Leukocyte and platelet depletion protects the liver from damage induced by cholestasis and ischemia-reperfusion in the dog.
BACKGROUND
Ischemia-reperfusion injury has been studied in various organs. The effects of leukocyte and platelet depletion on cholestasis and ischemia-reperfusion-induced liver damage were evaluated in the dog liver.


METHODS
The left hepatic duct was ligated for 4 weeks to create a cholestatic lobe. An ischemic condition was produced for 60 min by stopping the peristaltic pump supplying blood to the liver. The metabolism of substances modulated in the liver during cholestasis and I-R was assessed in non-treated and in leukocyte- and platelet-depleted animals.


RESULTS
The extraction rate of insulin and indocyanine green decreased during cholestasis and ischemia-reperfusion. Cholestasis accelerated the release of thromboxane A2 but not prostaglandin I2 after ischemia-reperfusion. Ischemia-reperfusion accelerated the release of prostaglandin I2 and thromboxane A2 from the liver. Further, ischemia-reperfusion increased the ratio of thromboxane A2 to prostaglandin I2. Cholestasis promoted an increase in the level. Ischemia-reperfusion caused an increase in the lipid peroxide level, and no change in the alpha-tocopherol level. Ischemia-reperfusion caused an increase in the lipid peroxide level, a decrease in the alpha-tocopherol level, and no change in the glutathione level. Depletion of leukocytes and platelets reduced these changes during cholestasis and ischemia-reperfusion.


CONCLUSIONS
Depletion of leukocytes and platelets thus appears to protect liver function from cholestasis and ischemia-reperfusion injury by reducing peroxidation of lipids composing the cell membrane and the rate of thromboxane A2 prostaglandin I2, which predicts cellular damage, and by increasing the levels of alpha-tocopherol and glutathione, believed to be free radical scavengers.
Kuroda
T
T
Dept. of Surgery, Shinshu University School of Medicine, Matsumoto, Japan.
Shiohara
E
E
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001651:Cholestasis, Extrahepatic / Q000097:blood*; D004285:Dogs; D011464:Epoprostenol / Q000097:blood; D005978:Glutathione / Q000097:blood; D007511:Ischemia / Q000097:blood*; D007958:Leukocyte Count; D015227:Lipid Peroxidation / Q000502:physiology; D008099:Liver / Q000098:blood supply*; D008111:Liver Function Tests; D010976:Platelet Count; D012039:Regional Blood Flow / Q000502:physiology; D015427:Reperfusion Injury / Q000097:blood*; D013928:Thromboxane A2 / Q000097:blood; D014810:Vitamin E / Q000097:blood
D014810:Vitamin E; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D005978:Glutathione