ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Current lung preservation consists of flushing of the donor organs, with successive hypothermic storage in an inflated state. Recently, hypothermic storage alone was reported to be superior in terms of functional recovery. This study was designed to investigate the metabolic, morphologic, and functional consequences of hypothermic storage alone, in experimental lung preservation.Methods.Orthotopic left-sided lung transplantation was performed in pigs. Donor lungs were flushed with Euro-Collins solution (n=6) or simply explanted (n=6) and stored for 18 hr at 4°C. After this, left-sided single lung transplantation was performed. Sham-operated animals (n=6) served as control. Morphology and metabolism were analyzed in normal lungs, after ischemia and at the end of reperfusion. Gas exchange and pulmonary hemodynamics of the transplanted organs were measured, after exclusion of the native lung from perfusion and ventilation.Results.Metabolic and morphologic evaluation did not show a significant difference between the groups at the end of ischemia. Lungs preserved by hypothermia alone showed a functional recovery close to shamoperated animals and superior to flushed organs.Conclusions.Hypothermia alone is a sufficient means of preservation for explanted lungs for at least 18 hr.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.It is commonly believed that abnormal blood glucose levels indicate irreversible rejection. We were interested in determining the stage at which rejection remains reversible.Methods.A total of 54 Lewis rats were rendered diabetic with 55 mg/kg streptozocin and were then given a pancreas transplant from Brown Norway donors. Pancreatic juice was collected in a subcutaneous reservoir. All recipients received 15 mg/kg cyclosporine A (CsA) for 5 days. CsA was then discontinued for 2 days (n=7, group 1), 4 days (n=7, group 2), 6 days (n=9, group 3), 8 days (n=9, group 4), 9 days (n=11, group 5), and 10 days (n=11, group 6). Two animals of each group were euthanized at the end of the immunosuppressive-free interval, for histological assessment of the grade of rejection (GO, GI, GII, GIII). Rejection was treated with methylprednisolone (7 mg/kg body weight) and CsA (15 mg/kg body weight). The volume of pancreatic juice, together with juice cytology (CO, CI, CII) and blood glucose levels, was assessed daily.Results.Blood glucose remained normal throughout the observation period in animals with GI and GII rejection. The numbers of animals that became diabetic were as follows: 5 of 9 (group 4), 7 of 11 (group 5), and 8 of 11 (group 6). Decreased amounts of pancreatic juice were observed in all animals, except those in group 1. The histology returned to normal after anti-rejection therapy in four animals (57%) of group 1, in two animals (28%) of group 2, and in one animal (11%) of groups 3 and 4, respectively. Although there was no animal in groups 5 and 6 with normal graft histology after treatment, there were still four (36%) and three (27%) animals, respectively, that were normoglycemic and that had pancreatic grafts with well-preserved islets.Conclusions.From these data, we conclude that even GIII rejection with severe endothelialitis and isleitis can be reversed. Therefore, we suggest that a trial of enhanced immunosuppression is justified in patients with advanced pancreas allograft rejection.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The aim of this study was to analyze the possible protective effects of a glutamine and arginine precursor (ornithine-α-ketoglutarate [OKG]) on the mucosa of a transplanted intestine when administered with either a defined formula oral diet (DFD) or a standard chow. Isogenic male Lewis rats (250 g) were submitted to a laparotomy (groups 1 and 2) or to an orthotopic small bowel transplantation (SBT; groups 3-6). Groups 1, 3, and 5 received a DFD 14 days after surgery. Groups 2, 4, and 6 received standard chow. In addition, groups 5 and 6 received a daily oral supplementation of 1.4 g/kg of OKG. Weight changes and food intake were recorded daily. At the end of the study, bacterial translocation (BT) was measured in mesenteric lymph nodes, liver, and spleen. The protein/DNA index was also determined in intestinal mucosa. SBT induced BT in all transplanted groups, especially in those fed DFD. Addition of OKG (groups 5 and 6) significantly reduced BT in comparison with groups 3 and 4 and improved the protein/DNA index as well as weight gain. It is concluded that OKG supplementation protects the intestinal barrier after SBT, and that this effect is more marked when it is added to a standard chow.