Injury During Preservation

Preservation of organs after retrieval is clearly one of the cornerstones of successful transplantation. Although organs vary in their tolerance to cold ischemia, injury to numerous cellular systems begins to occur immediately upon removal. Hypothermia suppresses, to a degree, these changes, but injury during hypothermia still occurs but at a slower rate. Since hypothermic-induced cell swelling is a major source of injury during preservation, most organ preservation solutions are formulated to prevent swelling at cold temperatures. The addition of impermeants such as gluconate, lactobionate, and saccharides such as raffinose, help prevent hypothermic-induced cellular swelling.

Several other phenomena have also been implicated in cell injury during preservation and have been studied extensively. Numerous cellular functions including maintenance of the cellular cytoskeleton requires energy in the form of adenosine triphosphate (ATP). Loss of energy-generating capabilities due to mitochondrial damage or loss of precursors will lead to irreversible cell injury and death upon reperfusion. This concept forms the basis for adding ATP precursors in the form of adenine, adenosine, and ribose to organ preservation solutions. Oxygen-free radical formation after reperfusion has also been implicated in cellular injury during preservation. Suppression of free-radical formation or the addition of free-radical scavengers such as allopurinol, may be beneficial in preservation solutions. Likewise, breakdown of cellular metabolites, such as glycogen and glutathione, may lead to injury and addition of these metabolites may be important in successful organ preservation. Also, activation of catabolic enzymes such as phospholipases and proteases and activation of the arachidonic cascade will lead to cell injury and methods to block their activation may lead to better organ preservation.

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