Pancreas Autotransplantation in Pig With Systemic or Portal Venous Drainage

Abstract

The effect of the type of venous drainage of the graft on its endocrine function was studied in two groups of pigs after segmental pancrease autotransplantation. Group 1 comprised 10 pigs with portal venous drainage (PVD) and group 2 comprised 10 pigs with systemic venous drainage (SVD). The graft consisted of body and tail of the pancreas. The pigs were totally pancreatectomized. The pancreatic duct was occluded by neoprene injected into the duct. One week before and 1 and 3 months after transplantation, intravenous glucose tolerance (IVGTT) and meal stimulation tests (MST) were performed. Plasma glucose (PG), insulin (INS), C-peptide, glucagon (GLU),and pancreatic polypeptide (PP) were measured during the tests. All pigs had normal fasting PG, 1 and 3 months after PanTx, although MST disclosed significantly higher PG (P<0.05) during the test after transplantation. In the PVD group, a decrease in INS level during both test was recorded after PanTx (P<0.05), while in the SVD group a nonsignificant rise in INS level was recorded compared with before transplant. A significant difference (P<0.05) in INS levels were present both 1 and 3 mon. after PanTx between the two groups. Pigs with PVD showed a higher (P<0.05) C-peptide level than pigs with SVD during IVGTT. The initial significant rise in PP during MST and the initial fall in PP during IVGTT recorded in all pigs before transplantation were totally lost after transplantation in both groups. During the tests, PP remained steady and significantly lower than the pretransplantation levels in both groups. A significantly higher GLU level during both IVGTT and MST was observed in SVD compared with PVD 1 month after PanTx (P<0.05), being more pronounced during MST. This accentuated GLU concentration decreased by 3 months after transplantation, although it was still significantly greater than pretransplantation levels. We concluded that the unnatural mode of delivery of pancreas endocrine secretion to systemic rather than to portal circulation leads to derangements in pancreatic endocrine function in order to maintain glucose homeostasis. This may cause earlier exhaustion of islet cells. Segmental rather than whole organ and duct occlusion rather than exocrine drainage may further contribute to this, shortening the effective life of the graft.

Physiologic and metabolic results of pancreatic cold storage with Histidine-Tryptophan-Ketoglutarate-HTK solution (Custodiol)® in the porcine autotransplantation model

“…In the clinical setting, the intraperitonea1 absorption of secretions (according to the surgical model) but also the preservation time is responsible for this phenomenon. Abnormalities of the insuline secretion and the glucose homeostasis are known in this model (but also in humans) using systemic venous drainage as compared with the portal venous drainage [22,9,5,171. This has been attributed to several factors such as the suboptimal mass of transplanted p-cells [9], the effect of denervation [l], and the effect of the systemic diversion of the hormon bypassing the hepatic clearance [4].…”

“…This has been attributed to several factors such as the suboptimal mass of transplanted p-cells [9], the effect of denervation [l], and the effect of the systemic diversion of the hormon bypassing the hepatic clearance [4]. However, this phenomenon may occur late and after several months, resulting in early exhaustion of islet cells and progressive graft fibrosis [22,29]. In the clinical setting, DEGF has been correlated to recipient-related factors such as obesity, donor age, and cardiocerebrovascular causes of donor death, rather than to the preservation time [26].…”

Functional and structural integrity of porcine pancreatic grafts subjected to a period of warm ischemia and cold preservation with histidine-tryptophan-ketoglutarate (custodiol) or University of Wisconsin solution

“…These results were confirmed in the present model, and no differences in peak insulin levels between the two solutions were encountered. Persistent postoperative hyperinsulinemia is a well-known problem in pancreas transplantation (22,23). This abnormality has been attributed to several factors such as the suboptimal mass of transplanted ␤ cells, the effects of denervation, or the systemic diversion of hormone bypassing hepatic clearance (24,25).…”

A Simplified Technique of Pancreas Transplantation in a Porcine Model

“…SVD has been the most commonly used surgical technique so far. However, clinical trials as well as animal experiments have shown that SVD can result in nonphysiological hyperinsulinemia and hyperglucagonemia [22,24,25,26]. Using PVD, a more physiological insulin delivery is achieved, which prevents hyperinsulinemia and improves lipoprotein composition [24,25,26].…”

“…It had been believed that the simultaneous transplantation of the duodenum is not necessary for the adequate function of the transplanted pancreas, and the inclusion of the duodenum and its rejection might complicate clinical attempts of transplantation [31]. In spite of this belief, the exocrine pancreas reconstruction has been shown as a necessity in some studies [25,32]. There are three types of exocrine drainage, including bladder drainage, enteric drainage and gallbladder drainage.…”