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.     

Liver bacterial clearance following hepatic artery ligation and portacaval shunt

The reticuloendothelial system (RES) plays an important role in removing bacteria, endotoxins, and immune complexes from the circulation. Hepatic phagocytosis accounts for more than 80% of RES function. The dual hepatic blood supply (hepatic artery/portal vein) may be altered by pathologic states and surgical procedures. This study evaluates and compares the effect of hepatic artery ligation and portacaval shunt on hepatic trapping of viable Escherichia coli. Thirty rats were placed in three groups: Group I was composed of sham operated controls; Group II underwent end-to-side portacaval shunt (PCS); and in Group III, hepatic artery ligation (HAL) was performed. At 2 weeks following the operation 10(9) 35S-radiolabeled viable E. coli were injected via the tail vein. At 10 min, bacterial distribution in the different organs was determined. Tissue samples were processed for liquid scintillation counting. The final distribution of bacteria was calculated from the input specific activity (dpm/bacteria) and expressed as the mean percentage of injected viable E. coli per gram of tissue and per organ weight. There was a significant decrease of bacterial trapping by the liver in rats following PCS (Group II), 45.0 +/- 10.4% vs controls 77.1 +/- 3.73% (P less than 0.005). This was partially compensated for by a significant increase of bacterial trapping by the lung. The decreased clearance in PCS rats is due to a reduction in liver mass compared to that in controls. Bacterial localization in HAL (Group III) rats was similar to that in controls. These data show that PCS decreases hepatic clearance and increases pulmonary localization of viable E. coli. This phagocytic dysfunction may contribute to increased susceptibility to infection following portacaval shunt.     

Effects of a somatostatin analogue (SMS 201-995) on hepatic and splenic reticulo-endothelial function in the rat

The effects of a long acting somatostatin analogue, SMS 201-995, on reticulo-endothelial system (RES) activity were studied in rats. Administration of 2 micrograms SMS 201-995 subcutaneously twice a day for 7 days significantly increased the splenic and hepatic uptake of 99mTc-sulphur colloid and damaged 51mCr-red blood cells. Furthermore, SMS 201-995 administration significantly increased the plasma clearance of colloidal carbon as indicated by a lower area under the curve and an increased elimination constant. SMS 201-995 administration also significantly improved survival after intraperitoneal injection of Escherichia coli endotoxin. These results suggest that SMS 201-995 stimulates RES activity in rats. It is suggested that SMS 201-995 may be of value in stimulating RES activity in patients with cirrhosis and portal hypertension.     

肝硬变腹水患者门腔静脉分流术后肾素活性、血管紧张素转换酶及血管紧张素Ⅱ的变化

目的探讨肝硬变腹水患者行门腔静脉分流术前后肾素活性（ＰＲＡ）、血管紧张素转换酶（ＡＣＥ）、血管紧张素Ⅱ（ＡⅡ）水平及门静脉压力（ＰＶＰ）的变化。方法应用光度比色分析和放射免疫分析法,对１６例肝硬变合并腹水的患者行门腔静脉分流术前后和１６例行胃肠道肿瘤切除手术的对照组患者,手前后的门静脉、外周静脉和动脉血中的ＰＲＡ、ＡＣＥ、ＡⅡ及ＰＶＰ进行了测定。结果肝硬变组门腔静脉分流前后的ＰＲＡ、ＡＣＥ、ＡⅡ及ＰＶＰ显著高于对照组（Ｐ＜００５）,分流后的ＰＲＡ、ＡＣＥ、ＡⅡ及ＰＶＰ水平较分流前显著降低（Ｐ＜００５）,肝硬变腹水患者血中ＡＣＥ水平与ＰＶＰ呈明显正相关（Ｐ＜００１）。结论门腔静脉分流术能有效的降低肝硬变腹水患者的ＰＶＰ和ＰＲＡ、ＡＣＥ、ＡⅡ水平,这是导致肝硬变腹水患者术后腹水消失的重要原因。     

