Bacterial translocation in cirrhotic rats. Its role in the development of spontaneous bacterial peritonitis.

Bacterial translocation occurs in ascitic cirrhotic rats, but its association with ascites infection is unknown. The aim of this study was to assess the relation between bacterial translocation and ascites infection in cirrhotic rats. Male Sprague-Dawley rats were induced to cirrhosis with intragastric CCl4. Ascitic fluid, portal and peripheral blood, mesenteric lymph nodes, liver and spleen samples were cultured before death in those cirrhotic rats with less (group A) or more (group B) than 250 polymorphonuclear neutrophils/mm3 in ascitic fluid, as well as in healthy control rats. Histological examination of jejunum, ileum, and caecum was also performed. Bacterial translocation occurred in 45% of ascitic rats (without differences between groups A and B), but in 0% controls (p = 0.01). Bacterial translocation was associated with positive ascitic fluid culture in 60% of the cases. In all of them the same bacterial species was isolated in both mesenteric lymph node and ascitic fluid. Submucosal caecal oedema (100%), ileal lymphangiectasia (41%), and caecal inflammatory infiltrate (41%) occurred in ascitic rats, the last being associated with ascitic fluid positive culture (p = 0.04). These results suggests that bacterial translocation occurs frequently in ascitic cirrhotic rats, and may play a permissive, but not unique, part in a number of ascites infections. Whether histological changes seen in cirrhotic ascitic rats favour bacterial translocation remains to be elucidated.     

Allopurinol and glutamine attenuate bacterial translocation in chronic portal hypertensive and common bile duct ligated growing rats.

BACKGROUND: Spontaneous bacterial infections and septicaemia result in morbidity and mortality in patients with portal hypertension and obstructive jaundice. AIM: The aim of this study in rats was to investigate the incidence of bacterial translocation in portal hypertension and obstructive jaundice, and to evaluate the effects of allopurinol and glutamine. METHODS: Rats were subjected to sham laparotomy (SL), portal hypertension (PH) by calibrated stenosis of the portal vein, and common bile duct ligation (CBDL). Animals of each group were either treated with allopurinol (50 mg/kg twice a week), glutamine (1 g/kg/d), and allopurinol and glutamine. RESULTS: After four weeks, significant bacterial translocation in the untreated PH and CBDL rats occurred. Intestinal mucosal malondialdehyde concentrations (MDA), as an indicator for lipid peroxidation, and myeloperoxidase activity (MPO) released from activated neutrophils were also significantly increased (p < 0.01). Allopurinol and glutamine in PH and CBDL rats improved bacterial translocation, and decreased MDA and MPO values (p < 0.01). CONCLUSION: In PH and CBDL rats significant bacterial translocation, ileal mucosal lipid peroxidation, and neutrophil derived MPO activity occurred. Allopurinol and glutamine significantly reduced bacterial translocation, as well as ileal mucosal MDA and MPO activities.     

Effect of Lactobacillus johnsonii La1 and antioxidants on intestinal flora and bacterial translocation in rats with experimental cirrhosis

BACKGROUND/AIMS: Probiotics and antioxidants could be alternatives to antibiotics in the prevention of bacterial infections in cirrhosis. The aim of the present study was to determine the effect of Lactobacillus johnsonii La1 and antioxidants on intestinal flora, endotoxemia, and bacterial translocation in cirrhotic rats. METHODS: Twenty-nine Sprague-Dawley rats with cirrhosis induced by CCl(4) and ascites received Lactobacillus johnsonii La1 10(9)cfu/day in vehicle (antioxidants: vitamin C+glutamate) (n=10), vehicle alone (n=11), or water (n=8) by gavage. Another eight non-cirrhotic rats formed the control group. After 10 days of treatment, a laparotomy was performed to determine microbiological study of ileal and cecal feces, bacterial translocation, endotoxemia, and intestinal malondialdehyde (MDA) levels as index of intestinal oxidative damage. RESULTS: Intestinal enterobacteria and enterococci, bacterial translocation (0/11 and 0/10 vs. 5/8, P<0.01), and ileal MDA levels (P<0.01) were lower in cirrhotic rats treated with antioxidants alone or in combination with Lactobacillus johnsonii La1 compared to cirrhotic rats receiving water. Only rats treated with antioxidants and Lactobacillus johnsonii La1 showed a decrease in endotoxemia with respect to cirrhotic rats receiving water (P<0.05). CONCLUSIONS: Antioxidants alone or in combination with Lactobacillus johnsonii La1 can be useful in preventing bacterial translocation in cirrhosis.     

