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Pathogesis and prevention of graft rejection and graft coronary arteriosclerosis in an experimental heart transplantation model

Research Project

Project/Area Number 03670651
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Thoracic surgery
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

TABAYASHI Koichi  Tohoku University School of Medicine, Department of Thoracic and Cardiovascular Surgery Lecturer, 医学部・附属病院, 講師 (90142942)

Co-Investigator(Kenkyū-buntansha) OHMI Mikio  Tohoku University School of Medicine, Department of Thoracic and Cardiovascular, 医学部・附属病院, 講師 (00144931)
Project Period (FY) 1991 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1992: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1991: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordsworking model / non-working model / coronary arteriosclerosis / graft rejection / graft coronary arteriosclerosis / workingモデル / 急性拒絶反応 / 慢性拒絶反応 / PGI_2 / non-working model / working model / 冠動脈病変 / 心臓移植 / 冠動脈硬化 / シクロスポリン / FK506 / 15ーDeoxyspergualin
Research Abstract

The purpose of this study are to evaluate the effects of immunosuppressivedrugs, to compare the effects of non-working left heart model and working model, and to assess the protective effects of PG12 on myocardial rejection and coronary arteriosclerosis after heterotopic heart transplantation.
1)Comparison of the effects of Cyclosporine(Cs), FK-506(FK) and 15-Deoxyspergualin(DOS) on coronary arteriosclerosis after rat heart transplantation.
Three gruops of Lewis rats(n=7, each)received heterotopic heart transplants from F-344 donors and were treated with Cs, FK, and DOS intraperitoneally.
All rats were sacrificed 60 days after transplantation and assessed microscopic grading asore of rejection and arteriosclerosis, andmeasured serum lipid.
There was no significant difference in the grading score of arteriosclerosis in the Cs group was significantly higher than it of DOS group.
Trigriceride level in the Cs group was significantly higher than the FK and DOS groups, and LOL level in the Cs and … More FK groups were significantly higher than them of DOS group. We conclude that DOS has a superior protective effect against coronary arteriosclerosis after heart transplantation and it may depend on the different mechanizm of immunosuppression and lipid metabolism abnormality causing by immunosuppressants.
2)Technique for working left heart model of heterotopic(abdominal)heart transplantation.
The interatrial septum and tricuspid valve of the donor heart are removed. The pulmonary arterial trunk, pulmonary veins, and inferior vena cava are ligated, and the stumps of the donor aorta and superior vena cava are anastomosed in an end-to-side fashion to the recipient abdominal aorta and inferior vena cava, respectively. In this model, the donor left ventricle did not pump out enough venous blood to desaturate the recipient femoral arterial blood but did generate approximately the same pressure as the recipient's heart.
3)Comparison of the effects of non-working left heart model and working model, and the protection effects of prostaglandin 12(PG12) on graft rejection and graft coronary arterisclerosis after heterotopic heart transplantation.
Fischer rats were used as donors and Lewis rats as recipients.
Twenty Fischer to Lewis allograft were diveded equally into six groups.
Group 1 received working type of heterotopic heart transplantation without treatment of cychosporin A (Cy A) and PG12, and killed on day 20.
Group 2 received non-working type of heterotopic heart transplantation without treatment of Cy A and PG12, and killed on day 20.
Group 3 received working type of heterotopic heart transplantation with treatment of CY a and without PG12, and killed on day 60.
Group 4 received non-working type of heterotopic heart transplantation with treatment of Cy a and without PG12, and killed on day 60.
Group 5 received working type of heterotopic heart transplantation with treatment of Cy A and PG12, and killed on day 60.
Group 6 received non-working type of heterotopic heart transplantation with treatment of Cy A and PG12, and killed on day 60.
The severity of rejection was evaluated using Billingham grading scale.
The degree of coronary arterial injury was assessed using Lurie grading scale.
Left ventricular wall theckness was measured at the free wall and interventricular septum. The following results were obtained.
i)LV free wall thickness of graft in working model was significantly thicker than it in recipient heart.
LV wall thickness of grafts in non-working model was the same as it in recipient heart.
ii)The degree of rejection in working model was the same as it in non-working model.
iii)The degree of coronary arterial injury in working model was significantly lesser than it in non-working model.
iv)There was no significant difference of the degree of rejection with or without treatment of PG12.
v)There was no significant difference of the degree of graft coronary arteriosclerosis with or without treatment of PG12. Less

Report

(4 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • 1991 Annual Research Report
  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] Ohmi M,Yokoyama H,Nakame T,et al: "Hemodynamic performance in a heteropically transplanted dog heart:Roposal of techniques for working left heart model of heterotopic(abdominal)heart transplantation." J.Heart.Lung.Transplant.11. 1147-1150 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohmi M,Yokoyama H,Nakame T,et al: "Hemodynamic performance in a heterotopically transplanted dog heart:Roposal of techniques for working left heart model of heterotopic(abdominal)heart transplantation." J.Heart.Lung.Transplant.11. 1147-1150 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ohmi M, Yokoyama II,Nakame T. et al: "Hemodynamic performance in a heterotopically transplanted Dog heart: Proposal of techniques for working left heart model of he terotopic(abdominal) heart transplantation" J Heart Lung transplant. 11. 1147-1150 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 長嶺 進: "心移植後の冠動脈硬化に関する実験的研究ー特に免疫抑制剤の影響についてー" 日本胸部外科学会雑誌.

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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