The effect of pentoxifylline on the healing of intestinal anastomosis in rats with experimental obstructive jaundice

The aims of this study were (1) to investigate the effect of experimental obstructive jaundice on the healing of intestinal anastomosis, and (2) to investigate the effect of pentoxifylline on the healing of intestinal anastomosis in rats with obstructive jaundice. Obstructive jaundice was induced in rats by the ligation and division of the common bile duct. Four days after this operation, either pentoxifylline or isotonic saline solution was administered intraperitoneally to these jaundiced rats and controls, and then intestinal anastomosis was performed. The concentrations of serum tumor necrosis factor α (TNF-α) and serum triglyceride of jaundiced and nonjaundiced rats were measured, and the quality of healing was evaluated by measuring the bursting preasure and hydroxyproline content of the anastomoses on the fifth and tenth days of anastomotic healing. Obstructive jaundice resulted in an impaired wound healing of the intestinal anastomosis in the rats. The administration of pentoxifylline to the jaundiced rats resulted in better anastomotic wound healing. The beneficial effects of pentoxifylline on anastomotic healing in rats with obstructive jaundice was attributed to its inhibitor effect on the endotoxin-induced TNF-α release from macrophages and monocytes, and the stabilizing effect on the neutrophils. Received: March 29, 1999 / Accepted: March 24, 2000     

Development and reversal of endotoxemia and endotoxin-related death in obstructive jaundice

Gut-derived endotoxemia has been implicated in postoperative complications in patients with jaundice. It is thought that absence of bile in the gut predisposes to portal absorption of endotoxin and endotoxemia is reversed by oral bile salt replacement or internal biliary drainage and return of bile to the gut, but not by external drainage. We believe that the importance of gastrointestinal bile flow has been overestimated and biliary obstruction and the integrity of hepatocyte and Kupffer cell function are more important in the development and reversal of endotoxemia. In experiment 1, serum endotoxin concentrations were measured in control rats (n = 10) after choledochovesical fistula (n = 15) and bile duct ligation (n = 15) and after relief of biliary obstruction by internal drainage (choledochoduodenostomy; n = 8) and sterile external drainage (choledochovesical fistula; n = 8), with a quantitative limulus assay. In experiment 2, mortality rates were measured in similar groups 48 hours after administration of oral endotoxin (5 mg/100 gm) and intravenous lead acetate (5 mg/100 gm). Bilirubin levels were elevated in bile duct ligation (192 +/- 13 mumols/L) compared with control animals and those with choledochovesical fistula, internal drainage, and external drainage (10.6 +/- 1.5 mumols/L). In experiment 1, significant portal endotoxemia and systemic endotoxemia occurred in bile duct ligation (portal, 130.4 +/- 12.9 pg/ml; systemic, 91.8 +/- 11.0 pg/ml) but not in choledochovesical fistula (portal, 49.3 +/- 17.1 pg/ml; systemic, 27.2 +/- 11.5 pg/ml). Relief of obstruction by both internal and external drainage reversed endotoxemia. In experiment 2, significant death occurred in bile duct ligation (13 of 15) but not in choledochovesical fistula (3 of 15), and relief of obstruction by both internal and external drainage prevented death. These results confirm that biliary obstruction is a more important factor than is gastrointestinal bile flow in the development and reversal of endotoxemia.     

Research review: DNA polymerases as molecular markers of the regenerating capacity of hepatocytes

Hepatocyte regeneration has been widely investigated, with the mitotic index and the incorporation of [³H]thymidine being used as regeneration markers. We focused on the induction of DNA replication enzymes, particularly DNA polymerases (pol) α, δ, and ε. Using rat models, we have shown that the activity of pol α in crude liver extract well represents the regenerating capacity of hepatocytes. Using pol α as an indicator, we analyzed liver regeneration in rat models under various conditions: obstructive jaundice, external or internal biliary drainage, and the obstruction of portal vein branches. It has been revealed that the ligation of the common bile duct alone induces a certain amount of hepatocyte proliferation. It was striking that external biliary drainage suppressed regeneration capacity in cholestatic rat liver after partial hepatectomy. The strong regeneration in nonligated lobes induced by portal branch ligation was similar to the liver regeneration seen after partial hepatectomy with respect to the induction of DNA polymerases. Taken together, the aspects of DNA replication, particularly the induction of DNA polymerases, may contribute to shedding new light on the regeneration of human liver. This work was supported in part by a Grant-in-Aid for General Scientific Research and for Cancer Research from the Ministry of Education, Science and Culture, Japan, and by grants from the Uehara Memorial Foundation     

