ISSN:0041-1337    

出版商:OVID    

年代:1991

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The effect of donor-specific blood transfusion (DST), in combination with pretransplant immunosuppression with deoxyspergualin (DSG), on hamster-to-Wistar rat cardiac xenograft survival was assessed. While DST given on day −6 sensitized the recipients, resulting in hyperacute xenograft rejection, the addition of 5 mg/kg/ k/day DSG from the day of transfusion to the day of grafting not only prevented hyperacute rejection but resulted in prolongation of graft survival from 3.4±0.5 days in untreated controls to 7.0±0.7 days (P< 0.01). In contrast, DSG alone as pretransplant immunosuppression had no beneficial effect and rejection occurred in 4.0±0.7 days. This effect appears to be at least donor species-specific, in the sense that ACI cardiac allograft survival was not prolonged when transplanted into xenotransfused and DSG-treated Wistar recipients. DST alone resulted in marked increase in antibody tiers, showing the value of 1:512 or more on transplantation day. On the other hand, combined treatment suppressed the titers to 1:1–1:4 on that day. An adoptive cell transfer system was used to analyze the mechanisms underlying this effect. When sublethally irradiated secondary hosts were transferred with 5×107lymph node cells (LNCs) harvested on day 0 from xenotransfused and DSG-treated rats, the test heart xenograft survived longer than the irradiated and nontransferred controls, suggesting the presence of suppressor cells., Further in vitro studies demonstrate that LNCs from DST+DSG-treated rats response less in a mixed lymphocyte reaction to hamster LNCs (41% on day 0 [P< 0.01]), compared with the controls. In coculture experiments, the LNCs from treated recipients suppressed the response of unmodified Wistar LNCs to hamster LNCs by 76% on day 0 compared with the positive controls (P< 0.01). On the other hand, the transfer of serum taken from treated rats on day 0 did not lead to prolongation of test heart xenografts in syngeneic naive hosts. These findings suggest that the mechanisms underlying the hypo-responsiveness induced by pretreatment with DST and DSG include the induction of suppressor cells, although a degree of clonal deletion can not be ruled out. The generation of serum suppressor factors seems to have no role in this phenomenon.

ISSN:0041-1337    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The purpose of the present study was to achieve prevention of immune rejection in rat islet allografts by FK506. WKA/Qdj (RT1u) islets were transplanted either into the liver via the portal vein (p.v.) or beneath the kidney capsule (k.c.) of streptozotocin (60 mg/kg) induced diabetic Lewis (RT11) rats. Fresh or cultured (24°C, 1 week) islets were used as donors. A mini-osmotic pump (0.2 ml, Alzet 2001) containing 5 mg FK was implanted s.c. at the time of transplantation for continuous delivery of FK506 for 7 days after transplantation. The mean survival time (MST) of the fresh p.v. grafts with a pump was >61.4±37.2 days (mean ± SD, n=17) (control 5.5±0.6, n=4). Ten out of 17 were normoglycemic for more than 90 days after transplantation. When low-temperature cultured islets were used and FK506 was delivered for 7 days, all the rats were normoglycemic for more than 90 days after transplantation. The MST of the fresh or cultured k.c. grafts with a pump was 22.0±14.2 or 24.7±5.0 days, respectively. Long-term administration of FK506 by repeated implantations (5 times; days 0, 7, 14, 21, and 28) of pumps containing 5 mg FK506 produced marked prolongation of the fresh or cultured k.c. graft survival with an MST of >58.7±22.1 or >56.9±18.0 days, respectively. These findings clearly demonstrate that the prevention of immune rejection in the islet allografts transplanted into the liver was achieved by short-term post-transplant administration of FK506 and low-temperature culture of donor islets, and also show that long-term continuous administration of FK506 was needed for the prolongation of the graft survival when the renal