Intestinal permeability in rats with CCl4-induced portal hypertension

AIM: To investigate the intestinal barrier changes in rats with CCl4-induced portal hypertension. METHODS: The permeability of intestinal barrier detected by Lanthanum as a tracer was evaluated in rats. Bacterial translocation and plasma endotoxin were also determined. RESULTS: The incidence of bacterial translocation was 85% in rats with CCl4-induced portal hypertension, which was significantly higher than that in control rats (20%, P<0.01). Plasma endotoxin level was significantly higher in experimental group than in control group. Permeability of the epithelial mucosa and pathological alteration were increased in the ileum and the microvilli became shorter and thinner in rats with portal hypertension. CONCLUSION: Bacterial translocation occurs in rats with CCl4-induced portal hypertension and increased permeability between epithelial cells contributes to the translocation.     

Intestinal ischemia-reperfusion injury augments intestinal mucosal injury and bacterial translocation in jaundiced rats

BACKGROUND/AIMS: The aim of this study was to evaluate local effects and degree of bacterial translocation related with intestinal ischemia-reperfusion injury in a rat obstructive jaundice model. METHODOLOGY: Thirty adult Sprague-Dawley rats (200-250 g) were divided into three groups; including Group 1 (jaundice group), Group 2 (jaundice-ischemia group) and Group 3 (ischemia group). All rats had 2 laparotomies. After experimental interventions, tissue samples for translocation; liver and ileum samples for histopathological examination, 25 cm of small intestine for mucosal myeloperoxidase and malondialdehyde levels and blood samples for biochemical analysis were obtained. RESULTS: Jaundiced rats had increased liver enzyme levels and total and direct bilirubin levels (p<0.05). Intestinal mucosal myeloperoxidase and malondialdehyde levels were found to be high in intestinal ischemia-reperfusion groups (p<0.05). Intestinal mucosal damage was more severe in rats with intestinal ischemia-reperfusion after bile duct ligation (p<0.05). Degree of bacterial translocation was also found to be significantly high in these rats (p<0.05). CONCLUSIONS: Intestinal mucosa is disturbed more severely in obstructive jaundice with the development of ischemia and reperfusion. Development of intestinal ischemia-reperfusion in obstructive jaundice increases bacterial translocation.     

Effect of propranolol on the factors promoting bacterial translocation in cirrhotic rats with ascites

Bacterial translocation appears to be an important mechanism in the pathogenesis of spontaneous infections in cirrhosis. Cirrhotic patients are commonly treated with beta-adrenoceptor blockers, but the impact of this treatment in the factors promoting bacterial translocation has not been investigated. This study was aimed at investigating in cirrhotic rats with ascites the effect of propranolol on intestinal bacterial load, transit, and permeability of the bowel and on the rate of bacterial translocation. Bacterial translocation to mesenteric lymph nodes and intestinal bacterial overgrowth, permeability (urinary excretion of (99m)Tc-diethylenetriaminepentaacetic acid [(99m)Tc-DTPA]), and transit (geometric center ratio of (51)Cr) were assessed in 29 rats with carbon tetrachloride (CCl(4)) cirrhosis and 20 controls. These variables were then measured in 12 placebo- and in 13 propranolol-treated ascitic cirrhotic rats. Bacterial translocation was present in 48% of the cirrhotic rats and in none of the controls. Cirrhotic rats with intestinal bacterial overgrowth had a significantly higher rate of translocation and slower intestinal transit than those without it. Among the 15 rats with overgrowth and a (99m)Tc-DTPA excretion greater than 10%, 15 had translocation and 2 had bacterial peritonitis. Only 1 of the 14 rats with either intestinal overgrowth or a (99m)Tc-DTPA excretion greater than 10% presented translocation. Compared with the placebo group, propranolol-treated animals had significantly lower portal pressure, faster intestinal transit, and lower rates of bacterial overgrowth and translocation. In ascitic cirrhotic rats, bacterial translocation results from intestinal overgrowth and severe damage to gut permeability. In this setting, intestinal overgrowth is associated with intestinal hypomotility. Propranolol accelerates the intestinal transit, decreasing the rates of bacterial overgrowth and translocation.     

Intestinal permeability in rats with CCI4-induced portal hypertension

AIM:To investigate the intestinal barrier changes in ratswith CCl_4-induced portal hypertension.METHODS:The permeability of intestinal barrier detectedby Lanthanum as a tracer was evaluated in rats,Bacterialtranslocation and plasma endotoxin were also determined.RESULTS:The incidence of bacterial translocation was85% in rats with CCl_4-induced portal hypertension,whichwas significantly higher than that in control rats(20%,P<0.01).Plasma endotoxin level was significantly higherin experimental group than in control group.Permeabilityof the epithelial mucosa and pathological alteration wereincreased in the ileum and the microvilli became shorterand thinner in rats with portal hypertension.CONCLUSION:Bacterial translocation occurs in ratswith CCl_4-induced portal hypertension and increasedpermeability between epithelial cells contributes to thetranslocation.     

Intestinal permeability in rats with CCl4-induced portal hypertension

AIM: To investigate the intestinal barrier changes in rats with CCl4-induced portal hypertension.METHODS: The permeability of intestinal barrier detected by Lanthanum as a tracer was evaluated in rats. Bacterial translocation and plasma endotoxin were also determined.RESULTS: The incidence of bacterial translocation was 85% in rats with CCl4-induced portal hypertension, which was significantly higher than that in control rats (20%,P＜0.01). Plasma endotoxin level was significantly higher in experimental group than in control group. Permeability of the epithelial mucosa and pathological alteration were increased in the ileum and the microvilli became shorter and thinner in rats with portal hypertension.CONCLUSION: Bacterial translocation occurs in rats with CCl4-induced portal hypertension and increased permeability between epithelial cells contributes to the translocation.     

Role of intestinal bacterial overgrowth and intestinal motility in bacterial translocation in experimental cirrhosis.

BACKGROUND: Intestinal bacterial overgrowth (IBO) is related to small bowel motility and has been involved in the pathogenesis of bacterial translocation (BT) in experimental models, and both overgrowing gut flora and translocating bacteria to mesenteric lymph nodes are common features in cirrhosis. OBJECTIVES: The aims of this study were to analyze cecal aerobic bacteria and intestinal transit in cirrhotic rats, and their relationship with BT, evaluating the role of intestinal bacterial overgrowth and small bowel dismotility in the development of BT in experimental cirrhosis. MATERIAL AND METHODS: We included twenty-seven male Sprague-Dawley rats with carbon tetrachloride-induced cirrhosis without ascites and ten controls. Cultures of mesenteric lymph nodes (MLN), peripheral and portal blood, liver, spleen and cecal samples were carried out. Small intestinal transit was determined in ten cirrhotic rats and in ten control rats. RESULTS: The prevalence of bacterial translocation was 56%. Total cecal aerobic bacteria count was significantly higher in cirrhotic rats than in control rats (p < 0.001). Cirrhotic rats with translocated bacteria had higher total aerobic intestinal counts than culture-negative MLN bacteria (p < 0.05). The prevalence of total intestinal bacterial overgrowth in cirrhotic animals was 67%, and 0% in control animals (p < 0.001). According to BT, total IBO was more frequent in cirrhotic rats with BT versus those without BT (93 vs. 33%) (p < 0.001). Of the translocating bacteria, 95.6% were found to be overgrown in the cecum. The small-intestinal transit was slower in cirrhotic rats (60.5 +/- 12.7 cm vs. 81.2 +/- 5.7 cm) than in control animals (p < 0.001). CONCLUSIONS: These results suggest that the increase of intestinal aerobic bacteria in experimental cirrhosis is associated with translocation. In addition, IBO is frequent in cirrhotic rats, and is supposed to play an important role in the development of BT. Impaired motility of the small intestine is a common feature in cirrhosis and may be implicated in the pathogenesis of IBO.     

