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1 Laboratory of Hepatobiology
and Toxicology,
In situ manipulation by touching, retracting,
and moving liver lobes gently during harvest dramatically reduces
survival after transplantation (P. Schemmer, R. Schoonhoven, J. A. Swenberg, H. Bunzendahl, and R. G. Thurman.
Transplantation 65: 1015-1020, 1998). The development of harvest-dependent graft injury upon reperfusion can be prevented with
GdCl3, a rare earth metal and Kupffer cell toxicant, but it cannot be used in clinical liver transplantation because of its potential toxicity. Thus the effect of
glycine, which prevents activation of Kupffer cells, was assessed here.
Minimal dissection of the liver for 12 min plus 13 min without manipulation had no effect on survival (100%). However, gentle manipulation decreased survival to 46% in the control group.
Furthermore, serum transaminases and liver necrosis were elevated 4- to
12-fold 8 h after transplantation. After organ harvest, the rate of
entry and exit of fluorescein dextran, a dye confined to the vascular space, was decreased about twofold, indicating disturbances in the
hepatic microcirculation. Pimonidazole binding, which detects hypoxia,
increased about twofold after organ manipulation, and Kupffer cells
isolated from manipulated livers produced threefold more tumor necrosis
factor-
after lipopolysaccharide than controls. Glycine given
intravenously to the donor increased the serum glycine concentration
about sevenfold and largely prevented the effect of gentle organ
manipulation on all parameters studied. These data indicate for the
first time that pretreatment of donors with intravenous glycine
minimizes reperfusion injury due to organ manipulation during harvest
and after liver transplantation.
organ harvest; hepatic microcirculation; hypoxia
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