ISSN:0041-1337    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Previously, we have shown that a perioperative injection of donor mononuclear cells in combination with cyclosporine treatment on day 2 after transplantation prolongs heart allograft survival in rats. In this study we determined whether the efficacy of this treatment was influenced by the same factors that have been shown to affect the efficacy of preoperative administration of donor cells. The effect of the following factors were investigated: dosage and repetition of the donor cell injection, viability of the donor cells, immunosuppressive drugs other than cyclosporine, and the rat strain combination. We found that there was an optimal dosage of donor cells; dosages of 4×l07or l×108cells gave the best heart graft survival. Repetition of the donor cell injection was not useful. Reducing viability of the cells by irradiation did not abrogate the prolonged graft survival, whereas killing of the cells did. Methylprednisolone, azathioprine, or cyclophosphamide in combination with the perioperative donor cell injection did not prolong heart graft survival in comparison with treatment with the drug only. The efficacy of this treatment was also influenced by the rat strain combination. In some combinations, this treatment prolonged graft survival, whereas in others an effect was absent or undetectable. Importantly, this treatment never adversely affected graft survival.We conclude that the efficacy of this treatment is influenced by similar factors as found for preoperative treatment with donor cells. A major advantage of this treatment over preoperative blood transfusions is that it avoids sensitization.

ISSN:0041-1337    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We studied the efficacy of defibrotide, a prostacyclin-stimulating agent, in preventing ischemia reperfusion injury in Wistar rat heart by using three experimental models: (1) hearts from donors were perfused with the drug (32 mg/kg/hr) during 15, 30, 45, and 60 min of cold ischemia following 5, 10, and 15 min of warm ischemia; (2) hearts from donors treated with the drug were cold-stored for 12 or 24 hr; and (3) procured hearts perfused with the drug were isografted, after 30 or 60 min of warm ischemia, in recipient rats treated daily with defibrotide. Hearts perfused with saline and/or vehicle of the drug were used as controls. At the end of established ischemia times, and after 30 min, and 2, 4, 7 and 14 days from transplantation, hearts were rapidly cooled in liquid nitrogen. ATP, ADP, AMP, cAMP contents, and NAD+/NADH ratios were evaluated in prepared tissue extracts. Cardiac ATP and ADP levels and NAD+/NADH ratios were significantly higher in defi-brotide-treated organs than in controls. Isografted defibrotide-treated hearts were also significantly preserved, with respect to controls, from the loss of ATP levels until rejection occurred. Our results demonstrate the protective activity of the drug against the myocardial metabolic damage due to ischemia-reperfusion.

ISSN:0041-1337    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The effect of pretreatment with cyclosporine on liver preservation was studied using a rat liver transplant model. In a preliminary 1-week survival study, 59 liver transplants were performed. In group A, neither donors nor recipients were treated. In group B, the recipients were pretreated by a 3-day course of CsA (10 nag/kg/ day, p.o.), but the donors were untreated. In group C, the donor rats were pretreated for 3 days with the same doses of CsA as in group B, but the recipients were not treated. The donor livers in each group were stored for 12 hr at 4°C with Eurocollins solution and transplanted to the recipients. The CsA pretreatment to recipients (group B) significantly improved 1-week survival (57.1%, 8/14,P<0.01 versus control group A; 0%, 0/14 or group C; 14.3%, 2/14).To study lipid peroxidation and morphology, 72 rat livers were studied in 9 groups. In summary, CsA pretreatment to recipients resulted in suppression of the increase in MDA levels and amelioration of endothelial injury after transplantation. On the other hand, donor pretreatment exerted dual effects on the grafts; it ameliorated endothelial injury after reperfusion, but its heptotoxic action exacerbated hepatocellular damage during hypothermic storage.Our study suggests that CsA pretreatment, particularly to recipients, is beneficial in liver preservation for hepatic transplantation. The mechanisms are discussed with regard to ischemia/reperfusion injury to hepatic endothelium.