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Transplantation of discordant xenograft tissues usually results in antibody-mediated hyperacute rejection response. It has been speculated that because cartilage has a limited vascular, neural, and lymphatic supply, it might be immunologically privileged and may not undergo hyperacute or chronic rejection. Moreover, porcine and bovine cartilage were found to express very low amounts of α-galactosyl epitopes (Galα1-3Galβ1-4GlcNac-R). To evaluate animal cartilage for possible human transplantation, xenograft meniscal cartilage was transplanted from pigs and cows into the suprapatellar pouches of six cynomolgus monkeys (group 1). In a second group of six monkeys (group 2), porcine meniscal cartilage and porcine articular cartilage plugs were evaluated. During the 2-month evaluation period in group 1, all monkeys displayed an extensive humoral response to the xenograft, as indicated by the increase in production of antibodies against bovine and porcine cartilage. Upon explant, all meniscal cartilage samples in this group demonstrated histological evidence of chronic rejection, including fibroplasia, encapsulation, mononuclear infiltrates, foreign body giant cells, and eosinophilic infiltrates. There was no difference between the response seen in untreated tissues and that seen in tissues treated with UV irradiation or ozone oxidation. In group 2, the menisci explanted after 1 month displayed extensive infiltration of eosinophils alone or eosinophils mixed with mononuclear cells. The mononuclear infiltrates consisted primarily of CD4+and CD8+T cells and of macrophages. The articular cartilage plugs demonstrated only a small area of fibrous encapsulation and leukocyte infiltration at the periphery. This study suggests that xenograft cartilage tissue does not appear to be immunoprivileged and is unsuitable for human implantation due to a chronic rejection mechanism, which is evident already within 1 month after transplantation. In addition, this study may serve as a general model for the primate immune response against xenografts in the absence of hyperacute rejection.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The recent advances in avoiding hyperacute rejection by producing transgenic pigs with complement regulatory proteins call for the analysis of posttransplantation changes in anti-Gal activity in the absence of hyperacute rejection. Transplantation of cynomolgus monkeys with porcine or bovine meniscus and articular cartilage enabled the study of anti-Gal IgG response to xenografts that are not subjected to hyperacute rejection. The cartilage implants were kept in suprapatellar pouches of the recipients for 1 or 2 months and anti-Gal activity was measured in the serum at various time intervals after transplantation. Within 2 weeks after transplantation, titer of anti-Gal IgG, in all transplanted monkeys, increased by 20- to 100-fold, as measured in ELISA with synthetic α-galactosyl epitopes linked to bovine serum albumin or with mouse laminin. Furthermore, binding of serum anti-Gal to porcine endothelial cells increased by 10-fold or more after transplantation. Complement-mediated cytotoxicity also increased by two- to eightfold after transplantation. The elevated activity of anti-Gal was maintained for the 2-month period during which the grafts were kept in the monkeys, and returned to the pretransplantation level 6 months after graft removal. All these data suggest that the primate immune system responds vigorously to α-galactosyl epitopes on xenografts by activating many B lymphocytes that produce increased amounts of anti-Gal IgG, which may also be of high affinity. These antibodies are likely to bind to the xenograft cells, even if these cells express low numbers of α-galactosyl epitopes. Such antibody binding may play an important role in chronic rejection of xenografts.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The present study was undertaken to investigate whether retransplantation with a second xenograft, from the same species as the primary graft, is possible to achieve using only moderate immunosuppression. Heterotopic mouse-to-rat cardiac transplantations were performed, and the recipients were treated with 15-deoxyspergualin (DSG) and cyclosporine (CsA) at high doses for days -1 to 4 and at moderate doses for days 5 to 28. From day 29 and onward, the immunosuppressive protocol consisted of daily oral administration of CsA 10 mg/kg as monotherapy. Animals that had beating grafts when DSG treatment was stopped were retransplanted 56-154 days after the primary transplantation, either with a vascularized graft (heart) or with nonvascularized graft (pancreatic islets), under continued therapy with CsA. Six of 10 secondary cardiac xenografts functioned for more than 50 days and were harvested beating after 60-100 days. In contrast, nonimmunosuppressed or DSG-treated rats are known to reject a second cardiac mouse graft hyperacutely. The unresponsiveness was confined to cardiac tissue, as the pancreatic islets, transplanted under the kidney capsule, were totally rejected after 14 days.Long-term functioning cardiac xenografts, primary and secondary, had a well-preserved morphology, and infiltrating mononuclear cells were found just in the periphery of the grafts. A majority of these cells were macrophages expressing the ED1, but not the ED2, antigen. No deposition of IgG or complement was seen in any of the graft vessels, whereas a slight deposition of IgM was observed in some vessels of both primary and secondary grafts.In conclusion, we have demonstrated that unresponsiveness can be induced by effective immunosuppression of the recipient at the time of the initial transplantation, so that retransplantation with a second xenograft can be performed successfully under single-drug immunosuppressive therapy with CsA.