Histologic assessment of bronchial anastomotic healing in canine lung transplantation

Postoperative wound healing of the bronchial anastomosis was studied in dogs with autotransplantation (20 dogs, 7 days to 6 years postoperatively) and allotransplantation (62 dogs, 5 to 174 days postoperatively) of the left lung. In the group undergoing lung allotransplantation, the relationship among three histologic parameters was studied: the grade of lung allograft rejection, the degree of changes in the epithelium, and submucous lymphocyte infiltration along the donor bronchus within approximately a 0.5 cm area distal to the anastomosis. In lung autotransplantation, mucosal continuity began to be observed 1 week postoperatively. Mucosal continuity and apparent collagen formation on any bronchial contiguous site were demonstrated in most animals studied more than 3 weeks postoperatively. Bronchial anastomotic healing tended to be slower in lung allotransplantation than in autotransplantation, although a mucosal continuity at the anastomosis was sporadically observed in immunosuppressed dogs surviving more than 3 weeks postoperatively with a lung allograft. There were significant rank correlations among the three histologic parameters, which showed that lung allograft rejection is closely connected with wound healing of the bronchial anastomosis in lung allotransplantation. Meticulous mucosal approximation is most necessary during bronchial anastomotic procedures. Establishment of an exact method for early monitoring of lung allograft rejection is absolutely necessary for lung allotransplantation.     

Histologic studies on canine lung transplantation

Histologic and functional investigation on lung allotransplantation was performed in 26 mongrel dogs divided into major two groups. In Group A left lung allotransplantation was carried out. These dogs were followed by administration of Cyclosporin A and Azathioprine. In dogs of Group B left lung allotransplantation and postoperative measurement of pulmonary artery (PA) pressure by contralateral PA occlusion test using modified Swan-Ganz catheter were performed. This group was subdivided into 4 groups; Group B-I: 6 hours preservation of donor's lung and administration of Cyclosporin A and Azathioprine. Group B-II: no preservation of donor's lung and administration of Cyclosporin A and Azathioprine. Group B-III: Group B-II + steroid and Group B-IV: Group B-I + steroid. In many dogs the prolongation of occurrence of acute rejection was observed Cyclosporin A. In Group A the fibrotic changes around the blood vessel and/or bronchus were detected occasionally. The appearance and desquamation of atypical type II cells were present in a few dogs. In Group B the characteristic features of acute rejection were observed. Histologic differences between groups of immediate transplantation (B-II & III) and groups with preserved lung for 6 hours (B-I & IV) were not demonstrated. There was no definite case of so-called "alveolar rejection". The mean-PA pressure of Group B rose up just after the transplantation in every dog. On postoperative 7th day the PA pressure after the right PA occlusion decreased, however it elevated again on 14th day except one dog, because of the diffuse mononuclear cell cuffing around blood vessel walls. We believe that this test is an useful examination for the evaluation of occurrence and intensity of rejection.     

Synergistic effect of low dose Cyclosporine A and human interleukin 10 overexpression on acute rejection in rat lung allotransplantation

