Cirrhotic rats with bacterial translocation have higher incidence and severity of hepatopulmonary syndrome.
BACKGROUND
Bacterial translocation, that is, extra-intestinal dissemination of gut bacteria, occurs in approximately 50% of humans and rats with cirrhosis and plays a significant role in enhanced tumor necrosis factor-alpha (TNF-alpha) production. The authors' previous studies have indicated that prevention of bacterial translocation with norfloxacine or inhibition of TNF-alpha with pentoxifylline treatment decreased both the incidence and severity of hepatopulmonary syndrome by attenuating the induction of pulmonary intravascular macrophages in cirrhotic rats. In the present study the hypothesis was tested that the cirrhotic rats with bacterial translocation had higher TNF-alpha production, higher level of sequestration of macrophages in pulmonary vessels, and increased incidence and severity of hepatopulmonary syndrome.


METHODS
Rats were studied 5 weeks after common bile duct ligation or sham operation. Bacterial translocation was defined by positive mesenteric lymph node cultures. Hepatopulmonary syndrome was assessed by measurements of alveoloarterial oxygen difference (AaPO(2)) and intrapulmonary shunt. The TNF-alpha concentration in plasma was measured by ELISA. Pulmonary intravascular macrophage sequestration was assessed by lung morphometric analysis.


RESULTS
Bacterial translocation occurred in 48% of cirrhotic rats. Plasma concentrations of TNF-alpha and the percentage of vessels with pulmonary intravascular macrophages were higher in the cirrhotic rats with bacterial translocation. Rats with bacterial translocation also had a higher incidence (9% vs 63%, P < 0.01) and severity of hepatopulmonary syndrome, as indicated by higher levels of both AaPO(2) and intrapulmonary shunt.


CONCLUSIONS
These results suggest that bacterial translocation may play a role in the pathogenesis of hepatopulmonary syndrome by inducing pulmonary intravascular macrophages through TNF-alpha upregulation.
Sztrymf
Benjamin
B
Surgical Laboratory-UPRES (EA-2705), Marie Lannelongue Surgical Center, Paris-South University, Le Plessis Robinson, France.
Libert
Jean-Marie
JM
Mougeot
Christine
C
Lebrec
Didier
D
Mazmanian
Michel
M
Humbert
Marc
M
Herve
Philippe
P
D000818:Animals; D001158:Arteries; D018988:Bacterial Translocation; D001808:Blood Vessels / Q000473:pathology; D020065:Hepatopulmonary Syndrome / Q000453:epidemiology* / Q000209:etiology / Q000503:physiopathology*; D015994:Incidence; D008103:Liver Cirrhosis / Q000150:complications* / Q000382:microbiology*; D008168:Lung / Q000098:blood supply; D008264:Macrophages / Q000473:pathology; D008297:Male; D009994:Osmolar Concentration; D010100:Oxygen / Q000097:blood / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D010100:Oxygen