Oral bile acids reduce bacterial overgrowth,bacterial translocation,and endotoxemia in cirrhotic rats

Experiments were performed to test whether conjugated bile acid administration would decrease bacterial overgrowth, bacterial translocation, and endotoxemia in ascitic cirrhotic rats. Cholylsarcosine, a deconjugation-dehydroxylation resistant and cholylglycine, a deconjugation-dehydroxylation susceptible bile acid were used. Rats with CCl(4)-induced cirrhosis and ascites were fed cholylsarcosine, cholylglycine (both at 70 mg/kg/d), or placebo for 2 weeks. Healthy rats, as controls, were treated similarly. In cirrhotic rats receiving placebo, bile secretion from an acute biliary fistula was lower than in healthy rats (27.2 +/- 6.5 vs. 53.0 +/- 3.1 microL/kg/min; mean +/- SE, P<.05). The administration of conjugated bile acids to cirrhotic rats normalized bile secretion (cholylsarcosine, 51.8 +/- 6.29; cholylglycine, 52.72 +/- 8.9 microL/kg/min). Total ileal bacterial content was 6-fold higher in ascitic cirrhotic rats than in healthy rats. Conjugated bile acid administration reduced bacterial content to normal levels. Bacterial translocation was less in cirrhotic animals receiving conjugated bile acids (cholylsarcosine, 33%; cholylglycine, 26%) than in animals receiving placebo (66%). Endotoxemia was decreased in cirrhotic rats by conjugated bile acid feeding (cholylsarcosine, 0.098 +/- 0.002; cholylglycine 0.101 +/- 0.007 EU/mL) compared with placebo (0.282 +/- 0.124, P <.001). Survival was greater in animals receiving conjugated bile acids (cholylsarcosine, 10/15; cholylglycine, 11/15; placebo, 5/15). In conclusion, the administration of conjugated bile acids to ascitic cirrhotic rats increased bile acid secretion, eliminated intestinal bacterial overgrowth, decreased bacterial translocation, decreased endotoxemia, and increased survival. Oral conjugated bile acids may be useful in preventing bacterial translocation, endotoxemia, and spontaneous bacterial perotonitis in cirrhotic patients.     

Ginkgo biloba extract prevents mucosal damage associated with small-intestinal ischaemia

We have examined how a Ginkgo biloba extract influences the damaging effects of ischaemia in the small-intestinal mucosa. We used a rat experimental model in which a ligated loop of the distal ileum was subjected to ischaemia and revascularization, and the ensuing mucosal damage assessed by lysosomal enzyme release and intestinal permeability measurements. We also determined the mucosal content of malondialdehyde, a lipid peroxidation product, and the mucosal activity of myeloperoxidase, a neutrophil granulocyte marker. Ischaemia and revascularization alone caused increased mucosal permeability to sodium fluorescein, increased N-acetyl-beta-glucosaminidase release from the mucosa into the lumen, increased malondialdehyde content in the mucosa, and increased myeloperoxidase activity in the mucosa. Intravenous injection of G. biloba extract caused a dose-dependent attenuation of all these effects of ischaemia. It is suggested, therefore, that G. biloba extract may protect the intestinal mucosa against ischaemic damage by reducing neutrophil infiltration and lipid peroxidation.     

