title: Alpha-1-proteinase inhibitor prolongs small intestinal graft preservation and survival.
abstract: Organ preservation solutions currently used for cold storage of human donor organs are less effective in preserving small intestinal grafts than other organ grafts. The maximal safe period of cold preservation for human small intestinal graft is only about 6 hours. The pathology of preserved and reperfused small intestinal grafts is characterized by mucosal autolysis and sloughing. The authors speculated that the preservation/reperfusion injury results from a proteinase/proteinase-inhibitor imbalance in the graft that favors tissue degradation. This study evaluates whether the addition of an alpha-1-proteinase inhibitor (alpha-1-PI) to the preservation solution can improve graft survival after small bowel transplantation. Forty small intestinal grafts (20 cm long) were harvested from Lewis rats. The grafts were divided randomly into three groups and were preserved in one of the following solutions: normal saline (NS) (n = 10), alpha-1-PI (25 mg/mL; n = 20), or proteinase-free bovine serum albumin (BSA) (25 mg/mL; n = 10). After 12-hour cold storage in the respective solutions, the grafts were transplanted orthotopically into syngeneic recipients. Full-thickness graft biopsies were performed before and 1 hour after revascularization. The effectiveness of preservation was judged by graft histopathology and recipient survival. Histological studies showed that there was less mucosal autolysis and sloughing of the grafts in the alpha-1-Pl group than in the other two groups. All recipients in the NS and BSA groups died of graft failure within 7 days (NS: median, 4 days; range, 2 to 5 days; BSA: median, 6 days; range, 4 to 7). However, 60% (12 of 20) of the recipients in the alpha-1-PI group survived more than 90 days (median, > 90 days; range, 4 to > 90 days; P < .005 v NS or BSA groups, log-rank method). These data suggest that the inclusion of alpha-1-PI in the preservation solution may enhance graft integrity and improve the surgical outcome after small bowel transplantation.
authors.affiliation: Department of Surgery, Indiana University School of Medicine, Indianapolis, USA.
authors.forename: R
authors.initials: R
authors.lastname: Yang
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
authors.forename: M H
authors.initials: MH
authors.lastname: Collins
authors.forename: J L
authors.initials: JL
authors.lastname: Grosfeld
authors.forename: M D
authors.initials: MD
authors.lastname: Pescovitz
mesh_terms: D000818:Animals; D001706:Biopsy; D002417:Cattle; D015925:Cryopreservation; D004353:Drug Evaluation, Preclinical; D006085:Graft Survival; D006801:Humans; D007421:Intestine, Small / Q000201:enzymology / Q000473:pathology / Q000637:transplantation*; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D015842:Serine Proteinase Inhibitors; D013997:Time Factors; D000515:alpha 1-Antitrypsin
chemical_list: D019188:Organ Preservation Solutions; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin