Effect of pancreatic warm ischemia on islet yield and viability in dogs.

BACKGROUND: Defining tolerable warm ischemia (WI) is mandatory before nonheartbeating cadavers can be used to enlarge the donor pool. No studies to date have precisely evaluated the effect of pancreatic WI on islet yield and viability in a large animal model. METHODS: We used mongrel dogs in our study at the University of Minnesota. Excised pancreases were left in situ for a designated period (0, 30, 45, and 60 min in groups 1 to 4, respectively) of WI. Then, they were digested by the automated collagenase digestion method of Ricordi, purified on Euro-Ficoll discontinuous gradients with the COBE cell processor, and autotransplanted into the liver via a mesenteric vein. We compared the four groups in terms of islet yield, expressed as islet equivalents (IE; diameter standardizing to 150 microm) per pancreas weight (IE/g pancreas), and viability, assessed by functional success (maintenance of normoglycemia for 2 weeks) after transplant. RESULTS: Mean islet yield (+/- SD) and the functional success rate after transplant were as follows: 6200+/-1800 IE/g pancreas and 4 of 4 (100%) in group 1; 6300+/-4400 and 4 of 4 (100%) in group 2; 3800+/-2600 and 2 of 4 (50%) in group 3; and 1400+/-1300 and 0 of 4 (0%) in group 4 (P=0.01 vs. group 1). CONCLUSIONS: With 30 min or less of WI, there are no deleterious effects on islet yield and viability. However, with periods of WI longer than 30 min, the loss in islet yield is severe, resulting in functional failure after autotransplantation. The limit of WI that is tolerable for islets is shorter than for a whole pancreas.

Risk factors associated with surgical site infection and the development of short-term complications in macaques undergoing indwelling vascular access port placement.

BACKGROUND: Risk factors associated with surgical site infection (SSI) and the development of short-term complications in macaques undergoing vascular access port (VAP) placement are evaluated in this study. METHODS: Records from 80 macaques with VAPs were retrospectively reviewed. Logistic regression was used to identify factors associated with short-term post-operative complications. RESULTS: The primary outcome was SSI, which occurred in 21.6% (52.6% in the first 12 months vs. 13% thereafter) of procedures. SSI was associated with major secondary complications including VAP removal (11.4%), wound dehiscence (5.7%), and mechanical catheter occlusion (5.7%). In multivariate modeling, only surgical program progress was a statistically significant predictor of SSI, while animal compliance had a slightly protective effect. CONCLUSIONS: Vascular access ports have a moderate risk of complications, provided the surgical program optimizes best practices. Under complex experimental conditions, VAPs represent an important refinement, both improving animals' overall well-being and environment and reducing stress.

Total lymphoid irradiation, without intrathymic injection of donor cells, induces indefinite acceptance of heart but not islet or skin allografts in rats.

Allograft tolerance occurs in rodents given a dose of antilymphocyte serum (ALS) and intrathymic injection (ITI) of donor splenocytes (SC) 1-3 weeks prior to transplant (TX). The purpose of our study was to test total lymphoid irradiation (TLI) as an alternative to ALS in ITI tolerance induction to heart, islet, and skin allografts. Prepubertal Wistar Furth rats were recipients. ITI of donor (Lewis) SC was done at the end of the TLI course. Rats received either a heterotopic heart, a skin graft, or 2300 islets (diabetic recipients) intraportally from Lewis donors. TLI (without ITI) in a dose of 200 rads/day for 5 consecutive days, followed by TX in 3 weeks resulted in indefinite acceptance of heart (but not islet or skin) grafts in 60% of the recipients. These data indicate that TLI by a dose schedule of 200 rads/day for 5 days should be tested for clinical relevance in large animal recipients of immediately vascularized grafts.