Regeneration of ATP in kidney slices after warm ischemia and hypothermic preservation

The current shortage of cadaveric kidneys may be alleviated to some degree by increasing our capabilities to use less than ideal donor kidneys, such as those from non-heart-beating donors. These kidneys are often exposed to no flow (ischemia) for varying lengths of time. Full utilization of these kidneys may require better methods of organ preservation that could reverse existing ischemic injury. This may conceivably require that, during preservation, energy stores (ATP) lost during warm ischemia be recharged. This would required continuous perfusion. Using a kidney slice model, we investigated the effects of simulated hypothermic machine perfusion with the UW gluconate perfusate on the capability of rabbit kidneys exposed to warm ischemia to regenerate ATP. After 30 min of warm ischemia, ATP content was low (0.2 mumol/g wet weight) but increased to 0.7-0.9 mumol/g wet weight after 24 h of simulated machine perfusion at 4 degrees C. After an additional 2 h of rewarming (37 degrees C in oxygenated Krebs Henseleit buffer), the slice ATP content increased to about 1.0 mumol/g wet weight (similar to kidneys not exposed to warm ischemia) when the antioxidants desferrioxamine and N-2-(mercaptopropionyl) glycine were included in the preservation media. Significantly less ATP was present without the antioxidants. After 60 min of warm ischemia, less ATP was regenerated after 24 h of simulated machine perfusion (about 0.4 mumol/g wet weight) than after 30 min of warm ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)