Intestinal bacterial overgrowth and bacterial translocation in cirrhotic rats with ascites

Background/Aims: Translocation of indigenous bacterial from the gut lumen of cirrhotic animals to mesenteric lymph nodes appears to be an important step in the pathogenesis of spontaneous bacterial peritonitis. However, the sequence of events leading to translocation remains unclear. One of the most predictable risk factors for translocation is overgrowth of gut bacterial flora. The present study was designed to compare the intestinal aerobic bacterial flora of cecal stools at the time of sacrifice between cirrhotic and normal rats and to evaluate the role of intestinal aerobic bacterial overgrowth in bacterial translocation in cirrhotic rats.Methods: Thirty-five male Sprague-Dawley rats with carbon tetrachloride-induced cirrhosis and ascites and 10 normal rats were included in this study. Cirrhotic rats were sacrificed when ill and samples of ascitic fluid, mesenteric lymph nodes and cecal stool were taken for detecting quantitatively aerobic bacteria.Results: Total intestinal aerobic bacterial count in cecal stool at the time of sacrifice was significantly increased in cirrhotic rats with bacterial translocation with or without spontaneous bacterial peritonitis compared to cirrhotic rats without bacterial translocation (p<0.001 and p<0.001, respectively) and to normal rats (p<0.001 and p<0.001, respectively). Of the 42 species of bacteria translocating to the mesenteric lymph nodes, 41 (97.6%) were found in supranormal numbers in the stool at the time of sacrifice.Conclusions: Carbon tetrachloride-induced cirrhotic rats with bacterial translocation have increased total intestinal aerobic bacteria count, and intestinal bacterial overgrowth appears to play an important role in bacterial translocation in this experimental model of cirrhosis in rats.     

Pathogenesis of postantibiotic diarrhoea caused by Clostridium difficile: an in vitro study in the rabbit intestine.

To elucidate the pathophysiological changes leading to postantibiotic diarrhoea caused by Clostridium difficile and its cytotoxin, oral ampicillin was given to rabbits, and jejunal, ileal, and caecal segments of those that developed diarrhoea were investigated in vitro. The rabbits that, in response to treatment, harboured Clostridium difficile in their colonic lumen were studied, and the results expressed according to the presence or absence of Clostridium difficile and/or its cytotoxin. Thus, we refer to either CD+ or CD- segments. The influx of glucose, phenylalanine, glycylphenylalanine, and lysine across the brush border of jejunum and ileum of CD+ segments was severely impaired, while only slightly blunted in CD-. No significant change was detected in the influx of glutamic acid in the jejunum of all treated animals and in the CD- ilea. Morphologic damage in ileum and caecum of CD+ was also more evident than in CD-. Transepithelial ion transport across short circuited ileal mucosa (CD+ and CD-) revealed secretory changes in Cl net transport that were more marked in CD-. We conclude that: (1) Clostridium difficile may also colonise the upper intestinal tract, where it induces morphological and functional damage, severely impairing nutrient absorption; and (2) the ileum contributes to the diarrhoea caused by CD even when the micro-organism is confined to the more distal gut by showing moderate impairment of nutrient absorption and marked electrolyte secretion.     

