A model to study total hepatic ischemia-reperfusion injury

Abstract

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.