梗阻性黄疸鼠肝脏血红素氧化酶-1及一氧化碳含量的研究

目的 探讨梗阻性黄疸时肝脏血红素氧化酶-1(HO-1)及血浆中一氧化碳(CO)含量的变化。方法 48只 Wistar 大鼠随机分为 4组:假手术对照组(CG)、梗阻性黄疸 7 d组(7 d)、梗阻性黄疸 14 d组(14 d)和梗阻性黄疸 21 d组(21 d),采用免疫组织化学法对肝细胞中 HO-1表达进行分析,应用双波长分光光度计法测定大鼠肝静脉、门静脉及下腔静脉血浆中CO含量。结果 梗阻性黄疸时 HO-1不仅在 Kupffer细胞中表达,而且在肝实质细胞中呈弥漫性表达上调,14 d组和 21 d组肝实质细胞中HO-1表达均较7 d组增加(P<0.01)。梗阻性黄疸各组肝静脉血浆中CO含量较CG组增高(P<0.05,P<0.01);14 d组门静脉血浆中CO含量升高明显,与CG组比较差异有显著性(P<0.05);梗阻性黄疸各组肝静脉血浆中 CO含量与同时间组门静脉血浆中 CO含量相比均显著升高(P<0.01)。梗阻性黄疸各时间组肝静脉CO含量的增高与肝实质细胞中HO-1表达的变化呈显著正相关(P<0.01)。结论 梗阻性黄疸时肝细胞HO-1表达上调致CO产生增多,从而有助于增加肝血流量并减少肝脏功能损害。     

The effect of calcitonin gene-related peptide on healing of intestinal anastomosis in rats with experimental obstructive jaundice

Purpose  Intestinal anastomotic healing is a complex procedure in which several mediators and cytokines play roles. Calcitonin gene-related peptide is an important neuropeptide in inflammation. In this study we aimed to investigate the effect of calcitonin gene-related peptide on healing of intestinal anastomosis in rats with obstructive jaundice. Materials and methods  Obstructive jaundice was induced in rats by the ligation and division of the common bile duct. Four days after the operation, intestinal anastomosis was performed, and either calcitonin gene-related peptide or 0.9% NaCl was administered intraperitoneally to these jaundiced rats and controls. The concentrations of serum tumor necrosis factor-α (TNF-α) and triglyceride levels of all rats were measured, and healing of the anastomosis was evaluated by measuring the bursting pressure and hydroxyproline content on the 7th postoperative day. Results  Calcitonin gene-related peptide was found to have positive effects on healing of the anastomosis by inhibiting the effects of TNF-α and increasing the bursting pressure and hydroxyproline content of the anastomosis. Conclusion  Calcitonin gene-related peptide increases anastomotic wound healing in experimental anastomosis in the presence of obstructive jaundice in rats.     

Study on mechanism of onset of endogenous endotoxemia during obstructive jaundice--with special reference to involvement of biliary infection

To clarify how biliary infections affect onset of endogenous endotoxemia during obstructive jaundice, I tried to review the clinical result of 104 cases of obstructive jaundice, and conducted a Limulus test of portal and peripheral blood in 20 cases of obstructive jaundice and an animal study using 38 rabbits. In cases of obstructive jaundice complicated by biliary infections, clinical improvement of jaundice became significantly unfavorable, and the outcome of surgical operation was significantly inferior to the cases without biliary infections. The endotoxin positive rate in the portal blood of obstructive jaundice was 65% (13 of 20 cases), among which 10 cases (79.6%) was also positive in the peripheral blood. Of these 10 cases, 7 cases manifested endogenous endotoxemia with no infectious focus, and prognosis of these cases was poor. The endotoxin positive rate in portal blood of obstructive jaundice group was also significantly higher than that of non-jaundice group in animal study, and when the reticuloendothelial system was blocked, the endotoxin positive rate in the peripheral blood showed an increasing tendency. In the animal group with experimental cholangitis, all the endotoxin positive animals in the portal blood were also positive in the peripheral blood. This result suggests that biliary infections accelerate a decrease in the reticuloendothelial function during obstructive jaundice. From these results, endogenous endotoxemia seems to affect the onset of various complications during obstructive jaundice and unfavorable prognosis.     