Insulin-like growth factor I improves intestinal barrier function in cirrhotic rats

BACKGROUND AND AIMS: In liver cirrhosis, disruption of the intestinal barrier facilitates bacterial translocation and spontaneous bacterial peritonitis. Insulin-like growth factor I (IGF-I) is an anabolic hormone synthesised by hepatocytes that displays hepatoprotective activities and trophic effects on the intestine. The aim of this study was to investigate the effect of IGF-I on intestinal barrier function in cirrhotic rats. METHODS: In rats with carbon tetrachloride induced cirrhosis, we investigated the effect of IGF-I therapy on: (a) portal pressure; (b) intestinal histology and permeability to endotoxin and bacteria; (c) intestinal expression of cyclooxygenase 2 (COX-2) and tumour necrosis factor alpha (TNF-alpha), two factors that influence in a positive and negative manner, respectively, the integrity of the intestinal barrier; (d) intestinal permeability to 3H-mannitol in rats with bile duct ligation (BDL); and (e) transepithelial electrical resistance (TER) of polarised monolayers of rat small intestine epithelial cells. RESULTS: IGF-I therapy reduced liver collagen expression and portal pressure in cirrhotic rats, induced improvement in intestinal histology, and caused a reduction in bacterial translocation and endotoxaemia. These changes were associated with diminished TNF-alpha expression and elevated COX-2 levels in the intestine. IGF-I reduced intestinal permeability in BDL rats and enhanced barrier function of the monolayers of epithelial intestinal cells where lipopolysaccharide (LPS) caused a decrease in TER that was reversed by IGF-I. This effect of IGF-I was associated with upregulation of COX-2 in LPS treated enterocytes. CONCLUSIONS: IGF-I enhances intestinal barrier function and reduces endotoxaemia and bacterial translocation in cirrhotic rats. IGF-I therapy might be useful in the prevention of spontaneous bacterial peritonitis in liver cirrhosis.     

Reduction of intestinal apo A-IV mRNA levels in the cirrhotic rat

In the present study, intestinal apo A-IV synthesis was investigated using a carbon tetrachloride (CCl₄)-induced cirrhosis rat model. Triglyceride (TG) content in rat cirrhotic liver was increased markedly by 170% (P< 0.001) and apo B was increased by 20% (P<0.05) compared with control levels. These results reflected the steatotic change in the liver. In contrast, TG levels in the small intestine of cirrhotic rats decreased significantly (P<0.01). In addition, intestinal apo A-IV (jejunum P< 0.001; ileum P< 0.01) and its mRNA levels (jejunum P< 0.01; ileum P< 0.05) were also reduced. The decreased apo A-IV content in the jejunum was confirmed by immunohistochemical analysis. These results indicate that intestinal apo A-IV synthesis in cirrhosis is suppressed, at least under the condition of an overnight fast. Therefore, decreased intestinal apo A-IV synthesis may relate to the decreased ability to absorb fat in cirrhosis, but a fat-loading study will be necessary to confirm this hypothesis. It is unknown from the present study why serum apo A-IV level is not significantly decreased, despite a reduction in apo A-IV synthesis. The clearance of apo A-IV by the liver may be delayed or apo A-IV synthesis may be rather markedly enhanced during fat absorption in liver cirrhosis.     

Effect of cisapride on intestinal bacterial and endotoxin translocation in cirrhosis

AIM: To investigate the effects of cisapride on intestinal bacterial overgrowth (IBO), bacterial and endotoxin translocation, intestinal transit and permeability in cirrhotic rats. METHODS: All animals were assessed with variables including bacterial and endotoxin translocation, intestinal bacterial overgrowth, intestinal transit and permeability. Bacterial translocation (BT) was assessed by bacterial culture of MLN, liver and spleen, IBO by a jejunal bacterial count of the specific organism, intestinal permeability by determination of the 24-hour urinary (99m)Tc-DTPA excretion and intestinal transit by measurement of the distribution of (51)Cr in the intestine. RESULTS: Bacterial translocation (BT) and IBO was found in 48 % and 80 % cirrhotic rats respectively and none in control rats. Urinary excretion of (99m)Tc-DTPA in cirrhotic rats with BT (22.2+/-7.8) was greater than these without BT (10.5+/-2.9). Intestinal transit (geometric center ratio) was significantly delayed in cirrhotic rats (0.31+/-0.06) and further more delayed in cirrhotic rats with BT (0.24+/-0.06) than these without BT (0.38+/-0.11). Cirrhotic rats with IBO had significantly higher rates of intestinal bacterial and endotoxin translocation, slower intestinal transit time and higher intestinal permeability than those without IBO. It was also found that BT was closely associated with IBO and the injury of intestinal barrier. Compared with the placebo group, cisapride-treated rats had lower rates of bacterial/endotoxin translocation and IBO, which was closely associated with increased intestinal transit and improved intestinal permeability by cisapride. CONCLUSION: These results indicate that endotoxin and bacterial translocation in cirrhotic rats may be attributed to IBO and increased intestinal permeability. Cisapride that accelerates intestinal transit and improve intestinal permeability might be helpful in preventing intestinal bacterial and endotoxin translocation.     

