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Pathogenesis of endotoxemia and multiple organ failure in case of mechanical jaundice and their aggravation after the relief of cholestasis.

PURPOSE
To clarify the mechanisms of systemic endotoxemia in extrahepatic cholestasis and the pathogenesis of aggravation of multiorgan failure after external biliary drainage (EBD)--for elaborating of the curative tactics.


MATERIALS AND METHODS
The results of experimental studies performed on 208 Wistar rats and 90 dogs were implemented in the surgical clinic in treatment of 150 patients with cholestasis. In experiments--Histological, Transmission and Scanning Electron Microscopic, and Biochemical (Malonic Dialdehide--the end product of Peroxide Oxidation of Lipids of cell membrane) methods have been used. Perfect model of EBD in cholestasis was created. In clinic--the measurement of Mitochondrial ferments, Bilirubin concentration, Creatinin clearance and Psychometric tests were used for evaluation of liver, kidney and brain functions.


RESULTS
Destruction of 7.2% and 8.1% of villi in 6 and 7 days cholestasis and 17.3% and 23.5% of villi consequently in 12-14 days cholestasis (compared with 1.1%-1.4% in control [P < 0.01]) resulted in denudation of lacteals was observed. Malonic Dialdehide concentration is significantly increased in plasma after EBD in cholestasis, especially under rapid decreasing of biliary pressure.


CONCLUSION
Gut barrier failure in cholestasis "lets" gram-negative bacteria and their endotoxins to penetrate the systemic circulation via the lymphatic system avoiding the liver filter. This process, which is partially suppressed by bile salts existed in lymph due to bilio-lymphatic reflux, precipices just after EBD with all consequences. Aggravation of hepatic failure after one-stage rapid biliary decompression is also promoted by activation of Peroxide Oxidation of Lipids (caused by blood reflow into portal system under falling the pressure in bile compartment) injuring the liver cells. Administration of "Duphalac" ("Solvey Pharmaceuticals")--with antiendotoxic, and "Plapheron LB" (Georgian Industry)--with anti-free-radicals properties is suggested in cholestasis not only before the operation, but after the biliary drainage as well.