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LIVER AND BILIARY TRACT
1Department of Comparative Biosciences, University of Wisconsin School of Veterinary Medicine, 2Department of Surgery, University of Wisconsin School of Medicine, Madison, Wisconsin; and 3Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
Submitted 14 May 2004 ; accepted in final form 17 October 2004
The success of liver grafts is currently limited by the length of time organs are cold preserved before transplant. Novel insights to improve viability of cold-stored organs may emerge from studies with animals that naturally experience low body temperatures (Tb) for extended periods. In this study, we tested whether livers from hibernating ground squirrels tolerate cold ischemia-warm reperfusion (cold I/R) for longer times and with better quality than livers from rats or summer squirrels. Hibernators were used when torpid (Tb < 10°C) or aroused (Tb = 37°C). Livers were stored at 4°C in University of Wisconsin solution for 0–72 h and then reperfused with 37°C buffer in vitro. Lactate dehydrogenase (LDH) release after 60 min was increased 37-fold in rat livers after 72 h cold I/R but only 10-fold in summer livers and approximately three- to sixfold in torpid and aroused hibernator livers, despite twofold higher total LDH content in livers from hibernators compared with rats or summer squirrels. Reperfusion for up to 240 min had the least effect on LDH release in livers from hibernators and the greatest effect in rats. Compared with rats or summer squirrels, livers from hibernators after 72 h cold I/R showed better maintenance of mitochondrial respiration, bile production, and sinusoidal lining cell viability, as well as lower vascular resistance and Kupffer cell phagocytosis. These results demonstrate that the hibernation phenotype in ground squirrels confers superior resistance to liver cold I/R injury compared with rats and summer squirrels. Because hibernation-induced protection is not dependent on animals being in the torpid state, the mechanisms responsible for this effect may provide new strategies for liver preservation in humans.
transplantation; cold storage; Kupffer cells; sinusoidal lining cells
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