Ischemic injury in liver transplantation: Difference in injury sites between warm and cold ischemia in rats

Abstract

Using liver allografts with warm or cold ischemia, we evaluated functional and morphological alterations in hepatocytes, sinusoidal endothelial cells and Kupffer cells in a rat transplantation model. All recipients of allografts with either 4 hr of cold or 30 min of warm ischemia lived more than 22 days and were judged viable. On the other hand, all recipients of grafts with 6 hr of cold or 60 min of warm ischemia died within 2 days and were therefore judged to be nonviable. With these viable and nonviable allograft models, hepatocyte function was evaluated by the bile output and serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase and serum lactate dehydrogenase levels; endothelial cell function was judged by the serum hyaluronic acid level, and Kupffer cell function was measured by an intravenous colloidal carbon clearance test. Hepatocyte injury was the prominent feature in warm ischemic grafts, especially in the nonviable ones. On the other hand, serum hyaluronic acid values were significantly higher in the nonviable cold ischemic group, compared with the viable counterpart, suggesting that the functional depression of endothelial cells was predominant in cold, nonviable livers. Histological examinations coincided with the above findings. The phagocytic activity of Kupffer cells was depressed by warm or cold ischemia, whereas the number of Kupffer cells was reduced in the warm ischemia group. We conclude that in liver allografts the main site of injury in warm ischemia is the hepatocytes and suggest that cold ischemia is associated with endothelial cell damage.

A single-center experience with retrograde-reperfusion in liver transplantation

“…Times for ischemia, anastomosis and reperfusion are displayed in Table 1. During LTX 6,l (1-19) packed red cells, 10,7 (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) fresh frozen plasma and 1,9 (1-6) packed platelets were used. A total of 3248,3 ml (1077-8500) were vacuumed off with the cellsaver device.…”

Extended preservation of rat liver graft by induction of heme oxygenase-1

“…13,14,32,33 Sinusoidal endothelial cells are particularly vulnerable to apoptosis 13 and damage to endothelial cells leads to secondary hepatocellular injury and death. 34,35 Electron microscopy 8. The activation of the executioner caspase 3 was determined by immunohistochemistry by using an antibody specific for the activated caspase followed by morphometric analysis in a blinded fashion.…”

Liver transplantation: Yesterday, today and tomorrow

“…The pattern of injury sustained during warm and cold ischemia is slightly different. Cold ischemia leads to initial injury to sinusoidal endothelial cells whereas warm ischemia mainly injures the hepatocytes [30] . It seems that the additional injury resulting from warm ischemia in NHBD donation requires alternative preservation strategies to minimize the ischemic injury.…”