Objective: Electroporation mediated transfer of plasmid DNA into peripheral muscle results in high transfection efficiency. The aim of this study was to investigate the effect of gene transfer of human IL-10 (hIL-10) into the tibialis anterior muscle (MTA) in combination with low dose Cyclosporine A (CsA) on acute rejection of lung allografts in the rat. Methods: Lung allotransplantation was performed from male BN donor to male Fisher F344 rats. Gene transfer was achieved by intramuscular injection into the MTA of the recipient followed by electroporation (4×20 ms impulses at 200 V/cm) 24 h prior to the transplantation. Group A (n=5) received CsA (2.5 mg/kg bw ip) for 5 days post-transplant and group B (n=5) 2.5 μg of PCIK hIL-10 (plasmid expression vector containing human CMV immediate early gene promoter and enhancer) and a low dose CsA (2.5 mg/kg bw i.p.). Graft function was assessed by blood gas at day 5 after exclusion of the native lung. Animals were sacrificed and blood was drawn to measure serum hIL-10 levels (ELISA) and tissue was sampled for histological grading of rejection. Results: Local expression of hIL-10 was confirmed at the mRNA level by in situ hybridization. All group A control animals showed severe signs of rejection. At day 5 all grafts in group B showed good gas exchange mean PaO2 233±123 mmHg, vs 44±8 mmHg in group A. Histological examination revealed moderate to severe rejection in all animals in group A (IIIB, ISHLT) in contrast to low moderate rejection in group B (II–IIIA). hIL-10 serum levels on day 5 were 14±7 pg/ml in group B vs. 0 in group A. Conclusions: Electroporation mediated hIL-10 overexpression in a peripheral muscle of the recipient in combination with low dose CsA reduces acute rejection in this model of rat lung allotransplantation.     

兔半侧颜面移植模型

目的 为异体颜面移植（换脸）的研究建立一种动物模型.方法 以青紫蓝兔及新西兰大白兔为实验动物,应用颈外动脉携带其分支颌外动脉和耳大动脉为蒂,获得半侧颜面游离复合组织瓣,进行同种异体移植,其中青紫蓝兔为受体、新西兰大白兔为供体.术后观测复合组织瓣的存活情况,检验实验动物模型的可行性.结果 通过美蓝显示应用本程序获得的游离复合组织瓣模型,依靠颈外动脉供血,可以保证其存活.结论 本实验程序可以作为研究异体颜面移植的一种良好模型.     

Immunosuppression with aerosolized cyclosporine for prevention of lung rejection in a rat model

The efficacy of local delivery of aerosol cyclosporine (CsA) for prevention of lung rejection was compared with the intramuscular route (IM) in a fully allogeneic rat model (BN/LEW) of lung transplantation (LTx). Control rats (group 1, n = 6) received no CsA after LTx. Rats in group 2 (n = 10) received 4 doses of CsA in olive oil (25 mg/kg) intramuscularly starting on postoperative day (POD) 0. Group 3 (n = 9) was treated with aerosolized CsA for 3 h/day for 7 days starting on POD 0. All animals were sacrificed on POD 6. Transplanted lungs were graded histologically in a blind manner on a 0-4 scale. Control animals all showed grade 4 rejection. i.m. CsA therapy reduced lung rejection with a rejection grade of 1.8 +/- 0.35 (mean +/- SD) but was associated with a 50% incidence of pneumonia. Aerosol CsA provided better control of rejection with a rejection grade of 1.2 +/- 0.4 (group 3 vs. group 2: P less than 0.05 Wilcoxon) and none of these animals had penumonia. Trough blood levels of CsA were significantly lower in the group treated with aerosolized CsA when compared with the IM group (P less than 0.05). Therefore we conclude that: (1) aerosol CsA is effective in preventing lung allograft rejection following lung transplantation in rats, and (2) local delivery of aerosol CsA is superior to the i.m. route because better control of rejection is achieved with a lower systemic delivery of CsA.     

Improved immunosuppression with aerosolized cyclosporine in experimental pulmonary transplantation.