肝硬变腹水患者门腔静脉分流术后肾素活性,血管紧张素转换酶？…

目的 探讨肝硬变腹水患者行门腔静脉分流术前后肾素活性（ＰＲＡ）、血管紧张素转换酶（ＡＣＥ）、血管紧张素Ⅱ水平及门静脉压力（ＰＶＰ）的变化。方法 应用光度比色 放射免疫分析法,对１６例肝硬变合并腹水的患者行门腔静脉分流术前后和１６例行胃肠道肿瘤切除手术的且患者,手前后的门静脉、外周静脉和动脉血中的ＰＲＡ、ＡＣＥ、ＡⅡ及ＰＶＰ进行了测定。结果 肝硬变组门腔静脉分流前后的ＰＢＡ、ＡＣＥ、ＡⅡ及ＰＶＰ显著     

Liver function and encephalopathy after partial vs direct side-to-side portacaval shunt: a prospective randomized clinical trial

BACKGROUND: The aim of this study was to determine, in a prospective randomized clinical trial, whether the partial portacaval shunt offers any advantage in terms of liver function and encephalopathy rate when compared with direct side-to-side direct portacaval shunt. METHODS: Forty-six "good risk" patients with cirrhosis and with documented variceal hemorrhage were randomly assigned to either a partial shunt procedure (achieved by 10-mm diameter interposition portacaval H-graft) or direct small-diameter side-to-side portacaval anastomosis. RESULTS: Operative mortality was zero in both groups. During the follow-up period, encephalopathy developed in 3 patients in the partial shunt group and 9 in the direct shunt group (P =.04). Kaplan-Meier analysis demonstrated that encephalopathy-free survival was significantly longer in the partial shunt group (P =.025). Direct shunt patients had significant hepatic functional deterioration postoperatively compared with the partial shunt group. CONCLUSIONS: The partial portacaval shunt effectively controls variceal hemorrhage. Compared with direct side-to-side portacaval shunt, partial shunt preserves long-term hepatic function and minimizes postoperative encephalopathy. We conclude that the partial portacaval shunt is the preferred approach over direct shunts for patients with cirrhosis and with variceal bleeding.     

A casue of hepatic encephalopathy after portacaval shunt

The intestinal absorption of ammonia and D-xylose was studied under following conditions, i.e. Group 1: patent end-to-side portacaval shunts, Group 2: complete interruption of the portal vein, Group 3: constriction of the portal vein with minimal portal flow into the liver and Group 4: control. The concentration of ammonia and D-xylose in peripheral and portal blood was highest in group 1, but lowest in group 2. The two hour intestinal absorption rate of ammonium citrate and D-xylose was also highest in group 1 (80 per cent), but lowest in group 2 (40 per cent). Therefore, the reduced portal vein pressure after portacaval shunt seems to enhance intestinal absorption of cerebral toxins such as ammonia leading to hepatic encephalopathy after portacaval shunt in cirrhotic patients.     

Liver arterialization prevents thrombocytopenia after portacaval shunt in rats

A low platelet count is a common finding in liver cirrhosis. Clinical practice has shown that a variable number of cirrhotic patients in whom portasystemic shunting procedures have been performed does not recover from thrombocytopenia: this observation questions the role that portal hypertension may have in maintaining the low platelet count. We have previously described the appearance of thrombocytopenia in rats submitted to portacaval shunt 1 month after the operation. In the present study we have investigated a supposed protective influence of a good liver function in maintaining a normal thrombocytopenia: 56 male Wistar rats were divided into 4 groups: group A (15 rats) sham-operated; group B (16 rats) submitted to portacaval shunt (PCS); group C (17 rats) submitted to PCS plus arterialization of the portal stump by the right renal artery, and group D (8 rats) submitted to PCS plus right nephrectomy. Group B (PCS) and D (PCS plus right nephrectomy) showed a marked thrombocytopenia, whereas group A (sham-operated) and C (PCS plus liver arterialization) evidenced a normal platelet count. These results strongly support the hypothesis that a low platelet count can ensue during a chronic liver disease in the absence of portal hypertension and that restoration of the hepatic blood flow can prevent thrombocytopenia.     

