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

Abstract

Bacterial translocation appears to be an important mechanism in the pathogenesis of spontaneous infections in cirrhosis. Cirrhotic patients are commonly treated with ␤-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 intesti- Cirrhotic patients are prone to bacterial infections, with spontaneous bacterial peritonitis (SBP) being the most characteristic. Clinical and experimental evidence indicates that translocation of bacteria from the intestinal lumen to the bloodstream is directly involved in the pathogenesis of these spontaneous infections. SBP is caused predominantly by enteric organisms, 1 and selective intestinal decontamination lowers the rate of first or recurrent SBP in cirrhotic patients. 2 Studies in carbon tetrachloride (CCl 4 )-induced cirrhotic rats have shown the frequent, simultaneous presence of bacterial translocation (BT) and SBP caused by enteric organisms, 3-5 a higher rate of BT in ascitic than in nonascitic animals, 6 frequent genotype identity between ileal flora and bacteria colonizing the mesenteric lymph nodes (MLN), 7 and a reduction, by selective intestinal decontamination, in the incidence of BT after hemorrhagic shock. 8 The factors that favor BT in cirrhosis are incompletely understood. Proposed mechanisms include disruption of the equilibrium of normal intestinal bacterial flora, increased permeability of the intestinal mucosal barrier, and deficiencies in host immune def...

Oral Bile Acids Reduce Bacterial Overgrowth, Bacterial Translocation, and Endotoxemia in Cirrhotic Rats

“…42,43 Recent studies have shown that bacterial overgrowth and bacterial translocation can also be decreased in experimental cirrhosis by accelerating intestinal transit with cisapride 14 or with propranolol. 44 However, cisapride can produce QT interval prolongation and ventricular arrhythmias. 45 Propranolol cannot be used in all cirrhotic patients and is also known to sometimes have severe adverse effects in cirrhotic patients.…”

Peripheral Blood Mononuclear Cell Expression of Toll–Like Receptors and Relation to Cytokine Levels in Cirrhosis

“…[24][25][26] Increased extraintestinal translocation of Gram-positive bacterial antigens would be expected in such circumstances, given experiences in experimental animals. 43,44 Indeed, lipoteichoic acid, a component of Gram-positive bacteria, has recently been found in liver tissue of cirrhotic patients, presumably as a consequence of extraintestinal translocation from the gut lumen. 27 We found evidence that Gram-positive gut flora may influence systemic TLR expression, serum TNF-␣ levels, and in vitro TNF-␣ production in cirrhotic patients.…”

Bloodstream infections in patients with liver cirrhosis

“…[27][28][29] In animal models of LC, portal hypertension and intestinal hypo-mobility lead to bacterial overgrowth in the small bowel and is considered the primum movens of translocation in these models. 30 In a clinical study of 24 patients with liver cirrhosis the bacterial overgrowth was enhanced by portal hypertension, as suggested by animal models. 31 In addition progressive intestinal dysbiosis was identified in patients with LC especially in advanced stages of the disease.…”