Acinar structure and function in canine pancreatic autografts with duct drainage into the urinary bladder.

Abstract

Autotransplants of pancreas in 8 dogs, with exocrine drainage into the urinary bladder, were stimulated in vivo with cholecystokinin-pancreozymin (CCK-PZ). Transplant biopsies, when compared with 6 normal pancreases, showed normal acinar structure by light and electron microscopy 13-18 months after initial surgery; 2 transplants with sutures unintentionally transecting ducts were fibrosed and had duct obstruction. After in vivo stimulation, the normal-appearing transplants produced a 7-fold increase in urinary amylase, and quantitative electron microscopy showed a 50% reduction in mature zymogen granules; there were no intracellular organelle abnormalities prior or subsequent to stimulation. Fibrosed transplants produced lesser urinary amylase both prior to and after stimulation. In vitro stimulation of grafts with normal structure increased amylase secretion from 1.5-2.1-fold. In vitro dose-response showed a maximum at 10(-9)M cholecystokinin-octopeptide (CCK-OP) in transplant and control. The in vivo stimulation is more responsive and may be useful for clinical monitoring of graft survival. In vivo stimulation occurred after induced urinary tract infection; because no pancreatitis ensued, a regimen of trophic stimulation by CCK-PZ was not contraindicated. The bladder tolerated exocrine drainage with no significant change, and bladder infection did not adversely affect the transplant. The islets appeared normal in the transplants by light and qualitative electron microscopic observation; fasting blood glucose and insulin values were normal during the 12-18-month follow-up. Bladder drainage of segmental grafts of pancreas provides a preparation with intact acinar-islet relationships; the present observations suggest that this may permit longer islet survival in the absence of acinar destruction and subsequent fibrosis.