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.     

门腔静脉侧仙分流加肝动脉强化灌注对肝硬变肝脏影响的实验研究

目的 门腔分流术严重影响肝脏血循环,为改善术后肝供血,设计并进行了门腔分流加肝动脉强化灌注术的实验研究。方法 ４８只Ｗｉｓｔａｒ大鼠被随机均分为：正常对照组（Ⅰ组）,肝硬变对照组（Ⅱ组）,肝硬变分流组（Ⅲ组）,肝硬变分流加肝动脉强化灌注组（Ⅳ组）;行肝功能检查,肝活检及核素动态肝胆显像。结果 Ⅳ组较Ⅲ组肝功能明显改善（Ｐ〈０．０５）。核素显像：高峰时间提前（Ｐ〈０．０５）;排泄率增高（Ｐ〈０．０１     

Hepatic haemodynamic changes after portacaval anastomosis in normal, cirrhotic and chronic prehepatic portally hypertensive rats

Radioactive microspheres were used to determine the hepatic haemodynamic response to portacaval anastomosis in normal, cirrhotic and chronic prehepatic portally hypertensive rats 20 days after operation, and in normal rats 2 months after operation. After 20 days portacaval anastomosis caused a decrease in liver mass only in normal and cirrhotic animals, whereas hepatic arterial blood flow per unit of mass increased in normal (+488 per cent), cirrhotic (+191 per cent) and prehepatic portally hypertensive rats (+133 per cent). Despite these facts, animals with portacaval anastomosis showed a reduced hepatic total perfusion (arterial plus portal inflow) per unit of mass with respect to controls in normal (-53 per cent) and cirrhotic rats (-68 per cent), but not in those with prehepatic portal hypertension. Comparing studies carried out at 2 months with those performed 20 days after portacaval anastomosis in normal rats, some recovery of liver mass and total liver blood flow was observed. In conclusion, portacaval anastomosis produced a limited increase in hepatic arterial blood flow which was unable to preserve liver mass and its total perfusion in normal and cirrhotic animals. In contrast, portacaval anastomosis did not significantly alter liver mass or its perfusion in animals with chronic prehepatic portal hypertension, as both values were previously diminished in controls. Thus, the risk of liver failure after portacaval anastomosis is higher in normal and cirrhotic rats than in those with chronic prehepatic portal hypertension.     

Hepatic organic anion transport following portacaval shunt in patients with cirrhosis

In patients with cirrhosis and bleeding esophageal varices, serum bilirubin level usually increases shortly after portasystemic anastomosis. The aim of the present study was to determine whether a change of the functional reserve capacity of the liver to store or excrete organic anions contributes to this post-shunt hyperbilirubinaemia. For this purpose, the relative hepatic storage capacity (S) and maximal biliary excretory rate (Tm) of bromsulphalein sodium (BSP) were estimated before and after elective portacaval shunts. Studies were performed in 13 cirrhotic patients who received less than 2 units of blood transfusion during the shunt procedure and none afterwards. S and Tm of BSP were determined preoperatively and 4 and 14 days after end-to-side portacaval shunt. Before shunt, S and Tm were significantly less in cirrhotic patients than in individuals with normal liver function. A further decrease of these values occurred 4 days after the shunt, suggesting that the deprivation of portal blood decreased the ability of liver to excrete organic anions. Two weeks postoperatively, S and Tm values were not different from the preoperative data demonstrating a recovery of organic anion transport capacity within a relatively short interval. The present data show that portacaval shunts temporarily reduce the organic anion excretory capacity of the cirrhotic liver. Therefore, large anion load, such as bilirubin derived from increased hemolysis, may temporarily saturate the excretory system, thereby inhibiting the elimination of other, potentially toxic, organic anions.     

