Liver regeneration after hepatic ischemia and reduced liver autotransplantation in the rat

Abstract

Current knowledge of liver regeneration after reduced liver transplantation is limited. Warm ischemia is one component of the reduced liver transplantation procedure that could have an impact on the regenerative response. To study this effect, we performed partial hepatectomy on male Long-Evans rats, with animals divided into four groups: group 1 underwent partial hepatectomy only; group 2 underwent partial hepatectomy and 40 min of ischemia; group 3 underwent partial hepatectomy, 40 min of ischemia and portocaval shunt surgery; and group 4 underwent partial hepatectomy and orthotopic autograft surgery. Group 5 consisted of sham-operated animals. Animals were killed 4, 24, 48, 72 and 96 hr after surgery. Thymidine kinase activity, mitotic index, a liver mass index and ornithine decarboxylase levels were used as parameters of liver regeneration. Aspartate transaminase was recorded. Maximal thymidine kinase and mitotic index were observed in group 1 animals at 24 hr. In groups 2, 3 and 4 maximal thymidine kinase activity and mitotic activity were observed 24 hr later at 48 hr. The magnitude of the peak response in these groups appeared to correlate with the duration of portal venous occlusion, with greatest increases occurring in those groups where portal stasis was most prolonged. The increase in liver mass for these groups was also delayed with respect to group 1 animals. The anticipated peak in ornithine decarboxylase levels was seen at 4 hr in group 1. The ornithine decarboxylase response in the other groups was disorganized, with delay of the recorded peaks.(ABSTRACT TRUNCATED AT 250 WORDS)

Beneficial Effect of Deletion Variant of Hepatocyte Growth Factor for Impaired Hepatic Regeneration in the Ischemically Damaged Liver

“…However, it is anticipated that ischemia is a critical factor associated with the impaired regenerative capacity of the liver [8]. Data on regeneration of ischemically damaged livers were available in some experimental studies, but the issue of regenerative capacity remains controversial because the differences in regenerative response between normal and ischemically damaged livers have been insufficiently clarified under these conditions [7][8][9][10].…”

Ischemia impairs liver regeneration after major tissue loss in rodents: Protective effects of interleukin-6

“…Both positive and negative effects have been reported. [8][9][10][11] Bolitho et al 10 found significant negative effects of 40 minutes of ischemia on several markers of hepatocyte proliferation after major liver resection in the rats. However, in this model a portacaval shunt was performed after initiating clamping of the portal triad resulting in incomplete mesenteric decompression.…”

“…7 The effects of ischemia on hepatic regeneration have not been extensively studied, and the available data provide conflicting results. [8][9][10][11] Although some groups reported adverse effects of ischemia on the regenerative ability of the liver, [9][10][11] other authors found that a period of 30 minutes of ischemia can enhance hepatocyte proliferation. 8 The differences among these results are unclear and might be related to the duration of ischemia, the clamping technique to induce hepatic ischemia, the presence of concomitant mesenteric congestion, and the parameters of regeneration evaluated.…”

Effects of Re-Arterialization on Early Graft Function and Regeneration in the Rat Model of Heterotopic Auxiliary Liver Transplantation

“…This increase in DNA synthesis rate was presumably due to a 'first pass' of portal hepatotrophic factors flowing through the partial hepatectomized graft. The 24-hour delay of the initial peak compared with that after a standard two-third partial hepatectomy [21] could be due to ischemic damage and operative stress [22]. Remarkably, the re-arterialized rats revealed a more pronounced regenerative response than the non-re-arterialized rats despite equivalent portal blood supply.…”

“…It is known that warm ischemia during the transplantation procedures causes depletion of ATP, which directly induces damage to the hepatocytes [25] and impairs the general hepatic functions such as protein synthesis and bile secretion [26]. The initial regeneration response is also depressed [22]. Re-arterialization does improve the hepatic oxygen sup-Fan/Praet/Vanzieleghem/Vanwynsberghe/ Stoop/Leroux-Roels/Delanghe/ de Hemptinne ply needed for an increased ATP synthesis in the liver graft [8], so that the significantly high DNA synthesis rate shown in the re-arterialized rats of this study may be directly attributed to reduced warm ischemic injury of the engrafted liver.…”