ISSN:0041-1337    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Limited availability of donor organs is a major factor restricting the clinical application of lung transplantation. Improvements in preservation techniques are essential for prolonging storage time and improving lung function following transplantation. The present investigation used primary cultures of adult rat alveolar type II cells as a model for evaluating lung-preservation solutions. Type II cells were plated onto tissue-culture plastic at a density 5×105cells/cm2and maintained in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum (D10) for 40 hr. Cells were then exposed to Euro-Collins solution or a low-potassium-dextran solution (LPD). At designated time points, measurements of lactate-dehydrogenase (LDH) release, protein content, and incorporation of3H-thymidine into cellular DNA were made. During 12 hr of “storage” at 37°C, cells maintained in LPD released less LDH (14.3± 1.2% of cellular total, mean ±SEM, n=5) than their

ISSN:0041-1337    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We studied the effect of a vasodilator (prostaglandin E1) as well as flush (F) and storage (S) temperatures (4°C or 10°C) on lung preservation in an isolated rabbit lung perfusion model. Low-potassium dextran (LPD) or Euro-Collins (E-C) solution was used as flush solution. Six groups of six animals were studied: group 1 (LPD, 4°C F-S), group 2 (LPD with PGE, 4°C F-S), group 3 (E-C with PGE, 4°C F-S), group 4 (LPD, 10°C F-S), group 5 (LPD with PGE1, 10°C F-S), group 6 (E-C with PGE1, 10°C F-S). After 18-hr preservation, left lungs alone were ventilated, and reperfused with fresh venous blood. PaO2, PaCO2, pulmonary artery pressure (PAP), tracheal pressure (P1) during reperfusion, and wet/dry weight (W/D) ratios were measured. PaO2after LPD with or without PGE1was significantly higher than after E-C with PGEi at 4°C (95.8±11.5 mmHg in group 1 or 102.7±8.6 in group 2 vs. 41.8±10.5 in group 3,P>0.01) and at 10°C (119.3±2.3 in group 4 or 131.1± 6.2 in group 5 vs. 54.6±5.2 in group 6,P>0.01). PaCO2, PAP, P1, and W/D ratios in the LPD groups were lower than in the E-C groups. LPD/PGE1and LPD alone produced similar pulmonary preservation. PaO2of lungs flushed with LPD and preserved at 10°C was higher than that of lungs stored at 4°C. We conclude that LPD solution is superior to E-C solution in this ex vivo rabbit lung preservation model, even when PGE1is used. A moderate dose of PGE1did not improve the performance of LPD as a flush solution. Pulmonary preservation with LPD at 10°C is superior to preservation at 4°C.

ISSN:0041-1337    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Urinary levels of trypsinogen and active trypsin were measured in 34 urine samples from 14 patients an average of 23 months following whole organ pancreas transplantation and duodenocystostomy. Timed urine specimens obtained 30 min and 90 min following a time zero void were collected from 5 patients in an effort to define the kinetics of trypsinogen secretion and activation. Total urinary protein and urinary pH were correlated with urinary levels of trypsin and trypsinogen. Twenty-one specimens from 8 normal volunteers and a single specimen from a pancreas transplant patient with a duodenoenterostomy served as controls.Activated trypsin was present in 33 of 34 specimens from 13 of the 14 transplant patients. The average total trypsin activity in all samples was 84.4 μg/ml urine (±SE 9.6). Trypsinogen was present in 13 of 34 samples, from 7 of 14 patients. The average trypsinogen concentration of all 34 samples was 9.6±6.2 μg/ml. No trypsin or trypsinogen activity was identified in any control sample. In the 5 patients undergoing timed urine collections total trypsin increased an average of 1.3-fold at 30 min and 1.1-fold at 90 min relative to time zero. Urinary trypsinogen increased an average of 7.1-fold at 30 min and 3.1-fold at 90 min following the initial void. Urinary pH and total urinary protein failed to show a significant correlation with urinary levels of total trypsin or trypsinogen.These data suggest that trypsinogen is rapidly converted to active trypsin following secretion into the bladder, resulting in the high urinary trypsin levels that were detected in the majority of patients.

ISSN:0041-1337    

出版商:OVID    

年代:1991

数据来源: OVID