乳果糖和庆大霉素灌胃对梗黄大鼠应激性溃疡的影响

目的 探讨乳果糖和庆大霉素灌胃对梗阻性黄疸(梗黄)大鼠应激性溃疡的影响及可能机制.方法 雄性Wistar大鼠40只随机分4组:A组,结扎胆总管并以乳果糖和庆大霉素灌胃;B组,结扎胆总管并以葡萄糖灌胃;C组,假手术并用乳果糖和庆大霉素灌胃;D组,假手术并用葡萄糖灌胃.先行手术,14 d后再将4组大鼠分别行灌胃7 d,然后以水浸束缚应激诱导建立应激性溃疡模型,并分别检测门静脉血内毒素值和胃黏膜溃疡指数(UI,Guth评分).结果 A组门静脉血内毒素值及UI显著下降,B组门静脉血内毒素值及UI升高;C,D组门静脉血内毒素值及UI均处于较低水平.结论 内毒素血症是加剧梗黄状态下应激性溃疡发生的重要原因之一.乳果糖和庆大霉素灌胃可降低血内毒素水平,有利于降低梗黄大鼠的总体应激性溃疡的发生率.     

Enteral donor pre-treatment with ursodeoxycholic acid protects the liver against ischaemia-reperfusion injury in rats

Abstract Liver donor pre-treatment with ursodeoxycholic acid (UDCA) may protect against injury during transplantation. In the present study we evaluated whether enteral administration of UDCA has an effect on bile flow and protects the liver from injury related to transplantation. Wistar rats were used in liver perfusion (LP) and transplantation (LTx) models. Rats were enterally administered UDCA (800 mg/kg) 3 h before cold perfusion. In LP, bile flow and bile acid composition were analysed. In LTx, serum ALT and liver histology were analysed. LP showed biliary UDCA enrichment up to 36 ± 13% in pre-treated rats, causing higher bile flow ( P = 0.026) compared with control rats. LTx showed lower ALT and TUNEL positive hepatocytes in the UDCA group ( P < 0.02 and P < 0.05). In conclusion, augmented bile salt-dependent bile flow is preserved in the liver after cold storage. Enteral donor pre-treatment with UDCA protects the liver against ischaemia-reperfusion injury.     

Obstructive jaundice associated with extrahepatic portal vein obstruction: Report of two cases

We herein report two cases of obstructive jaundice with markedly dilated collateral veins either in or around the bile duct in the setting of extrahepatic portal vein obstruction (EHPO). In the first case, a proximal splenorenal shunt provided relief of biliary stenosis as well as eradication of esophageal varices due to a decompression of portal hypertension. This evidence proved that the markedly extended collateral veins in the hepatoduodenal ligament caused biliary stenosis by compressing the bile duct. In the second case, obstructive jaundice was probably caused by cholangitis and was relieved with biliary drainage. Portal decompressive surgery was not indicated because of the slight degree of esophageal varices. The relationship between cholangitis and EHPO in these patients calls for further investigation. In cases with EHPO manifesting obstructive jaundice associated with risky esophageal varices, portal decompressive surgery is recommended as the procedure of choice.     

Enteral donor pre-treatment with ursodeoxycholic acid protects the liver against ischaemia-reperfusion injury in rats

Liver donor pre-treatment with ursodeoxycholic acid (UDCA) may protect against injury during transplantation. In the present study we evaluated whether enteral administration of UDCA has an effect on bile flow and protects the liver from injury related to transplantation. Wistar rats were used in liver perfusion (LP) and transplantation (LTx) models. Rats were enterally administered UDCA (800 mg/kg) 3 h before cold perfusion. In LP, bile flow and bile acid composition were analysed. In LTx, serum ALT and liver histology were analysed. LP showed biliary UDCA enrichment up to 36±13% in pre-treated rats, causing higher bile flow (P=0.026) compared with control rats. LTx showed lower ALT and TUNEL positive hepatocytes in the UDCA group (P<0.02 and P<0.05). In conclusion, augmented bile salt-dependent bile flow is preserved in the liver after cold storage. Enteral donor pre-treatment with UDCA protects the liver against ischaemia-reperfusion injury.     

