engleski

[SA-PO3046] Renal Protection from Cold Ischemia in Hibernating Mammals

We have previously shown that cold ischemia (CI) results in an increase in caspase-3 activity, increased tubular apoptosis, and brush border injury (BBI) in mouse kidneys. The 13-lined ground squirrel (Ictidomys tridecemlineatus) is a hibernating mammal found in the central US. It undergoes yearly hibernation of ~ 6 months, during which time core body temperature (CBT) falls to 2-4°C for up to 5-18 days at a time. Since hibernation is a normal part of the animal's life-cycle, we hypothesized that squirrel kidneys were protected from tubular injury caused by CI. Methods: The kidneys of 1-2 year old summer squirrels were perfused with cold University of Wisconsin (UW) solution. The contralateral right kidney was immediately used as a control and the left kidney was stored in UW for 72 hours at 4°C. The % of tubules displaying BBI were counted and scored by a pathologist as follows: 0 = no changes, 1 = <10%, 2 = 11-25%, 3 = 26-45%, 4 = 46-75%, 5 > 75%. Apoptotic tubular cells were identifed and counted using the following morphologic criteria: cellular rounding and shrinkage, nuclear chromatin compaction and formation of apoptotic bodies. Caspase-3/7 activity was measured using the fluorescent substrate DEVD-AMC.Results. There was a small increase in caspase-3/7 activity in the squirrel kidneys vs. a massive increase in the mouse kidneys. There was no increase in apoptosis or BBI after 72 hours of cold ischemia compared to a significant increase in mice. Conclusion. We have shown that 13-lined ground squirrel kidneys are resistant to severe kidney injury during prolonged CI. This protection appears to be due in part to markedly reduced caspase-3/7 activity, and reduced apoptosis. Remarkably, after 72 hours of CI, there was no significant increase in BBI. Further study of the mechanisms by which this protection is achieved is warranted.

cold ischemia; apoptosis; squirrels

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