Warm ischemia and reperfusion injury in diet-induced canine fatty livers.
BACKGROUND
Fatty liver is associated with primary nonfunction after liver transplantation, contributing a shortage of suitable liver grafts. Because extensive investigation of mechanisms underlying such nonfunction has been limited largely to rodents, we made a new fatty liver model in dogs and studied primary nonfunction after warm ischemia.


METHODS
We developed a diet rich in fat but deficient in choline to induce fatty change in canine liver and investigated effects of 60 min of warm ischemia and reperfusion in dogs with such fatty livers.


RESULTS
Microscopically evident steatosis increased with duration of dietary manipulation (up to 12 weeks), as did hepatic total lipid and triglyceride levels. No dog with >30% of steatotic hepatocytes, >445 mg/g hepatic total lipid or >145 mg/g hepatic triglyceride survived after 60 min of warm ischemia. Arterial ketone body ratios decreased and blood endotoxin increased after reperfusion in nonsurvivors. The main histologic finding in livers of nonsurvivors was marked sinusoidal congestion.


CONCLUSIONS
Damage to hepatocytes and nonparenchymal cells after warm ischemia and reperfusion was thought to be closely related to sinusoidal microcirculatory disturbances in fatty livers. The canine fatty liver model reported here may be useful in studying the pathology of primary nonfunction and in establishing criteria for allowable degrees of fatty change in potential liver grafts.
Takahashi
K
K
Second Department of Surgery, Hirosaki University School of Medicine, Japan. hakamada@cc.hirosaki-u.ac.jp
Hakamada
K
K
Totsuka
E
E
Umehara
Y
Y
Sasaki
M
M
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002784:Cholesterol / Q000097:blood; D002796:Choline Deficiency; D004041:Dietary Fats; D004285:Dogs; D004731:Endotoxins / Q000097:blood; D005234:Fatty Liver / Q000503:physiopathology*; D005260:Female; D007511:Ischemia; D050356:Lipid Metabolism; D008099:Liver / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D015427:Reperfusion Injury; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
D004041:Dietary Fats; D004731:Endotoxins; D010743:Phospholipids; D014280:Triglycerides; D002784:Cholesterol; D000410:Alanine Transaminase; C029310:lard