Experimental study on the interruption of hepatic blood flow in obstructive jaundice, with special reference to the causes of death and prolonged jaundice after biliary decompression

The purpose of this investigation was to elucidate the influence of interruption of the hepatic blood flow on survival and on prolonged jaundice after biliary decompression in dogs with obstructive jaundice. There were three experimental groups. Two or three weeks after inducing obstructive jaundice by ligation of the common bile duct with cholecystectomy, the hepatic artery (group A), portal vein (group B) or both (group C) were interrupted for various intervals, with antibiotics administration. Biliary decompression was simultaneously performed with choledochoduodenostomy. The one week survival rate after the interruption of hepatic blood flow was more than 60% at 2 and 1 hours in group A, 20 and 10 minutes in group B, 10 and 5 minutes in group C at two and three weeks after biliary obstruction, respectively. Necrosis more than 50% of the liver was observed in early death cases. Edema and stasis in the bile canaliculi were markedly observed histologically in survivors in groups A and C, accompanied with significant elevations of serum T. Bil and GPT. The changes were greater in cases with longer periods of jaundice. In obstructive jaundice, hepatic artery occlusion causes hepatic necrosis, in spite of antibiotics administration, and may induce prolonged jaundice after biliary decompression. As an indicator of the prognosis, the serum total bile acid value was useful.     

阻塞性黄疸患者肝脏巨噬细胞功能变化的临床研究

为探讨阻塞性黄疸患者围手术期感染发生率明显增高的原因，对３６例阻塞性黄疸患者围手术期肝脏Ｋｕｐｆｆｅｒ细胞吞噬功能和血浆内毒素水平变化进行了观察，并与２０例单纯性胆囊结石患者进行比较。结果显示：胆道梗阻后Ｋｕｐｆｅｒ细胞吞噬功能降低，与对照组比较有显著性差异（Ｐ＜０．０５）；血浆内毒素含量升高，与对照组比较有高度显著性差异（Ｐ＜０．０１）。经手术胆道引流后，血浆内毒素水平则逐渐降低。随着Ｋｕｐｆｅｒ细胞吞噬功能恢复，血浆内毒素进一步降低。由此表明，胆道梗阻后Ｋｕｐｆｅｒ细胞吞噬功能变化与血浆内毒素水平有显著的相关关系。     

Differences in biliary lipid excretion after major hepatectomy in obstructive jaundiced rats with preoperative internal,external, or no biliary drainage

Necessity of preoperative biliary drainage for patients with obstructive jaundice is still controversial. We recently reported that liver regeneration after major hepatectomy was better restored in a rat model of obstructive jaundice with preoperative internal biliary drainage than that without biliary drainage or with external biliary drainage. The aim of this study was to investigate the differences in biliary lipid excretion after hepatectomy in obstructive jaundiced rats with or without preoperative internal or external biliary drainage. After bile duct ligation for 7 days, rats were randomly divided into the three groups; obstructive jaundice-hepatectomy (OJ-Hx), internal biliary drainage-hepatectomy (ID-Hx), and external biliary drainage-hepatectomy (ED-Hx) groups. 70% hepatectomy and internal biliary drainage were carried out 7 days after biliary decompression in the latter two groups and without biliary decompression in the OJ-Hx group. On the day of and on days 1, 2, 3 and 7 after hepatectomy, the liver weight, DNA synthesis rate, biliary lipids excretion rates, and bile acid composition were determined. In the ID-Hx group, the DNA synthesis rate and relative liver weight were significantly higher than those of the OJ-Hx and ED-Hx groups. The excretion rates of biliary lipids were disturbed in the ED-Hx group compared with those in the ID-Hx group and the values in the OJ-Hx group were in-between the ID-Hx and ED-Hx group. The liver regeneration rate was significantly correlated with bile flow and excretion rates of biliary lipids. The maintenance of enterohepatic circulation of biliary lipids before hepatectomy may be important for the liver regeneration.     

