epidermal-growth-factor and bactenecin

Serum-free preservation media such as University of Wisconsin (UW) may cause tissue damage through trophic factor (TF) deprivation. This study evaluated whether the addition of TFs to UW solution improves liver graft quality after extended cold preservation time in pigs. UW solution was supplemented with epidermal growth factor, insulin-like growth factor-1, nerve growth factor-beta, bactenecin, and substance P to create TF-supplemented (TFS) UW. Orthotopic liver transplantation was performed after 18 hr of static cold storage at 4 degrees C in UW (n=7) or TFS-UW (n=7) solution. Recipients of grafts preserved with TFS-UW demonstrated significantly better 5-day survival (57%) than those preserved with UW alone (14%) (P<0.05). Adenosine triphosphate content in grafts preserved in TFS-UW was significantly higher than in grafts preserved in UW (17.4+/-5.0 vs. 4.8+/-1.2 nmol/mg protein, respectively) (P<0.05). This study showed that the addition of TFs to UW solution allowed a significant extension of cold ischemic time in pigs.

Topics: Adenosine; Allopurinol; Animals; Epidermal Growth Factor; Glutathione; Graft Survival; Growth Substances; Insulin; Insulin-Like Growth Factor I; Liver; Liver Transplantation; Models, Animal; Nerve Growth Factor; Organ Preservation Solutions; Peptides, Cyclic; Raffinose; Substance P; Swine

This study examined the effect of trophic factor supplementation [TFS; bovine neutrophil peptide-1 (bactenecin), 1 mg/L; substance P, 2.5 mg/L; nerve growth factor, 20 microg/L; epidermal growth factor, 10 microg/L; insulin-like growth factor-1, 10 microg/L] during cold storage with UW lactobionate solution. Dogs transplanted with kidneys stored for 4days in TFS-UW had significantly lower peak serum creatinine values (mean 2.9 +/- 0.2mg/dL) and returned to normal values faster (6 days) than kidneys stored for 3days in unmodified UW solution (4.2 +/- 0.3 mg/dL and 14 days, respectively). Kidneys stored for 5days in TFS-UW (mean peak creatinine 3.7 +/- 0.3) functioned equivalently to kidneys stored for 3days and better than kidneys stored for 4 days in UW alone. Dogs with kidneys stored for 6days in TFS-UW had mean peak creatinines of 5.7 +/- 0.4 mg/dL. These returned to normal creatinine values in 14 days, equal to 3-day stored and significantly better than kidneys stored for 4days in UW alone (20days recovery time). This study shows trophic factor deprivation appears to be a critical mechanism of injury in organ preservation with current synthetic storage media, and marks the initial development of a synthetic biologically active preservation solution, the next generation of preservation media.

Topics: Adenosine; Allopurinol; Animals; Cold Temperature; Dogs; Epidermal Growth Factor; Female; Glutathione; Insulin; Insulin-Like Growth Factor I; Kidney; Male; Nerve Growth Factor; Organ Preservation; Organ Preservation Solutions; Peptides, Cyclic; Raffinose; Substance P