Liver metabolism in cold hypoxia: a comparison of energy metabolism and glycolysis in cold-sensitive and cold-resistant mammals

Churchill, Thomas A.; Cheetham, K; Simpkin, S.; Green, C. J.; Wang, Lawrence C.H.; Fuller, Barry

doi:10.1007/bf00302556

Cited by 20 publications

(13 citation statements)

References 22 publications

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“…Preliminary studies indicate that greater tolerance of sinusoidal endothelial cells to cold storage/warm reperfusion may be one mechanism for enhanced tolerance in the torpid squirrel livers (52). Studies by other investigators using a different species, the Columbian ground squirrel, provided no evidence for superior maintenance of adenylate levels after several hours of cold storage of livers from torpid squirrels compared with euthermic squirrels or rats (62,63). Elucidation of the mechanism(s) that underlie the increased tolerance to cold storage displayed by torpid hibernators, and strategies to adapt this information to organ preservation could have a profound effect on the quality, duration, and availability of human organs for transplantation.…”

Section: Organ Preservationmentioning

confidence: 90%

Mammalian Hibernation: Cellular and Molecular Responses to Depressed Metabolism and Low Temperature

Carey

Andrews

Martin

2003

Physiological Reviews

996

955

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Mammalian hibernators undergo a remarkable phenotypic switch that involves profound changes in physiology, morphology, and behavior in response to periods of unfavorable environmental conditions. The ability to hibernate is found throughout the class Mammalia and appears to involve differential expression of genes common to all mammals, rather than the induction of novel gene products unique to the hibernating state. The hibernation season is characterized by extended bouts of torpor, during which minimal body temperature (Tb) can fall as low as -2.9 degrees C and metabolism can be reduced to 1% of euthermic rates. Many global biochemical and physiological processes exploit low temperatures to lower reaction rates but retain the ability to resume full activity upon rewarming. Other critical functions must continue at physiologically relevant levels during torpor and be precisely regulated even at Tb values near 0 degrees C. Research using new tools of molecular and cellular biology is beginning to reveal how hibernators survive repeated cycles of torpor and arousal during the hibernation season. Comprehensive approaches that exploit advances in genomic and proteomic technologies are needed to further define the differentially expressed genes that distinguish the summer euthermic from winter hibernating states. Detailed understanding of hibernation from the molecular to organismal levels should enable the translation of this information to the development of a variety of hypothermic and hypometabolic strategies to improve outcomes for human and animal health.

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Section: Organ Preservationmentioning

confidence: 90%

Mammalian Hibernation: Cellular and Molecular Responses to Depressed Metabolism and Low Temperature

Carey

Andrews

Martin

2003

Physiological Reviews

996

955

View full text Add to dashboard Cite

show abstract

“…Hypothermic and hypoxic stress during cold preservation leads to ATP depletion and deterioration of the intracellular homeostasis, resulting in disruption of intercellular contact and denudation in sinusoidal endothelial cells and glycolysis in hepatocytes (24–27). Subsequent warm reperfusion period has more complex features including impairment of microcirculation, ROS production, cytokine production, and expression of adhesion molecules and extravasation of host leukocytes.…”

Section: Discussionmentioning

confidence: 99%

Critical Role of Interferon Regulatory Factor-1 in Murine Liver Transplant Ischemia Reperfusion Injury

et al. 2010

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“…Despite the obvious parallels between hibernation and organ preservation, few studies have examined whether mammalian hibernators display enhanced abilities to withstand the deleterious effects of prolonged cold ischemia compared with summer euthermic individuals of the same species or with nonhibernating species. Churchill et al (8,9) studied livers from euthermic and hibernating Columbian ground squirrels that were fresh or preserved at 4°C for up to 72 h and found no differences between euthermic and torpid ground squirrels in hepatic glycolytic enzyme activities or tissue adenylate levels after cold preservation; the fall in adenylate levels in livers over a 24-h period of cold ischemia was similar in hibernating and euthermic animals (9). Anaerobic glycolysis was also similar in the two groups, as indicated by increasing lactate levels over the ischemic period.…”

Section: Discussionmentioning

confidence: 99%

Natural resistance to liver cold ischemia-reperfusion injury associated with the hibernation phenotype

Lindell¹,

Klahn²,

Piazza³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

117

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. Natural resistance to liver cold ischemia-reperfusion injury associated with the hibernation phenotype. Am J Physiol Gastrointest Liver Physiol 288: G473-G480, 2005; doi:10.1152/ajpgi.00223.2004.-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 (T b) 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 (T b Ͻ 10°C) or aroused (Tb ϭ 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 DESPITE MAJOR ADVANCES IN hypothermic preservation of organs before transplant, problems associated with extended cold ischemia-reperfusion (cold I/R) injury still limit the optimal use of transplantation as a therapeutic intervention for organ failure. For example, human livers can be successfully stored at 4°C for up to 12 h in University of Wisconsin (UW) solution, but graft failure is greatly increased after extended storage periods (14,33,34). In the rat liver transplant model, when livers are cold stored in UW for up to 24 h, 100% of the recipients survive (42); in contrast, without nutritional manipulation, none survive after receiving livers stored for 48 h (39).The damaging effects of cold I/R are evident on organ reperfusion with warmed, oxygenated blood, with damage increasing with the length of the cold ischemia period (10,35,40).A variety of pharmacological strategies has been explored to improve graft function after cold I/R to extend cold storage times and provide more flexibility in organ distribut...

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Liver metabolism in cold hypoxia: a comparison of energy metabolism and glycolysis in cold-sensitive and cold-resistant mammals

Cited by 20 publications

References 22 publications

Mammalian Hibernation: Cellular and Molecular Responses to Depressed Metabolism and Low Temperature

Mammalian Hibernation: Cellular and Molecular Responses to Depressed Metabolism and Low Temperature

Critical Role of Interferon Regulatory Factor-1 in Murine Liver Transplant Ischemia Reperfusion Injury

Natural resistance to liver cold ischemia-reperfusion injury associated with the hibernation phenotype

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