Splanchnic endotoxin levels in cirrhotic rats induced by carbon tetrachloride.
BACKGROUND
Bacterial translocation (passage of intestinal bacteria to mesenteric lymph nodes) observed in cirrhosis may be a source of endotoxin that can stimulate nitric oxide production and participate in the pathogenesis of hyperdynamic circulation. Currently, there are no published data concerning splanchnic endotoxin levels in cirrhotic rats. This study was designed to determine systemic and portal hemodynamics and to detect endotoxins in the portal and systemic circulation.


METHODS
Liver cirrhosis was induced by carbon tetrachloride intragastric gavage. Systemic and splanchnic endotoxin levels in control rats and cirrhotic rats with or without ascites were measured using a chromogenic Limulus assay. In addition, systemic and portal hemodynamic data were obtained using a thermodilution technique and catheterization.


RESULTS
Cirrhotic rats with ascites had the lowest systemic vascular resistance (2.6 +/- 0.1 mmHg.ml-1.min.100 g body weight, BW) compared with control rats (6.3 +/- 0.3 mmHg.ml-1.min.100 g BW; p < 0.05) and cirrhotic rats without ascites (3.7 +/- 0.3 mmHg.ml-1.min.100 g BW; p < 0.05). Cirrhotic rats with ascites displayed the highest splanchnic levels of endotoxin (10.6 +/- 3.1 pg/ml) compared with cirrhotic rats without ascites (2.0 +/- 0.7 pg/ml; p < 0.05) and control rats (2.0 +/- 0.4 pg/ml; p < 0.05). There was no difference in the splanchnic endotoxin levels between control rats and cirrhotic rats without ascites (p > 0.05). Similar results were observed with systemic endotoxin values (cirrhotic rats with ascites, 10.8 +/- 2.8 pg/ml; cirrhotic rats without ascites, 2.7 +/- 0.6 pg/ml; control rats, 2.5 +/- 0.4 pg/ml; p < 0.05). A significant correlation existed between portal and systemic endotoxin values in cirrhotic rats with or without ascites (r = 0.96, p < 0.001 and r = 0.9, p < 0.05, respectively), whereas this correlation did not exist in control rats (r = 0.5, p > 0.05).


CONCLUSIONS
Cirrhotic rats with ascites had the lowest systemic vascular resistance and the highest splanchnic endotoxin levels when compared with cirrhotic rats without ascites and control rats. These results suggest that splanchnic endotoxemia may be involved in the development and/or maintenance of hyperdynamic circulation.
Chu
C J
CJ
Department of Medicine, Taipei Veterans General Hospital, Taiwan, ROC.
Lee
F Y
FY
Wang
S S
SS
Chang
F Y
FY
Lin
H C
HC
Lu
R H
RH
Chan
C C
CC
Lee
S D
SD
D000818:Animals; D001201:Ascites / Q000503:physiopathology; D002251:Carbon Tetrachloride; D004731:Endotoxins / Q000097:blood*; D006439:Hemodynamics / Q000187:drug effects; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation; D014655:Vascular Resistance / Q000187:drug effects
D004731:Endotoxins; D002251:Carbon Tetrachloride