Therapeutic efficacy of the transplantation of isolated hepatocytes in rats with surgically induced acute hepatic failure: a study of the mechanism

In this study, the beneficial effect of intrasplenic transplantation of hepatocytes or splenocytes was shown in animals with 75% hepatectomy and portacaval shunt but not in animals with total dehepatization by hepatic vascular exclusion. No enhancement of the phagocytic activity was observed in the animals with 75% hepatectomy and portacaval shunt after injection of hepatocytes or splenocytes. This study confirms the efficacy of hepatocytes for the treatment of experimental liver failure but shows that nonhepatic cells may be equally as effective. Metabolic activity of the transplanted cells and stimulation of the phagocytic activity of the reticuloendothelial system probably do not explain the therapeutic effect of the transplanted cells.     

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.     

Effects of portacaval shunt and hepatic artery ligation on liver surface oxygen tension and effective hepatic blood flow

Liver surface oxygen tension (LSOT) and nutrient hepatic blood flow (NHBF) were measured in rats 1 hr and 1 week after sham operation, portacaval shunt (PCS), and hepatic artery ligation (HAL). LSOT was measured using a heated Clark electrode (37 deg) and was expressed as percentage of rectus muscle O2 tension to correct for changes in systemic oxygenation. Nutrient hepatic blood flow (NHBF) was measured using steady-state, low-dose galactose clearance pharmacokinetics. Acutely, we found a close correlation between LSOT and nutrient hepatic blood flow after both hepatic artery ligation and portacaval shunt. At one week after hepatic artery ligation, LSOT and nutrient hepatic blood flow made parallel increases. However, 1 week after portacaval shunt, LSOT increased while nutrient hepatic blood flow remained reduced. The divergence in these results between the two methods of producing hepatic hypoperfusion, implies that LSOT recovers via a different mechanism after portacaval shunt. Recovery of LSOT at one week probably reflects normalization of hepatic O2 delivery after hepatic artery ligation and impaired oxygen utilization after portacaval shunt.     

Effects of portacaval shunt and portacaval transposition on hepatocellular and hepatic reticuloendothelial cell activity in the dog

Quantitative reduction of portal blood flow following a portacaval shunt (PCS) adversely affects hepatocyte function, but does not alter HRES activity[L.P. Edgcomb, J.A. Knol, and F.E. Eckhauser. J. Surg. Res.33: 233, 1982]. To determine whether similar changes occur after qualitative alteration of portal blood flow, portacaval transpositions (PCT) were constructed in six conditioned mongrel dogs. Estimated hepatic blood flow (EHBF) was determined scintigraphically by the rate of hepatic uptake of a 500-μCi dose of ^99mTc-sulfur colloid (Tsc). Hepatic reticuloendothelial cell (RES) phagocytic (PI) and degradative (DI) indices were calculated from the half-time blood disappearance of ¹³¹I-labeled RES test lipid emulsion, and the half-time urine appearance of free ¹³¹I, respectively. Opsonic activity (OI) was determined by gelatin latex particle agglutination and normalized to control values. Hepatocellular function was assessed by serial determinations of albumin (Alb), and pyruvic and glutamic oxaloacetic transaminases (SGPT and SGOT). All studies were performed prior to and at 3, 6, and 9 weeks following PCS or PCT. Conclusions: In the dog, neither PCS nor PCT adversely affected HRES activity. Hepatocellular function and OI remained unchanged following PCT but deteriorated significantly after PCS. Observed changes in hepatocyte function and OI following PCS suggest that hepatocellular integrity and serum opsonic activity may be interrelated.     

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.     

