Long-Term Study of Vascularized Free-Draining Intraperitoneal Pancreatic Segmental Allografts in Beagle Dogs

Abstract

A B S T R A C T The purpose of the present study was to evaluate the significance of immunogenetic factors on the survival of pancreatic allografts in beagle dogs. Donors and recipients were leukocyte antigen (DLA)-typed and mixed lymphocyte culture (MLC)-tested. Recipients were made diabetic by total pancreatectomy and immediately implanted intraperitoneally with a vascularized, free-draining (duct unligated) pancreatic segmental (FDPS) allograft. Two groups of dogs were studied. In group I consisting of donor-recipient littermates, recipients were immunosuppressed with prednisone and azathioprine (n = 16 dogs), or not immunosuppressed (n = 4). In group II, recipients were made specifically unresponsive by total body radiation, autologous marrow implantation, and kidney transplantation from DLA-MLC identical donors, 1 yr before FDPS transplantation from the corresponding original kidney donors.Survival of the FDPS grafts in group I was inversely related to pretransplant MLC reactivity, irrespective of DLA genotyped match between donor and recipient. Thus, immunosuppressed high MLC reactors (n = 8) rejected FDPS grafts between 7 and 14 d, whereas immunosuppressed low MLC reactors (n = 8) accepted grafts for 25 to 260+ days, and nonimmunosuppressed low MLC reactors (n = 4) accepted grafts for 9-55 d. Rejection (hyperglycemia) of FDPS grafts was sudden, permanent, and unpredictable despite weekly intravenous glucose tolerance tests with measurements of glucose disappearance rates and serum insulin responses. Nevertheless, serial in vitro cell-mediated

Pancreas and islet transplantation

“…However, insulin levels then declined as hyperglycaemia occurred. In contrast, Kyriakides et al [58] found that changes in glucose clearance during glucose tolerance tests or in serum insulin response did not precede rejection, and that the occurrence of hyperglycaemia was rapid and unpredictable. They were, however, able to demonstrate changes in cell mediated lymphocytotoxicity .against the donors before overt rejection.…”

“…Blood glucose and insulin levels during glucose or tolbutamide tolerance tests have been variously reportedly as low, normal or elevated [9,17,18,24,28,34,36,40,[53][54][55][56][57][58]. The factors responsible for the different results are difficult to sort out because of the variations in the models studied.…”

“…Pancreatic allografts are subject to rejection just like any other organ [18,20,26,27,37,40,44,[58][59][60][61][62][63]. The functional criteria used to define rejection differ for various organs and may make it appear that the pancreas is more or less susceptible to rejection than another organ [9]~ but in experiments with en bloc allotransplantation of the pancreas, duodenum, liver, spleen and kidney in rats, histological evidence of rejection was seen in all organs either simultaneously or within a few days of each other [26].…”

“…Verschoor et al [40] reported that the median survival time of pancreatic grafts in nonimmunosuppressed partially matched beagles was 9 days, while in dogs immunosuppressed with azathioprine it was 27 days and with ALS it was 51 days. Kyriakides et al [58] found that the duration of pancreas graft survival in beagles correlated most strongly with the recipients' reactivity in mixed lymphocyte culture (MLC) to the donor. In MLC reactive recipients immunosuppressed with azathioprine and prednisone, graft survival ranged from 25 to 260 days.…”

Experimental vascularized segmentai pancreatic and islet transplantation in the baboon

“…The technique of transplantation has previously been described [11]. Briefly, the tail of the pancreas was implanted heterotopically in the peritoneal cavity with the duct unligated and opening intraperitoneally [12]. End-to-side arterial anastomosis between the proximal splenic artery and the aorta, and endto-side venous anastomosis between the splenic vein and inferior vena cava was carried out, thus establishing venous drainage of the pancreas into the systemic circulation.…”