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Previously, isotonic solution (IS) enriched with β-hydroxybutyrate, a nonlactate-generating substrate, was shown to be efficacious in maintaining tissues' ATP and metabolic activity under cold storage. The objective of this study was to verify these findings in terms of tissue viability in vivo.Methods.Using a rabbit cornea transplantation model, efficacy of IS was studied and compared with McCarey-Kaufman medium, with or without β-hydroxybutyrate, and other known media (Optisol and Likorol), with different properties and without β-hydroxybutyrate. After storage at 4°C for 6, 7, and 11 days, the corneas were grafted, and postoperative changes in corneal thickness, and endothelial cell density and morphology were monitored with a pachymeter and specular microscope.Results.The experiments revealed that before grafting, IS effectively controlled tissue swelling for 7 days or longer, comparable to Optisol. When grafted, the IS-stored corneas deturgesced at high rates, with a short half-time (t1/2) for the de-swelling process, and the grafts remained thin and clear with an intact endothelium. This reflects excellent tissue viability. In the controls, the deturgescence process was extremely sluggish, with significantly lower rates and longert1/2(P=>0.01-0.05). Immediate swelling for 3-5 days after grafting was also observed with Optisol. These grafts had significant endothelium cell loss of 24-30% after 12 weeks (P=>0.01-0.02).Conclusions.IS is more efficacious than currently used media for sustaining the viability of donor corneas under cold storage. These findings may serve as a useful basis for future tests of IS in other organ storage systems.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.The salutary immunosuppressive effects of cyclosporine in extending cardiac allograft survival may be curtailed by its nephrotoxic effects. We reviewed our first 9 years of experience with cyclosporine after cardiac transplantation, to evaluate the incidence and progression of cyclosporine-associated end-stage renal failure necessitating chronic hemodialysis.Methods.Retrospective computer-based file review and personal interview when possible.Results.The population at risk was comprised of all adult cardiac recipients surviving at least 3 years (n=293). Of these, 19 (6.5%) developed end-stage renal failure requiring chronic hemodialysis. There were 17 men and 2 women (mean age of 45±11 years). The mean creatinine clearance for the study group decreased by 38% (P<0.001 vs. before transplant) by 6 months after transplantation and by 48% by 3 years postoperatively (P<0.001 vs. before transplant). The mean serum creatinine rose by 80% (P<0.001 vs. before transplant) by 6 months after transplantation and by 125% by 3 years postoperatively (P<0.001 vs. before transplant). Time elapsed from transplantation to hemodialysis ranged from 3.7 to 9.5 years (mean 6.4±2). Actuarial 1- year survival after onset of hemodialysis was 75%.Conclusions.Although cyclosporine remains the central immunosuppressive agent for cardiac allograft recipients, its use leads to a greater than one-third decrease in creatinine clearance by 6 months after transplantation and progression to end-stage renal failure, requiring hemodialysis in 6.5% of cardiac transplant recipients. Moreover, these patients are at increased risk of death compared with other cardiac allograft recipients. This data warrants the search of alternative or adjunctive agents that would allow decreased dosing or reduced nephrotoxicity of cyclosporine, while maintaining equivalent survival.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

In 1995, changes to the United Network for Organ Sharing renal allocation system eliminated points for certain HLA matches, increased points for waiting time and for pediatric patients, and extended the mandatory share rule to include the zero-antigen mismatch. We analyzed data, from the period December 1993 to August 1996, on 393 donors, 348 kidney-only cadaveric transplants, and 615 patients ranked first or second on the allocation lists generated for each donor, to assess the effect of the changes in the point system. There was an appreciable (46%) but not significant increase in the frequency of transplants occurring under the mandatory share rule, with a greater relative increase seen in African-Americans than in Caucasians. Recipients of transplantsnotfalling under the mandatory share rule had an increased average waiting time but no increase in sensitization or HLA mismatch, whereas patients ranked at the top of the allocation list had higher levels of sensitization but no increase in waiting time. There was an appreciable increase in the percentage of transplants occurring in African-Americans. Of the various changes we observed, only those involving the mandatory share rule could be attributed to changes in the allocation system, whereas others paralleled changes in the composition of our local waiting list.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID