Role of ischemic preconditioning and the portosystemic shunt in the prevention of liver and lung damage after rat liver transplantation.
BACKGROUND
This study evaluates whether surgical strategies such as the portosystemic shunt and ischemic preconditioning can protect against hepatic and pulmonary injury associated with liver transplantation.


METHODS
The effect of the portosystemic shunt, ischemic preconditioning, and both surgical procedures together were evaluated in rat liver transplantation. Alanine aminotransferase, hyaluronic acid levels in plasma, adenosine triphosphate and nucleotide levels in liver and edema, malondialdehyde levels, and myeloperoxidase activity were measured 24 hr posttransplantation. Plasmatic tumor necrosis factor (TNF) levels were measured as a possible proinflammatory factor responsible for hepatic and pulmonary damage associated with liver transplantation.


RESULTS
Hepatocyte and cell endothelial damage were observed in liver grafts subjected to 8 hr of cold ischemia. This was associated with increased plasma TNF levels and lung inflammatory response. Portosystemic shunt application in the recipient protected endothelial cells but did not confer an effective protection from hepatocyte damage or reduce the increased plasma TNF levels and lung damage after liver transplantation. However, preconditioning of the donor liver conferred protection against both the endothelial cell and hepatocyte damage observed after liver transplantation. Preconditioning also attenuated the increased plasma TNF release and pulmonary damage. The combination of both surgical strategies resulted in levels of liver injury, TNF, and lung damage similar to those seen after liver transplantation.


CONCLUSIONS
These findings indicate that ischemic preconditioning could be a preferred treatment to reduce hepatic and pulmonary damage associated with liver transplantation. However, this strategy may not be effective in several clinical situations requiring a portosystemic shunt.
Fernández
L
L
Department of Experimental Pathology, Instituto de Investigaciones August Pi i Sunyer, Consejo Superior de Investigaciones Científicas, Barcelona, Spain.
Heredia
N
N
Peralta
C
C
Xaus
C
C
Roselló-Catafau
J
J
Rimola
A
A
Marco
A
A
Serafín
A
A
Deulofeu
R
R
Gelpí
E
E
Grande
L
L
D000818:Animals; D003080:Cold Temperature; D004734:Energy Metabolism; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D019194:Ischemic Preconditioning; D008107:Liver Diseases / Q000473:pathology / Q000517:prevention & control* / Q000601:surgery; D016031:Liver Transplantation; D008171:Lung Diseases / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D011170:Portasystemic Shunt, Surgical; D011183:Postoperative Complications / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha