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

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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