他克莫司与新型免疫抑制剂FK778或FK779联合应用预防大鼠心脏移植排斥反应

目的 评价他克莫司（FK506）与FK778或FK779联合应用预防大鼠心脏移植排斥反应的效果。方法 大鼠异位心脏移植后单独应用FK506、FK778和FK779进行免疫抑制治疗，并设联合用药组。结果 单独用药组与不用药对照组相比，移植心脏存活时间明显延长，FK779组尤其显著；联合用药组移植心脏存活时间不但比对照组明显延长，而且明显长于各药同剂量单用组，FK506与FK779合用组尤其显著。结论 FK506、FK778和FK779均有很强的免疫抑制效应，FK506与FK778或FK779联合应用具有较强的协同效应。     

Synergistic effects of malononitrilamides (FK778, FK779) with tacrolimus (FK506) in prevention of acute heart and kidney allograft rejection and reversal of ongoing heart allograft rejection in the rat

BACKGROUND: The effects of tacrolimus (FK506) and malononitrilamides (MNA) (FK778 and FK779) monotherapy and combination therapy were examined in prevention of acute heart and kidney allograft rejection and reversal of ongoing acute heart allograft rejection in the rat. METHODS: Brown Norway (RT1n)-to-Lewis (RT11) and ACI (RT1a)-to-Lewis (RT11) combinations were used, respectively, for heart and kidney transplantation models. Immunosuppressants were administered orally from day 1 to day 14 for preventing acute rejection and from day 4 to day 34 after transplantation for the reversal of ongoing acute rejection. RESULTS: In the prevention of acute heart rejection model, recipient rats treated with monotherapy of tacrolimus or MNA (FK778, FK779) showed a dose-related prolongation of mean survival time (MST) compared with naive control rats (P<0.01). The mean survival time in combination therapy of tacrolimus (FK506) and FK778 indicated that an additive to synergistic interaction was produced when compared with the respective monotherapies (combination index [CI]=0.631-1.022). These results were reproducible with tacrolimus and FK779 combination therapy (CI=0.572-0.846). Furthermore, similar results were also found in the prevention of acute kidney allograft rejection in the rat (CI=0.137-0.516). In the reversal of ongoing acute heart allograft rejection, combination therapy of tacrolimus and FK778 demonstrated a strong synergistic interaction (CI=0.166-0.970) compared with monotherapy of tacrolimus or FK778. CONCLUSIONS: Combination therapy of tacrolimus and MNA (FK778, FK779) produces synergistic effects in prevention of acute heart and kidney rejection and reversal of ongoing heart allograft rejection in the rat.     

Effect of Baohuoside-1 aglycone and tacrolimus monotherapy and combination therapy on prevention of acute heart allograft rejection in the rat

Baohuoside-1 (B-1), a recently introduced novel immunosuppressant that was proved to be potent in inhibition of T and B cell proliferation and B-1, also prevents cardiac allograft rejection in rodents. The present study further proved that monotherapy of B-1's analogue B-1 aglycone effectively prolongs cardiac allograft survival and combination therapy of B-1 aglycone with tacrolimus (FK506) produces synergistic effect in prevention acute cardiac allograft rejection in the rat. .     

Synergistic effect of rapamycin and cyclosporine in prevention of acute kidney allograft rejection in the mouse

The effect of rapamycin (RAPA) and cyclosporine A (CsA) monotherapy and combination therapy was examined in prevention of kidney allograft rejection in the mouse. Both drugs were administered orally for up to 14 days in BALB/c (H-2(d)) to C57BL/6 (H-2(b)) mice strong combination. Six groups were treated with RAPA and/or CsA. This study shows that concomitant therapy of RAPA and CsA produces strong synergistic interaction in prolonging renal allograft survival in mice when compared with monotherapy of RAPA or CsA.     

