ISLET-CELL HORMONE-RELEASE IMMEDIATELY AFTER HUMAN PANCREATIC TRANSPLANTATION - A MARKER OF TISSUE-DAMAGE ASSOCIATED WITH COLD ISCHEMIA

Pancreatic graft procurement, preservation, and transplantation surger y may result in damage to and loss of the integrity of endocrine cells and consequently in leakage of cell products into the insular vascula r capillaries. Thus, the amount of alpha-, beta-, and pancreatic polyp eptide (PP) cell products released into the vascular space of the reci pient immediately after graft reperfusion may reflect islet cell injur y. To test this hypothesis, we assessed glucagon, PP, C-peptide, and i nsulin levels in a prospective study of 22 consecutive renal-pancreati c transplantations. Transplantation-related parameters were used to ac count for differences in hormone release. Five grafts were preserved u sing Euro-Collins preservation fluid and 17 grafts were preserved usin g University of Wisconsin solution (UW). The first sign of a reinstall ed physiological axis was the decrease of the blood glucose concentrat ion after a median duration of 40 min (range 5-90 min) and the associa tion of the recipient's ambient blood glucose levels with insulin rele ase between 25 and 180 min after reperfusion. The delay period before a fall in blood glucose was observed correlated with cold ischemia tim e (r(s)=0.73, P<0.001, n=21). An immediate and marked increase in plas ma levels of glucagon (from 180+/-18 to 585+/-99 ng/L, mean +/- SEM), PP (from 57+/-8 to 122+/-13 pmol/L), C-peptide (from <0.06+/-0.02 to 5 .43+/-0.63 nmol/L), and insulin (from 0.15+/-0.21 to 2.05+/-0.26 nmol/ L) was observed. C-peptide release correlated with glucagon (r=0.76, P <0.001) and PP (r=0.60, P<0.01). The hormone release was compared with computed tomography scans that were performed in the immediate postop erative period in 15 UW-preserved allografts. The diameter of the panc reatic head was increased and ranged from 4.5 to 7.7 cm (mean 6.2 cm). Peroperative C-peptide release significantly correlated with morpholo gical graft changes reflected by the pancreatic head diameter (r=0.58, P=0.02). In a stepwise multiple regression analysis, cold ischemia ti me was a significant factor for the release of PP (r(2)=0.18, P=0.049) and C-peptide (r(2)=0.35, P=0.004). We suggest that peroperative horm one release reflects endocrine tissue damage. Furthermore, cold ischem ia time may jeopardize the pancreatic allograft after relatively short preservation times, even when UW is used.