The objective of this study is to develop a preservation solution for the pancreas that is optimal for 72 hour preservation but additionally is equally effective for the preservation of other organs, including the kidney, liver, heart, and heart-lung. This development will make a single preservation solution available for transplant surgeons to use for all intra-abdominal organs. The preservation solution will be developed by studying how modifications of a recently developed cold storage solution (UW solution) affects preservation quality of the pancreas as judged in the autotransplant canine model of segmental pancreatic transplantation. This study will be solely funded by this grant. Concurrently, studies will continue to further improve preservation of the kidney and liver (other NIH funded grants). Changes in the preservation solution or method that appear to improve the quality of one organ will be tested in the other groups. This method will allow development of a single preservation solution and also determine if there are universal principles applicable to the preservation of different organs. In this study pancreases_will be preserved for 72 hours and quality assessed by transplantation and determination of blood glucose, insulin, c-peptide, intravenous glucose tolerance test, serum amylase, and histochemical and pathological examination of the transplanted pancreas. The modification of the UW solution to be tested include determining: i) the role of the colloid, hydroxyethylstarch, in preservation, ii) preservation efficacy in a high sodium medium rather than a high potassium medium, and the appropriate concentrations of these electrolytes necessary for optimal function, iii) the ideal storage pH and hydrogen ion buffer, iv) the concentrations of calcium necessary for optimal preservation, and v) how drugs affect preservation quality including antioxidants and oxygen free radical scavengers. This study ill make available a preservation solution effective for relatively long-term storage of intra-abdominal organs, make the solution available for worldwide distribution, facilitate multiple organ harvest from a single donor, and provide valuable information on the mechanisms of action of cold storage solutions in organ preservation. The solutions developed will be tested in clinical pancreas preservation and transplantation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK033554-04A1
Application #
3231977
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1984-12-01
Project End
1992-04-30
Budget Start
1989-05-01
Budget End
1990-04-30
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Southard, J H; van Gulik, T M; Ametani, M S et al. (1990) Important components of the UW solution. Transplantation 49:251-7
Wahlberg, J; Southard, J H; Belzer, F O (1989) Preservation-induced pancreatitis in an isolated perfused pancreas model in the dog. Transpl Int 2:165-7