他克莫司联合青藤碱抑制大鼠心脏移植急性排斥反应

目的 探讨青藤碱（SIN）对大鼠心脏移植急性排斥反应抑制作用的机制，并评价青藤碱与他克莫司（FK506）联合作用的效果。方法 以PVG大鼠为供者，DA大鼠为受者，建立同种异体心脏移植模型。将受者随机分为4组，每组20只。对照组：采用生理盐水3ml·kg^-1·d^-1灌胃；SIN组：腹腔注射SIN 30mg·kg^-1·d^-1；FK506组：采用FK506 0．25mg·kg^-1·d^-1灌胃；联合组：腹腔注射SIN 30mg·kg^-1·d^-1并联合应用FK506 0．25mg·kg^-1·d^-1灌胃。各组均在术后24h内用药，用药时间共7d。观察各组移植心存活时间，术后第7d取部分受者的移植心做病理检查，检测外周血中肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）、T细胞亚群、一氧化氮合酶（iNOS）等的浓度。结果 对照组移植心平均存活时间为（6．0±1．054）d，FK506组为（10．2±2．2）d，SIN组为（9．5±1．84）d，联合组为（16．2±2．1）d，联合组与其他3组比较，差异有统计学意义（P〈0．05）。SIN组、FK506组及联合组与对照组比较，外周血中TNF-α、IFN-γ、iNOS的表达明显减少（P〈0．05），CD4^＋T细胞亚群增殖率也明显下降（P〈0．05）。其中联合组的效果更优于SIN组和FK506组（P〈0．05）。结论 SIN能明显地抑制大鼠心脏移植急性排斥反应的发生，与FK506联合应用有协同作用。     

The interaction between FK778 and tacrolimus in the prevention of rat cardiac allograft rejection is dose dependent

OBJECTIVE: The synthetic malononitrilamide FK778 inhibits T- and B-cell responsiveness, phagocyte effector function, exerts inhibitory activity against cytomegalovirus, and is thus one of the most promising new immunosuppressive drugs. The aim of this study was to evaluate the combination of FK778 and tacrolimus in a high-responder rat cardiac transplantation model. METHODS: The Brown Norway-Lewis rat strain combination was used to investigate graft survival after 10 days of posttransplant oral therapy with FK778 (5 or 20 mg/kg), tacrolimus (2 or 8 mg/kg), or combination regimens at varying doses (5+2 mg/kg, 10+1 mg/kg, or 20+8 mg/kg). Grafts were harvested after cessation of cardiac contractions. Combination indices (CI) were calculated for drug combinations. RESULTS: In untreated recipients, allograft survival was 6.2+/-0.4 days. FK778 at 20 mg/kg and tacrolimus at 2 or 8 mg/kg significantly prolonged graft survival to a mean survival time (MST) of 17.0+/-2.8, 18.5+/-2.7, and 25.0+/-2.5 days, respectively. The two low-dose drug combinations achieved a graft survival of 23.2+/-2.9 and 25.2+/-3.1 days, which was significantly longer compared with FK778 at 5 mg/kg, FK778 at 20 mg/kg, and tacrolimus at 2 mg/kg (P 相似文献   

Synergistic interaction of 3 M KCl-extracted donor antigens (e-HAg) with cyclosporine or cyclosporine/sirolimus for prolongation of rat heart allograft survival

Extracted donor histocompatibility antigens (e-HAg) may potentiate the effects of drugs to protect organ allografts from rejection. We examined the capacity of e-HAg when combined with cyclosporine (CsA) alone, sirolimus (rapamycin, RAPA) alone, or CsA/RAPA combinations to prolong heart allograft survival in rats. Wistar-Furth (WF: RT1^u) rats that received CsA (10 mg/kg/day) by oral gavage for 3 (days 0, 1 and 2) or 7 (days 0, 1, 2, 3, 4, 5 and 6) consecutive days displayed modest prolongation of Brown Norway (BN; RT1ⁿ) heart allograft survival from a mean survival time of 7.2 ± 0.8 days in untreated controls to 12.2 ± 1.1 days and 18.6 ± 2.7 days, respectively (p < 0.01). Although administration on the day of transplantation (day 0) of a single intravenous (i.v.) dose of BN e-HAg (5 mg/kg) failed to affect allograft survival, both three (days 0, 1 and 2) and five (days 0, 1, 2, 3 and 4) injections significantly potentiated the effect of a 3-day course of oral CsA (18.6 ± 1.3 days (p < 0.01) and 20.0 ± 1.4 days (p < 0.01), respectively) and of a 7-day course of oral CsA (25.3 ± 4.4 days (p < 0.05) and 33.5 ± 9.3 days (p < 0.01), respectively). Median-effect analysis confirmed a synergistic interaction between CsA (0.5 mg/kg × 7 days, i.v.) and e-HAg with combination index (CI) values less than 0.7 (CI = 1 shows additive interactions, CI < 1 synergistic, and CI> 1 antagonistic, interactions). In contrast, e-HAg failed to affect the immunosuppressive effect of RAPA. However, e-HAg (5.0 mg/kg × 3 days) significantly potentiated the effects of a 7-day or 14-day course of RAPA (0.01 mg/kg)/CsA (0.5 mg/kg) combination therapy, namely from 26.0 ± 4.8 days with a 7-day treatment of CsA/RAPA alone to 32.6 ± 3.6 days (p < 0.01) and from 28.2 ± 2.7 days with a 14-day course of CsA/RAPA alone to 42.0 ± 4.9 days (p < 0.05), respectively (CI = 0.2–0.5). Thus, e-HAg potentiates the immunosuppressive effects of CsA alone and of the CsA/RAPA combination, but not of sirolimus alone.     

他克莫司胶囊和缓释胶囊预防肝移植急性排斥反应的效果和安全性

Objective To evaluate the efficacy and safety of tacrolimus exposure in stable liver transplant recipients converted from FK506 twice a day to Advagraf (tacrolimus extended-release capsules) once daily. Methods This was an open-label, random, control and multi-center study.Eligible patients were 19 to 70 years of age, 6 months post-transplant with stable renal and hepatic function and receiving stable doses of tacrolimus twice a day for 2 weeks prior to enrollment. There were 86 patients in the experimental group and the control group, separately. The average age of experimental group and control group was 46 ± 10 and 49 ± 9, respectively. Patients in experimental group received Advagraf, once daily, and the dose was adjusted according to the drug concentration,and the drug concentration was between 2 to 10 μg/L. The control group given tacrolimus, twice daily, and the drug concentration was between 2 to 10 μg/L. Results The incidence of acute rejection reaction was 1.20 % and 1.18 % respectively in experimental group and control group, and the 95 %confidence interval was -3.25% ～3.31 % and -3.26% ～ 3.34 %, individually. There was 1 case of acute rejection reaction in experimental group and control group, respectively. The patient and organ survival rate was 100%. Sixteen adverse events occurred in 15 patients (17.65 %) of the experimental group, and 10 adverse events occurred in 10 patients (11.63 %) of control group. Severe adverse events relating to the test drug in experimental group occurred in 4 patients (4. 71 %). and 2 patients (2. 33) in control group.Conclision Clinical trials indicated that Advagraf has efficacy and safety profiles similar to those of tacrolimus. The drug is safe and may improve patient compliance.     

他克莫司胶囊和缓释胶囊预防肝移植急性排斥反应的效果和安全性

Objective To evaluate the efficacy and safety of tacrolimus exposure in stable liver transplant recipients converted from FK506 twice a day to Advagraf (tacrolimus extended-release capsules) once daily. Methods This was an open-label, random, control and multi-center study.Eligible patients were 19 to 70 years of age, 6 months post-transplant with stable renal and hepatic function and receiving stable doses of tacrolimus twice a day for 2 weeks prior to enrollment. There were 86 patients in the experimental group and the control group, separately. The average age of experimental group and control group was 46 ± 10 and 49 ± 9, respectively. Patients in experimental group received Advagraf, once daily, and the dose was adjusted according to the drug concentration,and the drug concentration was between 2 to 10 μg/L. The control group given tacrolimus, twice daily, and the drug concentration was between 2 to 10 μg/L. Results The incidence of acute rejection reaction was 1.20 % and 1.18 % respectively in experimental group and control group, and the 95 %confidence interval was -3.25% ～3.31 % and -3.26% ～ 3.34 %, individually. There was 1 case of acute rejection reaction in experimental group and control group, respectively. The patient and organ survival rate was 100%. Sixteen adverse events occurred in 15 patients (17.65 %) of the experimental group, and 10 adverse events occurred in 10 patients (11.63 %) of control group. Severe adverse events relating to the test drug in experimental group occurred in 4 patients (4. 71 %). and 2 patients (2. 33) in control group.Conclision Clinical trials indicated that Advagraf has efficacy and safety profiles similar to those of tacrolimus. The drug is safe and may improve patient compliance.     

他克莫司胶囊和缓释胶囊预防肝移植急性排斥反应的效果和安全性

Objective To evaluate the efficacy and safety of tacrolimus exposure in stable liver transplant recipients converted from FK506 twice a day to Advagraf (tacrolimus extended-release capsules) once daily. Methods This was an open-label, random, control and multi-center study.Eligible patients were 19 to 70 years of age, 6 months post-transplant with stable renal and hepatic function and receiving stable doses of tacrolimus twice a day for 2 weeks prior to enrollment. There were 86 patients in the experimental group and the control group, separately. The average age of experimental group and control group was 46 ± 10 and 49 ± 9, respectively. Patients in experimental group received Advagraf, once daily, and the dose was adjusted according to the drug concentration,and the drug concentration was between 2 to 10 μg/L. The control group given tacrolimus, twice daily, and the drug concentration was between 2 to 10 μg/L. Results The incidence of acute rejection reaction was 1.20 % and 1.18 % respectively in experimental group and control group, and the 95 %confidence interval was -3.25% ～3.31 % and -3.26% ～ 3.34 %, individually. There was 1 case of acute rejection reaction in experimental group and control group, respectively. The patient and organ survival rate was 100%. Sixteen adverse events occurred in 15 patients (17.65 %) of the experimental group, and 10 adverse events occurred in 10 patients (11.63 %) of control group. Severe adverse events relating to the test drug in experimental group occurred in 4 patients (4. 71 %). and 2 patients (2. 33) in control group.Conclision Clinical trials indicated that Advagraf has efficacy and safety profiles similar to those of tacrolimus. The drug is safe and may improve patient compliance.     

他克莫司胶囊和缓释胶囊预防肝移植急性排斥反应的效果和安全性

目的 研究稳定期的肝移植受者分别服用他克莫司缓释胶囊和他克莫司胶囊在预防急性排斥反应的效果和安全性方面的差异.方法 采用多中心、随机、开放、对照的研究方法.试验组和对照组入组的稳定期肝移植受者各86例.试验组受试者的年龄为(46±10)岁;对照组受试者的年龄为(49±9)岁.试验组口服他克莫司缓释胶囊,每天1次,根据血药浓度谷值调整药量,维持血药浓度谷值为2～10 μg/L;对照组口服他克莫司胶囊,每天2次,维持血药浓度谷值为2～10 μg/L.结果 试验组和对照组分别有1.20%和1.18%的受试者发生急性排斥反应,两组的95%可信区间分别为-3.25%～3.31%和-3.26%～3.34%,可信区间上限均低于10%的非劣效标准.试验组和对照组急性排斥反应的发生率分别为1.20%和1.18%,两组患者发生急性排斥反应的次数均为1次,患者及移植物的存活率均为100%,以上指标两组间的差异均无统计学意义(P＞0.05).试验组有15例(占17.65%)共发生16次与试验药物相关的不良反应,对照组有10例(11.63%)共发生10次与试验药物相关的不良反应;试验药物有关严重不良反应中,试验组有4例(占4.71%)共发生4次,对照组有2例(占2.33%)共发生2次.两组不良反应发生率的差异均无统计学意义.结论 稳定期肝移植受者服用他克莫司缓释胶囊和他克莫司胶囊在预防急性排斥反应的疗效和安全性方面无明显差异.

Abstract：

Objective To evaluate the efficacy and safety of tacrolimus exposure in stable liver transplant recipients converted from FK506 twice a day to Advagraf (tacrolimus extended-release capsules) once daily. Methods This was an open-label, random, control and multi-center study.Eligible patients were 19 to 70 years of age, 6 months post-transplant with stable renal and hepatic function and receiving stable doses of tacrolimus twice a day for 2 weeks prior to enrollment. There were 86 patients in the experimental group and the control group, separately. The average age of experimental group and control group was 46 ± 10 and 49 ± 9, respectively. Patients in experimental group received Advagraf, once daily, and the dose was adjusted according to the drug concentration,and the drug concentration was between 2 to 10 μg/L. The control group given tacrolimus, twice daily, and the drug concentration was between 2 to 10 μg/L. Results The incidence of acute rejection reaction was 1.20 % and 1.18 % respectively in experimental group and control group, and the 95 %confidence interval was -3.25% ～3.31 % and -3.26% ～ 3.34 %, individually. There was 1 case of acute rejection reaction in experimental group and control group, respectively. The patient and organ survival rate was 100%. Sixteen adverse events occurred in 15 patients (17.65 %) of the experimental group, and 10 adverse events occurred in 10 patients (11.63 %) of control group. Severe adverse events relating to the test drug in experimental group occurred in 4 patients (4. 71 %). and 2 patients (2. 33) in control group.Conclision Clinical trials indicated that Advagraf has efficacy and safety profiles similar to those of tacrolimus. The drug is safe and may improve patient compliance.     