Treatment of post-hepatectomy hepatic cellular energy crisis in cirrhosis with ATP-MgCl2 administration

The present study was undertaken to investigate the effect of ATP-MgCl2 for hepatic cellular energy crisis following hepatectomy in cirrhosis. In experimental study, cirrhotic rats, induced by subcutaneous injection of CCl4 twice a week for 10 weeks, received ATP-MgCl2 (12.4 mumoles) (ATP group) or saline (control group) at 2 hours after 68% hepatectomy. The hepatic cellular energy charge (EC) and arterial ketone body ratio (AKBR), which were good indicators to evaluate the hepatic cellular metabolism, and reticuloendothelial system (RES) function were significantly improved among ATP group at 24 hours after hepatectomy compared to the control group. Survival at one week was also significantly improved with ATP-MgCl2 treatment. In clinical study, ATP-MgCl2 (30-50 mumoles/kg) was infused intravenously to twenty hepatectomized cirrhotic patients. The hepatic cellular energy metabolism, studied using AKBR, and RES function as well as the clinical course were improved with ATP-MgCl2) treatment compared to those of the conventionally treated controls. These data indicate that ATP-MgCl2 is beneficial as one of the therapeutic approaches to improve the hepatic cellular energy crisis after hepatectomy which is the major cause of death following hepatectomy among cirrhotic patients.     

Endogenous endotoxemia in patients with liver cirrhosis —A quantitative analysis of endotoxin in portal and peripheral blood

In order to investigate the mechanism of endogenous endotoxemia (that is, endotoxemia observed in the absence of infection) in patients with liver cirrhosis, the concentration of endotoxin in the portal (PO-Et) and peripheral blood (PE-Et) from fifty three patients undergoing abdominal surgery was simultaneously measured by a quantitative endotoxin assay. The PE-Et of the patients with liver cirrhosis (19.8±20.2 pg/ml, n=23) was significantly elevated, when compared with that of the patients without liver cirrhosis (9.2±5.1 pg/ml, n=30), and was close to the normal range of PE-Et obtained from thirty healthy volunteers (7.2±4.1 pg/ml, n=30). The PO-Et was also higher in the patients with liver cirrhosis than in the patients without liver cirrhosis. Moreover, PO-Et was significantly higher than PE-Et in all the patients (p<0.05). The per cent difference in the endotoxin concentration between the portal and peripheral blood (percentage of ΔEt) was significantly decreased in the cirrhotic patients, especially in those with esophageal varices, which was well correlated with the phagocytic activity of the reticuloendothelial system (RES) determined by the clearance of iron colloid. The endogenous endotoxemia is thus likely to be due to the impaired clearance of endogenous endotoxin in portal blood, resulting from both the decreased phagocytic activity of RES in the liver and the coexisting porta-systemic bypass.     

Endogenous endotoxemia in patients with liver cirrhosis--a quantitative analysis of endotoxin in portal and peripheral blood

In order to investigate the mechanism of endogenous endotoxemia (that is, endotoxemia observed in the absence of infection) in patients with liver cirrhosis, the concentration of endotoxin in the portal (PO-Et) and peripheral blood (PE-Et) from fifty three patients undergoing abdominal surgery was simultaneously measured by a quantitative endotoxin assay. The PE-Et of the patients with liver cirrhosis (19.8 +/- 20.2 pg/ml, n = 23) was significantly elevated, when compared with that of the patients without liver cirrhosis (9.2 +/- 5.1 pg/ml, n = 30), and was close to the normal range of PE-Et obtained from thirty healthy volunteers (7.2 +/- 4.1 pg/ml, n = 30). The PO-Et was also higher in the patients with liver cirrhosis than in the patients without liver cirrhosis. Moreover, PO-Et was significantly higher than PE-Et in all the patients (p less than 0.05). The per cent difference in the endotoxin concentration between the portal and peripheral blood (percentage of delta Et) was significantly decreased in the cirrhotic patients, especially in those with esophageal varices, which was well correlated with the phagocytic activity of the reticuloendothelial system (RES) determined by the clearance of iron colloid. The endogenous endotoxemia is thus likely to be due to the impaired clearance of endogenous endotoxin in portal blood, resulting from both the decreased phagocytic activity of RES in the liver and the coexisting porta-systemic bypass.