA or be untreated after extended hepatectomy. Liver injury was evaluated by the serum alanine aminotransferase (ALT) levels. Hepatocyte regeneration was assessed by calculating the mitotic index and bromodeoxyuridine staining. The 10-day survival was assessed in separate experimental groups. RESULTS: The pO(2) in portal blood increased significantly following PVA. Serum ALT levels were significantly reduced in arterialized versus nonarterialized rats. PVA promotes liver regeneration. Finally, PVA significantly improved host survival compared to the controls: 90% versus 30%, respectively. CONCLUSION: These data suggested that an additional supply of arterial oxygenated blood through PVA promoted a rapid regeneration, leading to a faster restoration of liver mass after partial hepatectomy in rats. Thus, PVA may represent a novel tool to optimize hepatocyte regeneration.     

Effect of haemolysis on reticuloendothelial system (RES) phagocytic activity in rats

The role of haemolysis of blood in the alterations in the uptake of [99mTc]SC ([99mTc]-sulphur colloid) in vivo in the rat has been examined. When the haemolysed blood (produced by first freezing the blood in liquid nitrogen) was infused into synergenic Lewis rats via the tail vein, there was a significant reduction in the uptake of the [99mTc]SC by the spleen, but lung, liver and kidney uptake remained constant. These results suggest that haemolysis of the blood may play a role in the alterations in RES phagocytic activity observed in the spleen following thermal injury.     

Acute respiratory failure after hepatic resection in canine biliary obstruction model

Acute respiratory failure after hepatic resection, especially in case of concomitant liver dysfunction, is the most troublesome postoperative complication. In order to clarify the pathophysiological mechanism of acute respiratory failure, EVLW (extravascular lung water) was measured by double indicator dilution method in canine model. Mongrel dogs underwent laparotomy and the common bile duct was ligated and divided. After 6 weeks, EVLW was significantly elevated compared with that of normal dogs (p less than 0.05). From 4 hours after 70% hepatic resection dextran-40 was loaded to increase PWP (pulmonary wedge pressure). EVLW was increased accompanying the elevation of PWP in all groups, but in the group with biliary obstruction EVLW was significantly increased for the same elevation of PWP. These results suggest that permeability of pulmonary capillary was highly increased after hepatic resection in biliary obstruction group. Pulmonary edema in this canine model seems to resemble ARDS in human and the pathophysiological mechanism was thought to be related with depression of RES phagocytic function, activation of complement system and pulmonary vascular plugging by aggregates of degenerating granulocytes and endothelial injury. Gabexate mesilate blocked the increase of the lung vascular permeability and was thought to be effective to protect the lung from postoperative acute respiratory failure.     

Experimental study on the changes of bile acids and their fractions after liver ischemia

Serum bile acids and their fractions in the systemic and portal vein were measured after liver ischemia of 0, 30, 60, and 90 minutes with extracorporeal venous bypass in 20 dogs. The following results were obtained: 1) Total concentration of bile acids in the serum rapidly increased during the ischemic phase because of extinction of enterohepatic circulation due to flow of portal blood into the systemic circulation. 2) Portal blood flow decreased after recirculation of the liver, and this decrease was more severe in the 90-minute ischemic group than in the 30- and 60-minute groups. 3) After recirculation, increased bile acids were taken up by hepatocytes, and their concentrations in the systemic vein decreased markedly. The 90-minute ischemic group had a significantly slower rate of decrease compared to the 30- and 60-minute groups. This was due to its significantly lower portal blood flow rate. 4) Hepatocyte dysfunction was suggested in the 90-minute ischemic group, since the uptake of bile acids into the liver, especially dihydroxy- and deconjugated bile acids, significantly decreased. These results indicate that measurement of serum bile acids and their fractions is useful for estimating the liver function after liver ischemia.