A model to study total hepatic ischemia-reperfusion injury.
BACKGROUND
Most experimental animal models for studying hepatic ischemia-reperfusion injury (IRI) involve partial or segmental ischemia of the liver or a portocaval shunt procedure to avoid mesenteric congestion. However, these do not reflect the global ischemia that occurs during liver transplantation. A rabbit model of total hepatic ischemia without a portocaval shunt is described.


METHODS
Twenty male New Zealand white rabbits (3.5 +/- 0.3 kg) were allocated to four groups: group 1 (n = 5), sham-operated; group 2 (n = 5), 20-minute total hepatic ischemia; group 3 (n = 5), 25-minute total hepatic ischemia; and group 4 (n = 5), 30-minute total hepatic ischemia. Total hepatic ischemia was induced by occluding the portal inflow vessels (portal vein and artery) with an atraumatic vascular loop and were measurements taken for 2 hours during reperfusion.


RESULTS
A total hepatic ischemia of 30 minutes caused severe liver injury resulting in cardiac arrest at 2 hours of reperfusion in all five animals due to metabolic acidosis. Twenty minutes of total ischemia was tolerated and did not produce significant liver injury. Twenty-five minutes of total ischemia was tolerated but at 2 hours of reperfusion, resulted in significant liver injury (68 +/- 41, 283.0 +/- 20.5, and 835.2 +/- 52.7 U/L) compared with the sham-operated group (serum ALT, 25.4 +/- 2.7; serum AST, 47.4 +/- 3.0; serum LDH, 307.6 +/- 44.4 U/L; P < .003).


CONCLUSIONS
Rabbits can tolerate 25 minutes of total hepatic ischemia without a portosystemic shunt. This 25-minute ischemia model simulates operative conditions during liver transplantation and will be valuable in studies modulating IRI.
Kanoria
S
S
Hepato-biliary and Liver Transplant Unit, Academic Department of Surgery, Royal Free Hospital, London NW3 2QG, UK.
Glantzounis
G
G
Jalan
R
R
Davies
N A
NA
Seifalian
A M
AM
Williams
R
R
Davidson
B R
BR
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001794:Blood Pressure; D004195:Disease Models, Animal; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008102:Liver Circulation; D010100:Oxygen / Q000097:blood; D011817:Rabbits; D015427:Reperfusion Injury / Q000201:enzymology / Q000503:physiopathology*; D013997:Time Factors
D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D010100:Oxygen