Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK018624-11
Application #
3226107
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1979-04-01
Project End
1987-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
11
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
University of Wisconsin Madison
Department
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715

  Publications

Knes, Jane M; Hansen, Thomas N; Gilligan, Barbara et al. (2005) Loss of endothelium-dependent relaxation in abdominal aorta preserved in a co-storage system. Transpl Int 17:699-706
Gilligan, Barbara J; Woo, Heung M; Kosieradzki, Maciej et al. (2004) Prolonged hypothermia causes primary nonfunction in preserved canine renal allografts due to humoral rejection. Am J Transplant 4:1266-73
Mangino, Martin J; Ametani, Mary; Szabo, Csaba et al. (2004) Poly(ADP-ribose) polymerase and renal hypothermic preservation injury. Am J Physiol Renal Physiol 286:F838-47
Southard, J H; Knes, J M; Wang, H et al. (2001) Loss of No-induced relaxation in abdominal aorta preserved in a Co-culture system. Transplant Proc 33:855-6
Lindell, S; Nobel, M; Rankin, M et al. (1998) Optimal pH for simple cold storage or machine perfusion of dog kidneys with UW solution. Transpl Int 11:208-11
Hansen, T N; D'Alessandro, A; Southard, J H (1997) Reduced renal vascular injury following warm ischemia and preservation by hypothermic machine perfusion. Transplant Proc 29:3577-9
Hansen, T N; D'Alessandro, A; Southard, J H (1997) Long-term cold ischemia reduces nitric oxide metabolism in reperfused rabbit kidneys. Transplant Proc 29:3417-9
Southard, J H (1997) Improving early graft function: role of preservation. Transplant Proc 29:3510-1
Ametani, M S; D'Alessandro, A M; Southard, J H (1997) The effect of calcium in the UW solution on preservation of the rat liver. Ann Transplant 2:34-8
Stubenitsky, B M; Ametani, M; Danielewicz, R et al. (1995) Regeneration of ATP in kidney slices after warm ischemia and hypothermic preservation. Transpl Int 8:293-7

Showing the most recent 10 out of 29 publications