1993 Fiscal Year Final Research Report Summary
Anastomotic remodeling after multiple organ transplantation
| Project/Area Number |
03670607
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | UNIVERSITY OF TOKYO |
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Principal Investigator |
SHIGEMATSU Hiroshi University of Tokyo Surgery, Lecturer, 医学部・附属病院, 助手 (40134556)
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| Co-Investigator(Kenkyū-buntansha) |
ARAMOTO Haruo University of Tokyo Surgery, Assistant, 医学部・附属病院, 医員
HATAKEYAMA Takuya University of Tokyo Surgery, Assistant, 医学部・附属病院, 医員
NUNOKAWA Masao University of Tokyo Surgery, Assistant, 医学部・附属病院, 医員
OHSHIRO Hidemi University of Tokyo Surgery, Assistant, 医学部・附属病院, 医員
YASUHARA Hiroshi University of Tokyo Surgery, Lecturer, 医学部・附属病院, 助手 (50251252)
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| Project Period (FY) |
1991 – 1993
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| Keywords | multiple organ transplantation / vascular anastomosis / anastomotie intimal hyperplasia / FK506 / tissue preservation / microcirculation / reperfusion injury / PDGF |
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| Research Abstract |
Immunologic mechanisms also have been implicated in the development of pseudointimal hyperplasia which is the major cause of occlusion following vascular surgery using artificial prosthetic grafts in the late postoperative stages.
In this study, we implanted cPTFE grafts into abdominal aortae of dogs by end to end proximal anastomosisand by end to side distal anastomosis. The dogs were then devided into three groups, control group A,group B treated with low dose (0.1mg/kg/week) of FK506 and group C with high dose (0.2mg/kg/week). The first dise was given at the seventh day after surgery and subseaquent weekly injection continued for 6 months. At sixth month, the arotaewas harvested, fixed, longitudinary sectioned and the average width of pseudointima was determined. As compared to control group A,FK506 caused significant reduction in psuedointimal thickness at the proximal and the distal toe side anastomosis in the Group B and C.However, the suppression of pseudointima at the distal hee
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l anastomosis was not significant. These data show that an inhibitory effects of FK506 on pseudointimal hyperplasia following vascular anastomosis has the difference in the site of anastomosis and further suggest the involvement of immunological regulation in the intimal hyperplastic response.
Then, in order to study the efficacy of FK506 on suppression of intimal thickness and to determine the immunohistological effects of FK506, we implanted ePTFE grafts into abdominal aortac of New Zealand White rabbits in the same way as that of dogs above-mentioned, and the rabbits were receiving a 1% choresterol diet 2 weeks before and for 8 weeks after operation and ramdomly devided into three groups, control group D,group E treated with placebo ointment and group F treated with 1% FK506 ointment. Eight weeks later, each entire graft was harvested including the adjacent aortae, longitudinally sectioned and the width of anastomotic pseudointima was determined. The change in the serum cholesterol level was similar among these three groups. Whole blood concentration of FK506 faded away by 5 weeks after surgery. As compared to group D and group E,FK506 ointment caused significant reduction in psuedointimal thickness at every anastomotic sites in group F.These data show that local treatment administration of FK506 ointment, as well as systemic administration, inhibits the pseudointimal hyperplasia following vascular anastomosis. Less
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