Prevention of Gram-Negative Translocation Reduces the Severity of Hepatopulmonary Syndrome

• Published in: American journal of respiratory and critical care medicine Vol. 166; no. 4; pp. 514 - 517
• Main Authors: Rabiller, Anne, Nunes, Hilario, Lebrec, Didier, Tazi, Khalid A, Wartski, Myriam, Dulmet, Elisabeth, Libert, Jean-Marie, Mougeot, Christine, Moreau, Richard, Mazmanian, Michel, Humbert, Marc, Herve, Philippe
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 15.08.2002; American Lung Association
• Subjects: Animals; Anti-Infective Agents - therapeutic use; Antibiotic Prophylaxis - methods; Antibiotic Prophylaxis - standards; Bacterial Translocation; Biological and medical sciences; Common Bile Duct - surgery; Disease Models, Animal; Drug Evaluation, Preclinical; Gram-Negative Bacteria - physiology; Gram-Negative Bacterial Infections - complications; Gram-Negative Bacterial Infections - prevention & control; Hemodynamics; Hepatopulmonary Syndrome - metabolism; Hepatopulmonary Syndrome - microbiology; Hepatopulmonary Syndrome - physiopathology; Ligation; Liver Cirrhosis - complications; Macrophages, Alveolar - chemistry; Macrophages, Alveolar - physiology; Male; Medical sciences; Nitric Oxide - analysis; Nitric Oxide - physiology; Nitric Oxide Synthase - analysis; Nitric Oxide Synthase - physiology; Nitric Oxide Synthase Type II; Norfloxacin - therapeutic use; Pneumology; Pulmonary Circulation; Rats; Rats, Wistar; Respiratory system : syndromes and miscellaneous diseases; Severity of Illness Index; Translocation; Lung disease; Rat; Respiratory disease; Enzyme; Pathogenesis; Rodentia; Clinical form; Hepatic disease; Nitric-oxide synthase; Infection; Cirrhosis; Vertebrata; Mammalia; Animal; Bacteriosis; Digestive diseases; Bacteria; Oxidoreductases; Pneumopathy; Macrophage
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200201-027OC

Hepatopulmonary syndrome (HPS) is characterized by intrapulmonary vascular dilatations and an increased alveoloarterial oxygen difference (AaPO(2)). These abnormalities are related to augmented pulmonary nitric oxide (NO) production, dependent primarily on increases in the expression and activity of inducible NO-synthase (iNOS) within pulmonary intravascular macrophages and, to a lesser extent, of endothelial NOS (eNOS). Production of iNOS by pulmonary intravascular macrophages might be related to translocated gut bacteria present in the pulmonary circulation. To test this hypothesis, we determined whether macrophage sequestration, lung iNOS expression and activity, and HPS severity were decreased after norfloxacin was given for 5 weeks to prevent Gram-negative bacterial translocation in rats with common bile duct ligation-induced cirrhosis. Norfloxacin decreased the incidence of Gram-negative translocation from 70 to 0% and the percentage of pulmonary microvessels containing more than 10 macrophages from 52 +/- 7 to 21 +/- 8% (p < 0.01). AaPO(2) and cerebral uptake of intravenous (99m)Tc-labeled albumin macroaggregates (reflecting intrapulmonary vascular dilatations) were intermediate to those of untreated cirrhotic and sham-operated rats. The activity and expression of lung iNOS, but not eNOS, were reduced to normal. Norfloxacin may reduce HPS severity by inhibiting Gram-negative bacterial translocation, thereby decreasing NO production by pulmonary intravascular macrophages. Bacterial translocation may be the key to the pathogenesis of HPS.