Ischemic injury in liver transplantation: difference in injury sites between warm and cold ischemia in rats.
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.
Ikeda
T
T
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Yanaga
K
K
Kishikawa
K
K
Kakizoe
S
S
Shimada
M
M
Sugimachi
K
K
D000818:Animals; D006820:Hyaluronic Acid / Q000097:blood; D007511:Ischemia / Q000209:etiology*; D007728:Kupffer Cells / Q000502:physiology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D010587:Phagocytosis; D051381:Rats; D011917:Rats, Inbred Lew; D013696:Temperature; D014184:Transplantation, Homologous; D014655:Vascular Resistance
D006820:Hyaluronic Acid; D007770:L-Lactate Dehydrogenase