急性肝衰竭大鼠肠道菌群和内毒素的动态研究

目的 研究急性肝衰竭大鼠肠道菌群及内毒素的动态变化。 方法 腹腔注射半乳糖胺建立急性肝衰竭大鼠模型。40只SD大鼠随机分为A组(对照组)10只;B组12只,C组18只(均为肝衰竭大鼠)。实验开始时(A组)、造模后24 h(B组)和48 h(C组)分别处死各组大鼠并检测肝功能,定性、定量分析空肠、回肠及结肠菌群,定量测定门静脉、右心室血,回肠及结肠内毒素。 结果 肝功能检测显示:B组大鼠的肝脏损伤最为严重;与B组相比,C组大鼠的肝功能开始好转。肠道菌群分析显示:B组大鼠肠道内肠杆菌科细菌显著增加(空肠、回肠间,P<0.01;结肠间,P<0.05)、乳酸杆菌下降(P<0.01);与B组相比,C组空肠和结肠内的肠杆菌科细菌出现下降(P<0.05)、乳酸杆菌增加,以空肠为显著(P<0.05)。内毒素测定表明B组回肠内毒素增加(P<0.05);C组空肠和回肠内毒素继续增高与对照组差异有显著性(P<0.01);门静脉内内毒素在B组最高,与A、C两组比较差异有显著性(P<0.01)。 结论 急性肝衰竭大鼠肠道存在菌群失调、肠杆菌科细菌过度生长,菌群失调程度与肝损伤程度有关;肠道菌群失调伴有回肠和结肠内内毒素升高;门静脉内毒素的增加与肠道菌群失调有关     

Effect of Long-Term Trimethoprim-Sulfamethoxazole Prophylaxis on Ascites Formation, Bacterial Translocation, Spontaneous Bacterial Peritonitis, and Survival in Cirrhotic Rats

Selective intestinal decontamination withnorfloxacin is useful in preventing spontaneousbacterial peritonitis in cirrhotic patients and also incirrhotic rats. The emergence of norfloxacin-resistantinfections in these patients warrants a search foralternative therapies. The aim of this study was toevaluate the effect of long-termtrimethoprimsulfamethoxazole administration on carbontetrachloride (CCl₄)-induced cirrhosis inrats with specific attention to intestinal flora,bacterial translocation, spontaneous bacterialperitonitis (SBP), and survival. Male Sprague-Dawleyrats received CCl₄ administered weekly bygavage. After eight weeks of CCl₄administration rats were randomly allocated into twogroups. Group I received daily overnighttrimethoprim-sulfamethoxazole diluted in phenobarbital water during follow-up and groupII did not. The rats were killed when gravely ill, anda laparotomy was performed to culture samples of cecalstool, mesenteric lymph nodes, and portal and inferior vena caval blood. There was a trendtoward a reduction in the incidence of bacterialtranslocation (8/17 vs 11/14, respectively) and SBP(5/17 vs 7/14, respectively) in treated rats that werekilled just before death compared to untreated rats.A decrease in the incidence of bacterial translocationcaused by gramnegative bacilli was observed in group I(17.6% vs 78.6% , P < 0.01). The development of ascites was delayed in group I (P < 0.05)and survival was prolonged in group I (P < 0.05),despite a higher CCl₄ dose in this group (P< 0.05). In conclusion, long-term prophylactic trimethoprim-sulfamethoxazole administration inCCl₄-induced cirrhosis in rats delayed thedevelopment of ascites, prolonged survival, and reducedthe incidence of gramnegative bacterial translocation but not of SBP, without increasinggram-positive episodes. These data suggest thattrimethoprim-sulfamethoxazole might be a goodalternative to norfloxacin for preventing gram-negativebacterial translocation.     

