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Changes in gut function during hibernation: implications for bowel transplantation and surgery
  1. H V CAREY
  1. Department of Comparative Biosciences
  2. School of Veterinary Medicine, University of Wisconsin
  3. Madison, WI 53706, USA
  4. Division of Transplantation Surgery
  5. Medical School, University of Wisconsin
  6. Madison, WI 53706, USA
  1. Dr H V Carey. careyh{at}

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Organ transplantation has become routine in many centres throughout the world. Although success rates for intestinal transplantation are generally lower than for other organs, it is still high enough to warrant this form of therapy for patients with short bowel syndrome or other untreatable bowel diseases. Much of the success in transplantation is due to the impact of immunosuppressive drugs as well as the development of new surgical techniques and new methods of organ preservation. The intestine has been preserved successfully for about 24 hours, as judged by in vitro viability assessment1 and by survival after transplantation.2 However, problems associated with extended cold storage, ischaemia/reperfusion injury, and immunological rejection of grafts still limit the optimal use of intestinal transplantation. The benefit of hypothermic organ preservation is generally attributed to the reduction in oxygen and nutrient demands and in the rates of potentially damaging enzyme catalysed reactions. However, lack of oxygen in cold stored organs gradually leads to a time dependent loss of ATP, with rates of degradative reactions exceeding biosynthesis. In addition, prolonged hypothermia alters cell structure (for example, cytoskeletal proteins), reduces ion pump activity, and slows ATP synthesis. These changes, coupled with oxidative stress secondary to ischaemia-reperfusion injury and immunological factors, eventually lead to loss of metabolic control and critical membrane functions that compromise organ survival on reperfusion. The result for the cold stored transplanted bowel is too often mucosal destruction, loss of absorptive and barrier function, and eventual graft rejection.

Improvements in intestinal preservation could increase organ availability and perhaps more importantly the likelihood that a transplant is successful. To this end, novel insights may be found in animals that naturally experience extreme changes in physiology, particularly hypoxia and hypothermia. Mammalian hibernators offer the unique opportunity to examine what is essentially Nature's version of organ preservation. …

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