First brain dead donor heart transplantation under new legislation in Japan.

The first heart transplantation was carried out in Japan successfully, after the brain death and organ transplantation law was settled in 1997. The recipient patient was a 47-year-old man with the dilated phase of hypertrophic cardiomyopathy who had been on a Novacor implantable left ventricular assist system for the previous 4 months. Since the donor hospital was about 200 km from the recipient hospital which took approximately 2 hours for transportation, the total ischemic time was 3 hours and 24 minutes.

Prolonged discordant xenograft survival and delayed xenograft rejection in a pig-to-baboon orthotopic cardiac xenograft model.

Objective: Our objectives were to study delayed xenograft rejection and the effectiveness of pretransplantation total lymphoid irradiation combined with immunosuppression on rejection in a pig-to-baboon cardiac xenograft model.

Methods: Baboons were treated with pretransplantation total lymphoid irradiation, cyclosporine A (INN: ciclosporin), and methotrexate. Orthotopic pig-to-baboon cardiac transplantations were performed after depletion of circulating xenoreactive natural antibody by pretransplantation donor organ hemoperfusion.

Prolonged discordant cardiac xenograft survival in newborn recipients.

Background: We previously demonstrated very low levels of xenoreactive natural antibodies in newborns, suggesting the possibility of prolongation of xenograft survival in newborn recipients. We used a pig-to-newborn goat heterotopic cardiac xenograft model to examine our hypothesis that hyperacute rejection would be absent in newborn recipients and that both humoral and cellular rejection would participate in the late phase of discordant xenograft rejection.

Methods And Results: The serum of newborn goats was found to have very low titers of natural anti-pig antibodies.

Evidence that graft coronary arteriosclerosis begins in the early phase after transplantation and progresses without chronic immunoreaction. Histopathological analysis using a retransplantation model.

The histopathological features of chronic rejection and its initiation were assessed using rat heterotopic heart transplantation and retransplantation models. Fully allogeneic or minor, non-MHC antigen-mismatch heart grafts transplanted into recipient rats treated with a short course of FK506 showed long-term survival but developed graft atherosclerosis after 40 days posttransplantation. Retransplantation of allografts back into the original donor strain did not prevent graft atherosclerosis if the grafts had resided in the primary recipient for up to 5 days; residence in the primary allogeneic recipient for less than 4 days did not result in graft atherosclerosis in the secondary recipient.

Study of efficacies of leukocyte-depleted terminal blood cardioplegia in 24-hour preserved hearts.

To evaluate the effect of leukocyte-depleted terminal blood cardioplegia on prolonged preservation, 41 canine hearts were stored in modified Collins' solution and transplanted heterotopically. Hearts were transplanted soon after harvesting in group 1 and after 24-hour preservation in groups 2, 3, and 4. Blood cardioplegia was applied just before aortic unclamping in groups 3 and 4; group 3 received simple blood cardioplegia and group 4 received leukocyte-depleted cardioplegia.

Effects of transfected complement regulatory proteins, MCP, DAF, and MCP/DAE hybrid, on complement-mediated swine endothelial cell lysis.

We established several swine endothelial cell (SEC) lines, expressing human MCP (CD46), DAF (CD55), and MCP/DAF hybrid by transfection of cDNA, and assessed the function of these transfectant molecules on complement-mediated cell lysis as an in vitro hyperacute rejection model of swine to human discordant xenograft. Discordant organ xenografts are hyperacutely rejected by complement activation. Amelioration of complement-mediated lysis by these transfectant molecules was tested in each SEC line by lactate dehydrogenase assay.

Analysis of rejection mechanism in the rat to mouse cardiac xenotransplantation. Role and characteristics of anti-endothelial cell antibodies.

Recent reports have demonstrated that humoral factors, especially antibodies elicited by xenoantigens, play an important role in the rejection of concordant cardiac xenografts. These induced antibodies, however, have not been well characterized. Therefore, we investigated the rejection mechanism, especially the role of humoral immunological responses in the concordant rat to mouse cardiac xenograft model.

[Aortic valve replacement in a kidney transplant recipient].

A 62-year-old man with chronic renal failure, who had been treated with hemodialysis, received a kidney transplant from his son in December 1989. He kept good renal function without any episode of graft rejection under the immunosuppressive therapy with Cyclosporine A (CyA), Predonine (PRD), and Mizoribine. In 1990 he started to have exertional dyspnea, and was diagnosed to have aortic valve regurgitation.

Role of CD4+ T cells in the rat to mouse cardiac xenotransplantation.

T cell subsets involved in rejection of xenografts were analyzed using a rat to mouse cardiac xenotransplant model. Proliferating response and interleulin-2 (IL-2) production in recipients' spleen cells were almost completely abrogated by elimination of L3T4+ T cells, but not by elimination of Lyt2.1+ T cells.

Test for ability of decay-accelerating factor (DAF, CD55) and CD59 to alleviate complement-mediated damage of xeno-erythrocytes.

We investigated the susceptibility to human complement (C) of xeno-erythrocytes into which phosphatidylinositol (PI)-anchored human C regulatory protein, decay-accelerating factor (DAF) or CD59 had been incorporated. Erythrocytes of sheep (Esh), swine (Esw), dog (Edg), and guinea pig (Egp), unsensitized with human natural antibody (Ab), were used as xeno-target. C-mediated lysis of erythrocytes (E) was induced in both classical and alternative pathways in parallel with the density of the sensitized Ab, except for Egp.

Prolonging discordant xenograft survival with anticomplement reagents K76COOH and FUT175.

The guinea pig heart, when transplanted into the rat heterotopically, is rejected within 30 min via activation of the alternative complement pathway. Natural antibody does not contribute to rejection. This xenotransplantation model was used to assess the effect of anti-complement reagents on discordant xenograft survival.

Effects of terminal cardioplegia with leukocyte-depleted blood on heart grafts preserved for 24 hours.

Canine hearts immersed in modified Collins solution were transplanted heterotopically (n = 23) and orthotopically (n = 15) to evaluate the effect of terminal warm-blood cardioplegia with or without leukocyte depletion. As the index for graft function, preload recruitable stroke work was measured in both series before harvesting (control) and after transplantation (percentage). The heterotopic hearts were divided into four groups (group 1 to 4) according to the preservation method; hearts were preserved for 3 hours in group 1 and for 24 hours in groups 2, 3, and 4.