Intravenous glycine improves survival in rat liver transplantation

• Published in: American journal of physiology: Gastrointestinal and liver physiology 1999-04, Vol.276 (4), p.G924-G932
• Main Authors: Schemmer, Peter, Bradford, Blair U., Rose, Michelle L., Bunzendahl, Hartwig, Raleigh, James A., Lemasters, John J., Thurman, Ronald G.
• Format: Article
• Language: English
• ISSN: 0193-1857; 1522-1547
• DOI: 10.1152/ajpgi.1999.276.4.G924

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 GdCl 3 , 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-α 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.