Enhanced monocyte activation and hepatotoxicity in response to endotoxin in portal hypertension
Section snippets
Animal preparation
Male Sprague-Dawley rats (weight 250–300 g) were obtained from Charles River, (Saint Aubin-lès-Elbeuf, France). Portal hypertension was induced as described (19) by partial portal vein ligation (PPVL) under ketamine anesthesia (Ketalar, 100 μg/kg body wt intramuscularly; Parke Davis, Inc., Morris Klein, NJ, USA). In brief, the portal vein was isolated and a calibrated constriction was performed using a single ligature of 3-0 silk around the portal vein and a 20-gauge blunt-tipped needle, which
Hemodynamics
Two weeks after ligation of the portal vein, PPVL rats had higher portal pressure (15.2±2.4 mmHg vs. 8.7±1.5 mmHg, p<0.05) and lower mean arterial pressure (104±4 mmHg vs.129±1 mmHg, p<0.05) than SHAM rats. Body weight at the time of the study was similar: 332±7 g in PPVL rats and 327±6 g in SHAM animals. The treatment with low doses of LPS (150 μg/kg ) had no significant effect on the mean arterial or portal pressure, and the significant differences between PPVL and SHAM animals were
Discussion
Septic shock is a multimediator disease. A large number of homeostatic systems may contribute directly or indirectly to the pathophysiology of septic shock, but no single mediator can explain all the features of this clinical entity. Moreover, there appears to be a complex interplay linking various systems to each other (3). Bacterial infections by Gram-negative organisms (including bacteremia, sepsis and spontaneous bacterial peritonitis) are usual complications in patients with cirrhosis and
Acknowledgements
We thank Dr. Deulofeu and Dr. Mas for technical assistance.
This study was supported by grants from the Comisión Interministerial de Ciencia y Tecnología (SAF 96-0120) (PB 94–1562) and Fundació Clínic per a la Recerca Biomèdica. SPP is a recipient of a grant from Formación del Personal Investigador (FP95 46731316).
References (36)
- et al.
Serum cytokine levels in human septic shock. Relation to multiple-system organ failure and mortality
Chest
(1993) - et al.
Pathophysiology of portal hypertension
Gastroenterol Clin North Am
(1992) - et al.
Role of endothelium in the abnormal response of mesenteric vessels in rats with portal hypertension and liver cirrhosis
Gastroenterology
(1996) - et al.
Acute and chronic cycloxigenase blockade in portal-hypertensive rats: influence on nitric oxide biosynthesis
Gastroenterology
(1996) - et al.
Modulation of the hyperdynamic circulation of cirrhotic rats by nitric oxide inhibition
Gastroenterology
(1992) - et al.
Nitric oxide mediates hyporeactivity to vasopressors in mesenteric vessels of portal hypertensive rats
Gastroenterology
(1992) - et al.
Portal hypertension enhances endotoxin-induced intercellular adhesion molecule 1 up-regulation in the rat
Gastroenterology
(1996) - et al.
Tumor necrosis factor α: a major contributor to the hyperdynamic circulation in prehepatic portal-hypertensive rats
Gastroenterology
(1995) - et al.
Role of cytokines in sepsis
Adv Immunol
(1997) - et al.
Molecular mechanims of signal transduction in macrophages
Immunol Today
(1987)