Effect of Portal Vein Occlusion on the Pancreas: An Experimental Model

Background The effects of portal vein occlusion on the pancreas are not clearly understood. Therefore, we studied histomorphological changes induced in the rat pancreas by various periods of portal vein occlusion. Materials and methods Sixty female Wistar albino rats were randomly allocated into four groups of 15 each. In Group I (control), rats underwent sham laparotomy to expose the portal vein proximal to its bifurcation. In Groups II–IV, rats underwent laparotomy followed by portal vein occlusion by clamping for 15, 30, and 60 minutes respectively. The pancreas was removed immediately after sham laparotomy in Group I and immediately after clamp release in Groups II–IV. Pancreatic tissue specimens were subjected to histochemical analysis for cell typing and diagnosis, immunohistochemical analysis for identification of the inflammatory markers tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), endothelial nitric oxide synthase (eNOS), and inducible NOS (iNOS), and TUNEL analysis was carried out for identification of apoptotic cells. Results Histochemistry revealed signs of inflammation in pancreatic tissue from rats subjected to portal vein occlusion. Immunohistochemistry revealed that the expression of proinflammatory cytokines TNF-α and IL-1β and the oxidative damage indicator iNOS in rat pancreatic tissue increased progressively with the duration of portal vein occlusion. TUNEL assay revealed no signs of apoptosis in any of the groups. Conclusion We conclude that portal vein occlusion triggers an inflammatory response in the pancreas that worsens the longer the occlusion lasts.     

Biliary bacterial infection in liver surgery

Hepatectomy for biliary tract carcinoma with obstructive jaundice is associated with a higher incidence of postoperative septic complications as compared with hepatectomy for hepatocellular carcinoma or metastatic liver cancer. Since most bacteria isolated from septic sites are identical to those found in the preoperative percutaneous transhepatic biliary drainage (PTBD) bile, bacterial colonization in bile appears to be responsible for posthepatectomy septic complications in patients with biliary tract carcinoma. Although it remains unclear how bile becomes contaminated after bile duct obstruction or why preoperative PTBD increases the incidence of biliary infection, bacterial translocation via the portal vein, resulting from loss of integrity of the intestinal mucosa and change in intestinal microflora, may in part account for the mechanisms. Moreover, impaired function of Kupffer cells and altered structure and function of hepatocyte tight junctions might also participate in the development of postoperative bacteremia in such patients. As septic complications and liver failure are profoundly associated with each other, it is important to take all measures before surgery to enhance liver function and to prevent postoperative septic complications.     

Contribution of portal systemic shunt to Kupffer cell dysfunction in obstructive jaundice

Previous animal models of biliary tract obstruction have shown that hepatic phagocytic activity is impaired secondary to Kupffer cell dysfunction. Biliary tract obstruction leads to portal hypertension and an associated portal systemic shunt. Forty-eight Sprague-Dawley rats were studied to determine the contribution of portal systemic shunt to Kupffer cell dysfunction after 21 days of obstructive jaundice or sham operation. Liver uptake of radiolabeled Escherichia coli decreased from 76.1 +/- 1.4% (sham) to 63.1 +/- 6.1% in the common duct ligation (CDL) rats (P less than 0.05); lung uptake increased from 4.0 +/- 0.6% (sham) to 20.2 +/- 4.5 (CDL) (P less than 0.05). Portal systemic shunt, determined using radioactive microspheres, increased from 2.0 +/- 1.0% (sham) to 46.6 +/- 13.1% (CDL), P less than 0.05. Although a significant portal systemic shunt does exist in this 21-day model of obstructive jaundice, it does not appear to be the only mechanism underlying Kupffer cell dysfunction.     

Beneficial effects of growth hormone and insulin-like growth factor I on intestinal bacterial translocation, endotoxemia, and apoptosis in experimentally jaundiced rats

BACKGROUND: This study was undertaken to investigate the effect of growth hormone (GH) and insulin-like growth factor I (IGF-I), two well-known growth factors, on bacterial translocation, endotoxemia, enterocyte apoptosis, and intestinal and liver histology in a model of experimental obstructive jaundice in rats. STUDY DESIGN: One hundred six male Wistar rats were divided into five groups: I (n = 21), controls; II (n = 22), sham operated; III (n = 22), bile duct ligation (BDL); IV (n = 21), BDL and GH treatment; and V (n = 20), BDL and IGF-I administration. By the end of the experiment, on day 10, blood bilirubin was determined, and mesenteric lymph nodes, liver specimens, and bile from the bile duct stump were cultured. Endotoxin was measured in portal and aortic blood. Tissue samples from the terminal ileum and liver were examined histologically and apoptotic body count (ABC) in intestinal mucosa was evaluated. Mucosal DNA and protein content were also determined. RESULTS: Bilirubin increased significantly after BDL (p < 0.001). Bile from the bile duct was sterile. In group III, MLN and liver specimens were contaminated by gut origin bacteria (significant versus group I and II, p < 0.001, respectively). GH reduced significantly positive cultures (p < 0.01), and IGF-I had no effect. BDL resulted in significant increase in portal and aortic endotoxemia (p < 0.001); treatment with GH and IGF-I reduced it (p < 0.001). Mucosal DNA and protein content were reduced in animals with BDL and after treatment with GH or IGF-I; an increase to almost normal levels was noted in DNA, but not in protein. Overall the ileal architecture remained intact in all animal groups. The ABC increased after BDL. After GH and IGF-I administration, the ABC decreased significantly, and there was no difference between GH and IGF-I treated animals. After BDL, liver biopsies displayed typical changes of biliary obstruction, which were significantly improved after administration of GH and IGF-I. CONCLUSIONS: Treatment with GH and IGF-I in rats with experimental obstructive jaundice reduces endotoxemia, and it improves liver histology. Apoptosis, in the intestinal epithelium, may serve as a morphologic marker of the ileal mucosal integrity, demonstrating the proliferative potential of GH and IGF-I in cases of obstructive jaundice, and this might be of potential value in patients with such conditions.     

