The Usefulness of bowel transplantation and Efficacy of Ciclosporin for bowel transplantation in Rabbits

1991 Fiscal Year Final Research Report Summary

• Project/Area Number: 01570735
• Research Category: Grant-in-Aid for General Scientific Research (C)
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Yamagata University
• Principal Investigator: YAMAGIWA Iwao Yamagata University, School of Medicine Assistant Professor, 医学部, 講師 (60182424)
• Co-Investigator(Kenkyū-buntansha): OBATA Kazuya Yamagata University, School of Medicine Assistant, 医学部, 助手 (10214214)
• Project Period (FY): 1989 – 1990
• Keywords: bowel transplantation / Rabbit / Ciclosporin / tissue pH / tissue PO2

Research Abstract

Bowel transplantation is considered to be the only means of radima treatment for the short bowel syndrome. The present study was designed on the assumption of bowel transplantation in children. In consideration of the size of childriknla intestines, bowel transplantation was. performed in rabbits to establish a model. CSA was used in the management of immunological rejection, and absorption in the transplanted small intestine was tested to evaluate graft function. In addition, preliminary experiments were conducted to produce ischemia in the transplanted intestine and to determine the optimum dose of Ciclosporin. The following results were obtained :
1) After administration of Ciclosporin 10 mg/kg/day i. m., the trough level serum concentration of the drug was maintained at 100-200 ng/ml, suggesting that this ix the optimum does in the rabbit.
2) The TcPO_2 and TcpH in the small intestine of the rabbit were 36.07+__-9.97 mm Hg and 6.94+__-0.15, respectively.
3) As a precondition for trans plantation, ischemia was experimentally produced in the intestine by simultaneous occlusion of the superior mesenteric artery and the portal vein ; The results showed that. both TcPO_2 and TopH were improved if the duration of ischemia was less than 60 minutes.
4) Bowel transplantation with Ciclosporin administration resulted in successful graft survival in 11 of 18 animals(. 61-. 14). When Ciclosporin was discontinued in 4 of the 11 animals, all of th. e 4 grafts were rejecied. since the amount of antigen was small, the rejection in these rabbits took the form of chronic rejection.
5) Histological examination in the rejected graft group revealed gradual flattening of the villi and thickening of the muscle layer, which led to hemorrhagic necrosis. In contrast, the surviving graft group had almost normal structure. Lymph vessels began to be tocanalized within about 2 weeks after transplantation.
6) In absorption tests on the transplanted inthatine, the rejected graft group exhibited reduced glucose absorption on day 2 after transplantation and no absorption on day 7. The change in this group appeared earlier than macroscopic changes in the artificial anus, suggesting the possible usefulness as an Indicator of immunological rejection.
7) The study to determine the optimum length of the intestine to be transplanted could not be conducted due to the large amount of antigen and technical problems.