Failure of Lactobacillus spp. to prevent bacterial translocation in a rat model of experimental cirrhosis

BACKGROUND/AIMS: Prophylaxis of spontaneous bacterial peritonitis in cirrhotic patients with norfloxacin is associated with emergence of quinolone-resistant Enterobacteriaceae. We investigated whether an alternative strategy with Lactobacillus prevents bacterial translocation and ascitic fluid infection in cirrhotic rats. METHODS: CCl(4)-induced cirrhotic rats with ascites (n=34) were allocated to treatment with oral Lactobacillus strain GG at 1-2 x 10(9) cfu/day for 8-10 days (group LGG) or milk (group MILK). In addition, 20 cirrhotic rats were given a single dose of 15 mg norfloxacin orally and then allocated to Lactobacillus (group NOR-LGG) or milk (group NOR-MILK). Ten healthy rats served as control. After sacrifice the cecal flora were analyzed and the prevalence of bacterial translocation and ascitic fluid infection assessed. RESULTS: Cecal colonization with Lactobacillus was achieved in 90% of treated rats. The prevalence of bacterial translocation to mesenteric lymph nodes was 10% in control rats and 93, 84, 70 and 100% in groups MILK, LGG, NOR-MILK and NOR-LGG, respectively (P>0.1 for comparison of treatment groups), the prevalence of ascitic fluid infection was 60, 32, 40 and 40% (P>0.1). Bacterial translocation of Lactobacillus was observed in 24% of rats treated. CONCLUSION: Lactobacilli fail to prevent bacterial translocation and ascitic fluid infection in experimental cirrhosis in spite of successful intestinal colonization.     

Role of endotoxaemia in hyperdynamic circulation in rats with extrahepatic or intrahepatic portal hypertension

This study investigated the role of endotoxaemia in the development of hyperdynamic circulation observed in rats with extrahepatic (high collateralization) or intrahepatic (low collateralization) portal hypertension. Compared with sham-operated rats, decreased mean arterial pressure and systemic vascular resistance were detected on days 1, 4 and 14 following partial portal vein ligation. By day 1, the cardiac index of portal vein-ligated rats was similar to that of sham-operated rats and progressively increased, thereafter, reaching statistically higher values on days 4 and 14. No differences in plasma endotoxin levels were found between portal vein-ligated and sham-operated rats throughout the observation period. Both carbon tetrachloride-induced cirrhotic rats with and without ascites had a higher cardiac index and lower systemic vascular resistance than those of control rats, and cirrhotic rats with ascites had the lowest systemic vascular resistance. Plasma endotoxin levels were higher in cirrhotic rats with ascites (8.6±2.0 pg/mL; P < 0.01) than those of control rats (2.2±0.3 pg/mL) and cirrhotic rats without ascites (2.4±0.6 pg/mL). These results suggest that factors other than endotoxaemia play a role in the development of hyperdynamic circulation observed in rats with extrahepatic portal hypertension and cirrhotic rats without ascites, but that endotoxaemia may contribute to the maintenance of hyperdynamic circulation found in cirrhotic rats with ascites. The severity of liver disease may be a more important factor than the presence of portosystemic shunting for the development of endotoxaemia in portal hypertensive states.