At normal temperatures pumping mechanisms in cell walls retain intracellular potassium at high levels and extrude sodium. If these pumps fail sodium is taken up by the cell and potassium lost. Water follows the sodium passively and results in swelling of the cells. The importance of this control of cell swelling was demonstrated by McLoughlin who found a significant correlation between canine renal cortical water content and the ability of kidneys to support life after 36-hour storage. The pumping mechanism is driven by the enzyme system known as Na+K+- activated ATPase and is inhibited by cold. Levy found that metabolic activity at 10 °C, as indicated by oxygen consumption measurements, was reduced to about 5% of normal and, because all enzyme systems are affected in a similar way by hypothermia, ATPase activity is markedly reduced at 10 °C.
There are, however, tissue and species differences in the cold sensitivity of this ATPase which may account for the differences in the ability of tissues to withstand hypothermia. Martin has shown that in dog kidney cortical cells some ATPase activity is still present at 10 °C but not at 0 °C. In liver and heart cells activity was completely inhibited at 10 °C and this difference in the cold sensitivity of ATPase correlated with the greater difficulty in controlling cell swelling during hypothermic storage of liver and heart cells. A distinct ATPase is found in vessel walls, and this was shown by Belzer to be completely inhibited at 10 °C, when at this temperature kidney cortical cells ATPase is still active. These experiments were performed on aortic endothelium, but if the vascular endothelium of the kidney has the same properties, then vascular injury may be the limiting factor in prolonged kidney storage.
Willis has shown how hibernators derive some of their ability to survive low temperatures by having a Na+K+-ATPase which is able to transport sodium and potassium actively across their cell membranes, at 5 °C, about six times faster than in non-hibernators; this transport rate is sufficient to prevent cell swelling.
The rate of cooling of a tissue may also be significant in the production of injury to enzyme systems. Francavilla showed that when liver slices were rapidly cooled (immediate cooling to 12 °C in 6 minutes) anaerobic glycolysis, as measured on rewarming to 37 °C, was inhibited by about 67% of the activity that was demonstrated in slices that had been subjected to delayed cooling. However, dog kidney slices were less severely affected by the rapid cooling than were the liver slices.