Interleukin 2 receptor in rat heart allograft rejection

Soluble interleukin 2 receptors (S-R-IL-2) of truncated Tac chain, produced in vitro during T lymphocyte activation, may represent an in vivo marker of an alloimmune reaction. We analyzed serum S-R-IL-2 production during acute heart allograft rejection and compared soluble and membranous Tac chain (blood lymphocytes and graft invading cells) regulation during rejection. Serum S-R-IL-2 was tested in an immunoradiometric assay, with a combination of two mouse IgG1 anti-IL2-R mAbs (ART18 and OX39). Membranous Tac chain was analyzed by immunochemistry in graft tissue, and by immunofluorescence on blood and spleen leukocytes. Four experimental groups were used: untreated allogeneic, untreated syngeneic, CsA-treated (10 mg/kg/day for 15 days) allogeneic and CsA-treated syngeneic graft recipients. In the untreated allogeneic group, S-R-IL-2, tested every day until rejection (9.14 +/- 1.6 days), increased as early as day 3 after transplantation, peaked at day 6, and plateaued thereafter. The allograft was infiltrated at day 5 by Tac chain-positive cells (10% of OX1 cells and 84% of OX19 cells). A small percentage of mononucleated cells was labeled in blood, but not in spleen, by ART18 and OX39 at day 7 only. In contrast, in untreated syngeneic and CsA-treated allogeneic combinations, there was no increase of baseline S-R-IL-2 level (P less than 0.001), and graft infiltrate did not contain IL-2-R positive cells. CsA treatment prolonged heart allograft survival (41.3 +/- 2.8 days). Baseline S-R-IL-2 levels during treatment were lower than those observed in untreated animals. In the CsA-treated allogeneic group, after CsA treatment interruption, S-R-IL-2 levels significantly increased, reaching a plateau at day 37. Results suggest that S-R-IL-2 measurement can be useful for clinical diagnosis of allograft rejection.     

Prolongation of rat cardiac allograft survival by treatment with prostacyclin or aspirin during acute rejection

Hearts taken from DA (RT1a) rats were transplanted heterotopically to PVG (RT1c) rats of the same sex (day 0). On day 1 or on day 5 rats were treated with prostacyclin (PGI2), 250 ng/kg/min, by continuous infusion of alkaline solution into the inferior vena cava until the time of rejection. Controls received glycine buffer infusion alone, from day 1 or day 5. Cessation of palpable graft beat was taken as the end point of rejection. When PGI2 was infused from day 5 median graft survival time was prolonged from a control of 7.8 days to 9.3 days (P less than 0.05). When PGI2 was infused from day 1, graft survival time was prolonged from a control of 7.4 days to 8.6 days (P less than 0.05). Other groups of rats were treated from day 1 or from day 5 with aspirin (acetylsalicylic acid), 200 mg/kg/day, by 8-hourly subcutaneous injection in saline. Control groups received saline alone. When aspirin was given from day 5, graft survival time was prolonged from a control of 7.3 days to 9.5 days (P less than 0.05). When aspirin was given from day 1 graft survival time was prolonged from a control of 7.2 days to 14.9 days (P less than 0.01), and in two cases this led to very prolonged survival. Histological examination at the time of rejection showed lymphocyte and neutrophil infiltration to be much more prominent than vessel occlusion in all groups. These results imply that PGI2 and aspirin may be beneficial to graft survival in acute rejection, but this is not due to reduced occlusion of blood vessels by platelets.     

肾移植术后西罗莫司联合减量或停用环孢素A的应用体会

,患者存活率为86.7%.至4年随访终点,存活26例患者中25例移植肾功能良好.2例发生急性排斥反应,经甲泼尼龙冲击治疗后逆转.17例次发生感染,经抗感染处理后全部康复.2例术后发生移植肾功能恢复延迟,免疫抑制方案未做调整,分别在术后32 d和58 d恢复泌尿.结论 肾移植术后采用SRL联合CsA和糖皮质激素作为初始治疗,术后3个月开始减少直至停用CsA是有效、安全和可行的.     

Early experience with sirolimus in lung transplant recipients with chronic allograft rejection.

