This study suggests that steatotic livers can be successfully preserved using normothermic preservation for prolonged periods and that normothermic preservation facilitates a reduction in hepatic steatosis. Further studies are now needed including transplantation of steatotic livers after normothermic preservation.
Liver transplantation is the treatment of choice for many patients with acute and chronic liver failure, but its application is limited by a shortage of donor organs. Donor organ shortage is the principal cause of increasing waiting lists, and a number of patients die while awaiting transplantation. Non -heart-beating donor (NHBD) livers are a potential means of expanding the donor pool. This is not a new concept. Prior to the recognition of brainstem death, organs were retrieved from deceased donors only after cardiac arrest. Given the preservation techniques available at that time, this restricted the use of extrarenal organs for transplantation. In conclusion, after establishment of brain death criteria, deceased donor organs were almost exclusively from heart-beating donors (HBDs). Categories 1 and 2 are termed "uncontrolled" (UCNHBD), as there is no time to organize the process of organ donation and there is a brief window of opportunity for organ retrieval. These donors are often patients who present to the emergency department. After declaration of death, organ donation is considered. Permission from the family for organ donation is usually sought after cardiac arrest. As the process of retrieval is only initiated after the declaration of death, these organs necessarily suffer a prolonged period of warm ischemia. Category 3 is termed "controlled" (CNHBD), as there is opportunity to obtain family consent and mobilize the retrieval team prior to withdrawal of support. For this reason, warm ischemia time can be reduced.
Warm Ischemia TimeThe first international workshop in Maastricht, the Netherlands, held in 1995, recommended that warm ischemia should be counted from the moment of cardiac arrest until the start of hypothermic flush out. 2 There is a lack of uniform definition used in the published literature for liver transplantation. It has been variously defined as time between withdrawal of support and cold flushing of the organs, 3 time between hypotension (blood pressure Ͻ35 mm Hg) or low oxygen saturation (Ͻ25%) and flushing of the organs, 4 or time from extubation to aortic cross clamp. 5 A standardized definition and uniform application of warm ischemia time is needed for scientific comparison and interpretation of clinical results.
The ProblemThe fundamental problem with NHBD organs is prolonged warm ischemia. Organ preservation and transplantation is associated with ischemia reperfusion injury. Cold preservation at 4°C slows metabolism and provides a milieu to limit the effect of ischemia. Although metabolism is slowed 1.5-to 2-fold for every 10°C drop in temperature, considerable metabolic activity still occurs at 1°C. 6 Adenosine triphosphate (ATP) is depleted and lack of oxygen converts aerobic metabolism to anaerobic metabolism, leading to accumulation of lactate and hypoxanthine, and development of intracellular acidosis. ATP is required to maintain the integrity of sodium / potassium pumps that
Normothermic preservation has been shown to be advantageous in an experimental model of preservation of nonheart-beating donor (NHBD) livers, which have undergone significant warm ischemic injury. The logistics of clinical organ retrieval might dictate a period of cold preservation prior to warm perfusion. We have investigated the effects of a brief period of cold preservation on NHBD livers prior to normothermic preservation. Porcine livers were subjected to 60 minutes of warm ischaemia and then assigned to following groups: Group W (n ؍ 5), normothermic preservation for 24 hours; and Group C (n ؍ 6), cold preservation in University of Wisconsin solution for 1 hour followed by normothermic preservation for 23 hours (total preservation time, 24 hours). Synthetic function (bile production and factor V production) and cellular damage were compared on the ex vivo circuit during preservation. There was no significant difference in the synthetic function of the livers (bile production and factor V production).
Alemtuzumab (CAMPATH-1H) is a depleting agent introduced recently in transplantation and often used with reduced maintenance immunosuppression. In the current study we investigated the immune response of 13 kidney allograft recipients treated with alemtuzumab followed by weaned immunosuppression with reduced dose of mycophenolate mofetil (MMF) and tacrolimus. Tacrolimus was switched to sirolimus at 6 months and MMF withdrawn at 12 months after transplantation.We found that after alemtuzumab induction the recovery of CD8 + T cells was much faster than that of CD4
We performed a pilot study in which 22 kidney recipients (14 LD: 8 DCD) were given alemtuzumab induction (30 mg day 0 and 1), steroids (500 mg mp day 0 and 1, none thereafter), mycophenolate mofetil (
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