Data from recent studies suggest that donor fasting imparts a beneficial effect on the viability of transplanted hepatic allografts. Because starvation may temporarily inactivate Kupffer cells, and because these cells are the likely mediators of liver injury after prolonged preservation‐reperfusion, the purpose of this study is to establish a link between improved organ viability and Kupffer cell inactivation caused by donor allograft fasting. In an in vivo rat liver transplant model, 48 hours of donor fasting (1) improved allograft viability, (2) significantly decreased Kupffer cell phagocytosis, and (3) significantly decreased cytokine (tumor necrosis factor [TNF]) production postrevascularization. These data validate work from previous studies demonstrating that donor fasting improves allograft viability and furthermore support our previous research implicating activation of Kupffer cells as a causative agent of cold ischemia‐preservation injury. (HEPATOLOGY 1995; 22:1236–1242.).
Preservation-reperfusion injury of hepatic allografts is thought to be associated with Kupffer cell activation and TNF release from the transplanted organ. Confirmation that the allograft is the source of this TNF in an in vivo model is difficult because of rapid equilibration of this cytokine into all compartments. A novel experimental design was devised to aid in accurate localization of the site of TNF release following a orthotopic liver transplant (OLT). In the first group (anhepatic), livers were removed from rats and splanchnic and systemic venous returns were then reestablished using a conduit of donor IVC and portal vein with a portasystemic shunt. In the second group (asplanchnic), the liver, stomach, pancreas, and intestine of the recipient were removed and a donor liver was reimplanted using the recipient IVC as the source of portal blood. The third (OLT-16) and fourth (OLT 8) groups underwent standard OLT with preservation times of 16 and 8 hr in 4 degrees C Euro-Collins solution, respectively. TNF levels were significantly increased in the OLT-16 group compared with the OLT-8 group. There were modest elevations of TNF in the anhepatic model, but the TNF in the asplanchnic model approached baseline. Absence of TNF in the asplanchnic group and a rise in TNF levels in the anhepatic group to that not significantly different from OLT-16 or OLT-8 suggest that a major source of TNF following preservation reperfusion may be the intestine.
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