BACKGROUND: Chronic lung allograft rejection, commonly manifest as obliterative bronchiolitis (OB/BOS), hinders long-term survival after lung transplantation (LT). OB/BOS is traditionally treated with augmented immunosuppression and results in short-term stabilization in pulmonary function for most patients. However, peribronchiolar fibroproliferation and airway obstruction usually recur despite initial improvements seen with increases in immunosuppression. In this observational, uncontrolled study, the effect of sirolimus, a novel immunosuppressant with anti-proliferative activity, was assessed in LT patients with OB/BOS. METHODS: Between June 1999 to November 2000, LT recipients with newly diagnosed or progressive OB/BOS received sirolimus in combination with a calcineurin inhibitor (CI) and prednisone. Pulmonary function, laboratory data and adverse effects were monitored for the first 24 weeks of therapy. RESULTS: Sirolimus was utilized in 12 LT recipients with OB/BOS. After drug initiation, 58% of patients required a reduction in CI dose to maintain appropriate CI trough concentrations. Despite CI dose reduction, serum creatinine rose in 75% of patients. Unexpected adverse effects included anemia of chronic disease (100%), edema (50%) and malignancy (17%). For the group, the rate of change in FEV(1) and FEF(25%-75%) was unchanged with sirolimus, but individual responses varied. CONCLUSIONS: For the group, the decline in pulmonary function was not affected by the addition of sirolimus. However, among individuals with rapidly declining pulmonary mechanics, sirolimus resulted in stabilization or improvement in pulmonary function. Significant adverse effects resulted from combination sirolimus plus CI therapy. Until optimal dosing strategies and a more complete adverse effect profile are established, combination therapy should be utilized cautiously in these patients.     

International experience with conversion from cyclosporine to tacrolimus for acute and chronic lung allograft rejection

OBJECTIVE: A retrospective study involving 13 institutions was performed to assess the efficacy of conversion from cyclosporine (INN: ciclosporin) to tacrolimus. METHODS: Data from 244 patients were analyzed. Indications for conversion were recurrent-ongoing rejection (n = 110) and stage 1 to 3 bronchiolitis obliterans syndrome (n = 134). RESULTS: The incidence of acute rejection decreased significantly within 3 months after versus before the switch from cyclosporine to tacrolimus (P <.01). For patients with recurrent-ongoing rejection, the forced expiratory volume in 1 second decreased by 1.96% of predicted value per month (P =.08 vs zero slope) before and increased by 0.34% of predicted value per month (P =.32 vs zero slope) after conversion (P <.06). For patients with stage 1 to 3 bronchiolitis obliterans syndrome, a significant reduction of rejection episodes was observed (P <.01). In single transplant recipients a decrease of the forced expiratory volume in 1 second averaged 2.25% of predicted value per month (P <.01 vs zero slope) before and 0.29% of predicted value per month after conversion. Corresponding values for bilateral transplant recipients were 3.7% of predicted value per month (P <.01 vs zero slope) and 0.9% of predicted value per month (P = 0.04 vs zero slope), respectively. No significant difference in the incidence of infections within 3 months before and after conversion was observed. CONCLUSIONS: Conversion from cyclosporine to tacrolimus after lung transplantation is associated with reversal of recurrent-ongoing rejection. Conversion for bronchiolitis obliterans syndrome allows short-term stabilization of lung function in most patients.     

A modified rat model of acute limb allograft rejection

Background

The purpose of this study was to determine the feasibility of a simplified model of acute limb allograft rejection.

Methods

Wistar rats were donors (n = 18), and Sprague-Dawley (SD) rats were recipients (n = 36). They were divided into a traditional and a modified model group. In the traditional group, the hind limb of the recipient was removed; blood vessels, bone, and nerve anastomoses were performed. In the modified group, the hind limb of the recipient was maintained while the allografted limb was transplanted near inside the original hind limb with only blood vessel anastomoses performed, and the donor limb was fixed in place by suturing muscle and skin.

Results

The ischemic time of the donor limbs in the modified group was significantly less than the traditional group (67 ± 19.1 minutes vs 127 ± 15 minutes; P < .0001). In the traditional group, 12 models (66.7%) were successful and 6 failed, whereas in the modified group, 17 (94.4%) were successful and 1 failed (P = .087). Acute rejection occurred in all surviving rats; the time and characteristics of rejection were similar in the 2 groups.

Conclusions

The simplified rat hind limb allotransplantation model described herein offers a greater success rate and shorter operative time than the traditional model while providing the same rejection characteristics.