Studies of hepatic warm ischemia in the obese Zucker rat.
The effects of warm ischemia were investigated in obese Zucker rats with severe hepatic steatosis in order to develop a nontransplant fatty liver ischemia model. Obese (Ob) and lean (Ln) Zucker rats were subjected to in vivo partial hepatic warm ischemia of 45 or 90 min. Injury was assessed by serum alanine aminotransferase, animal survival, and liver histology. Liver lipids were quantified in control animals. After 90-min ischemia and 2-hr reperfusion, liver malondialdehyde was measured and neutrophils in 12 microscopic fields were counted after esterase staining. After 45 and 90 min of ischemia, Ob animals had significantly higher alanine aminotransferase at 1-hr and 24-hr reperfusion, compared with Ln animals (P < 0.01). After 90 min of ischemia, none of the Ln and 8/9 Ob animals died within 48 hr (P < 0.01). Histologically, Ob animals had more hepatocyte necrosis than did Ln animals. Hepatic neutral and phospholipid content (mg/g) in Ob versus Ln animals was 45.2 +/- 2.6 versus 8.2 +/- 0.7 (P < 0.01) and 36.2 +/- 1.9 versus 27 +/- 2.2 (P < 0.05), respectively. After reperfusion, liver malondialdehyde content increased significantly in Ob animals (8.5 +/- 0.4 vs. 12.3 +/- 0.8 pM/mg protein; P < 0.05), but not in Ln animals. Neutrophils, scant in control livers, increased significantly (P < 0.01) after ischemia/RP, but it increased to a similar degree in Ob and Ln animals. Obese Zucker rats with hepatic steatosis are more susceptible to warm ischemia/reperfusion injury than lean animals, and lipid peroxidation may be an important contributory mechanism. Further studies in this model might help to investigate the human problem.
Koneru
B
B
Department of Surgery, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark 07103, USA.
Reddy
M C
MC
dela Torre
A N
AN
Patel
D
D
Ippolito
T
T
Ferrante
R J
RJ
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D006358:Hot Temperature; D007511:Ischemia / Q000503:physiopathology*; D007958:Leukocyte Count; D008099:Liver / Q000098:blood supply* / Q000737:chemistry / Q000473:pathology; D008315:Malondialdehyde / Q000032:analysis; D009154:Mutation; D009504:Neutrophils / Q000166:cytology; D009765:Obesity / Q000097:blood / Q000235:genetics / Q000473:pathology; D051381:Rats; D011924:Rats, Zucker / Q000235:genetics*
D008315:Malondialdehyde; D000410:Alanine Transaminase