Attenuation of Kupffer Cell Function in Acute on Chronic Liver Injury Enhanced Engraftment of Transplanted Hepatocytes

Background The present study was designed to elucidate the relationship of engraftment efficiency of transplanted cells and Kupffer cell function in mice with acute on chronic liver injury and acute liver injury. Methods The recipient dipeptidyl peptidase IV knockout (DPPIV^–/–) mice were divided into two groups: (1) the acute on chronic liver injury group (CCl₄/APAP group) that received CCl₄ (1 ml/kg) twice a week for 4 weeks following one dose of acetaminophen (APAP), 600 mg/kg; (2) the acute liver injury group (APAP-only group) that received a single dose of APAP at 600 mg/kg. DPPIV^+/+ hepatocytes were transplanted 24 h after APAP intoxication. Engraftment efficiency was evaluated at day 7 and day 14 after transplantation. The tumor necrosis factor-α (TNF-α) mRNA expression level of Kupffer cells immediately before cell transplantation was compared between the two groups before and after lipopolysaccharide (LPS, 100 ng/ml) stimulation. Results The number of transplanted cells and clusters in each 100× microscopic field were higher in the CCl₄/APAP group at both day 7 (21.5 ± 6.3 versus 8.3 ± 4.0, p < 0.001; 14.9 ± 4.6 versus 6.6 ± 3.4, p < 0.001, respectively) and day 14 (17.3 ± 4.4 versus 10.2 ± 3.3, p = 0.001; 12.6 ± 3.2 versus 7.9 ± 1.6, p = 0.004, respectively). After LPS stimulation, the expression level of TNF-α was lower (175.7 ± 54.6 versus 465.6 ± 64.2, p = 0.002), and the increment of TNF-α expression was also less significant in the CCl₄/APAP group (1.5-fold versus 6.5-fold, p = 0.014). Conclusions Chronic liver injury desensitized Kupffer cells and reduced TNF-α expression, two results that correlated with the increased engraftment of transplanted cells.     

Effects of biliary drainage in obstructive jaundice on microcirculation,phagocytic activity,and ultrastructure of the liver in rats

Background/Purpose: Biliary drainage before surgery for obstructive jaundice has been thought to be indispensable, because these patients tend to develop various complications after the surgery. We developed jaundiced rat models, and studied the effects of biliary drainage on the hepatic blood flow rate, portal pressure, and phagocytic activity. Methods: We generated rats with obstructive jaundice by surgical ligation followed by cutting of the common bile duct; some jaundiced rats then underwent biliary drainage. Lipopolysaccharide (LPS) was intraperitoneally administered to some rats. Control rats underwent open abdominal surgery alone. Ultrastructural changes of the liver sinusoidal endothelial cells were examined by scanning electron microscopy. Results: The hepatic blood flow rate and phagocytic activity in the jaundiced rats and the LPS-treated jaundiced rats were lower than those in the control rats. Biliary drainage improved the hepatic blood flow rate in both the jaundiced rats and the LPS-treated jaundiced rats to the control levels. Scanning electron microscopic observation of the liver sinusoids showed that, in the jaundiced rats, the endothelial cells were hypertrophic and there was a reduced number of fenestrae. In jaundiced rats that underwent biliary drainage, the hypertrophy was reduced, and the number of fenestrae was increased in comparison with those in the jaundiced rats without the drainage. Conclusions: These findings indicate that biliary drainage was effective in jaundiced and LPS-treated jaundiced rats. Received: November 16, 2001 / Accepted: February 11, 2002