This study is designed to investigate the mechanisms involved in the loss of viability of dog kidneys during hypothermic perfusion preservation. The effects of perfusion on: 1) lipid metabolism, 2) release of lysosomal enzymes, 3) fragility of lysosomes, 4) integrity of the structure and function of cellular membranes and 4) pharmacological protection of metabolism of the kidney will be studied in detail. The effects of duration of hypothermic perfusion preservation on the rate of change of the lipid composition (phospholipids) of the whole organ and specific intracellular membrane systems will be determined. Also, the effects of preservation on the ratio of sedimentable and nonsedimentable lysosomal enzymes in kidney tissue will be determined as will the effects of preservation on the fragility of lysosomes. Specific pharmacological methods of suppressing degradative changes in lipid metabolism or lysosomal changes will be used and based upon results obtained in initial experiments. In addition, we will study methods of increasing the fluidity of cellular membranes of kidneys exposed to hypothermia in an attempt to convert the biophysical and biochemical properties of the cellular membranes of a normothermic organ to resemble membrane systems of hibernators. Model systems will be used in these studies including the effects of membrane fluidizer on the Arrhenius relationship of membrane-bound enzyme reactions and the fragility of red blood cell membranes to hypothermia. Our long range goal is to obtain long-term kidney preservation (7-10 days) by defining the mechanism of loss of kidney viability and prescribing appropriate methods (pharmacologically) to improve kidney viability.
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