Rejection remains a major obstacle to long-term success of pulmonary transplantation. Direct delivery of cyclosporine to lung allografts may produce better control of rejection by generating high intragraft concentrations of drug with decreased systemic delivery and toxicity. The efficacy of inhaled cyclosporine in preventing allograft rejection was compared with systemic delivery by intramuscular injections in a rat model of lung transplantation (Brown-Norway to Lewis). Group 1 animals were given no immunosuppression. Group 2 received a single i.m. injection of 25 mg/kg CsA on the day of operation while group 3 received daily doses on postoperative days 0-3. Groups 4-7 received aerosolized CsA daily for seven days. The aerosol generator produced an airborne concentration of CsA of 180 mg/m3 with a mean particle size of 0.7 mu and estimated pulmonary depositions of CsA of 0.98-3.6 mg/kg/day. Animals were killed on POD 7, and the transplanted lungs graded histologically in a blinded fashion. All control animals showed destructive grade 4 changes by POD 7. Animals receiving high-dose aerosolized CsA (groups 6 and 7) showed minimal changes with a mean rejection grade of 1.3. A single i.m. dose of CsA (group 2) failed to prevent rejection; the mean grade was 2.2. Animals given four i.m. doses of CsA had a mean grade of 1.8. Aerosolized CsA provided significantly better control of rejection than did systemic CsA (groups 6 and 7 vs. groups 2 and 3; P less than 0.0002 and less than 0.0054, respectively). Local delivery of CsA by aerosol inhalation is effective in limiting acute rejection of the rat lung allograft.     

Fas ligand gene transfer combined with low dose cyclosporine A reduces acute lung allograft rejection

Abstract The interaction between Fas and its ligand (FasL) induces apoptosis in the Fas‐expressing cell. We hypothesized that liposome‐mediated FasL gene transduction to the lung allograft, in addition to low‐dose immunosuppression, might reduce acute rejection. Orthotopic left lung allotransplantation was performed in male rats (Brown Norway to Fischer F344). FasL gene transfer was performed by use of the plasmid pBCMGSNeo carrying the gene coding for murine FasL and the cationic liposome GL#67:DOPE. Six hundred and sixty micrograms of DNA in 250 μl H₂O and 0.5 μmol GL#67 in 250 μl H₂O were diluted to 5 ml with saline solution. This emulsion (20 °C) was instilled retro‐gradely through the left pulmonary vein after flushing with LPD solution (20 ml, at 4 °C). Subsequently, the graft was stored at 10 °C for 3 h. A single dose of cyclosporine A (CsA; 2.5 mg/kg i. m.) was given to all groups 48 h after the transplantation. In group 1 (n = 6), FasL/GL#67 was instilled as described. In group 2 (n = 5), GL#67 was given without DNA. Group 3 (n = 5) animals received CsA only. Five days after transplantation, gas exchange was assessed after exclusion of the contralateral native lung (FiO₂ = 1.0). Grafts were flushed with saline solution and fixed in formaldehyde for histological evaluation. No statistical difference in gas exchange (PaO₂) between the two control groups 2 (6.4 ± 0.4 kPa) and 3 (7.4 ± 0.4 kPa) could be detected 5 days postoperatively (P = 0.9). In contrast, grafts transduced with FasL (group 1) had significantly better gas exchange on postoperative day 5 (PaO₂: group 1 37.0 ± 10.6 kPa vs group 2 6.4 ± 0.41 kPa; P = 0.002). Two animals in group 1 revealed no or only minimal improvement in gas exchange. Histologically, all lung specimen of all groups showed signs of acute rejection (A2). Leukocyte infiltrates, rated by two independent observers, were less severe in all group 1 animals. Liposome‐mediated FasL gene transfer at the time of harvest in combination with low‐dose CsA reduces acute rejection in four out of six animals in this model of rat lung allotransplantation.     

A rat model of chronic allograft liver rejection

INTRODUCTION: The aim of this study was to develop a rat model of chronic irreversible rejection, which is a major causes of late graft loss and retransplantation after orthotopic liver allotransplantation. METHODS: Allogeneic liver transplantation was performed in a rat combination of Dark Agouti (DA) to Brown Norway (BN). Group A was left without treatment, group B received cyclosporine' (CsA; 1 mg/kg/d) and group C, CsA (4 mg/kg/d). Animals were followed for 6 months. Liver tissue was harvested to construct a time course of histological changes after liver transplantation using histopathological and morphometric techniques. We compared the total histological score of rejection activity index and survival rates. RESULTS: In untreated animals, irreversible acute rejection developed, all animals died within 15 days. In the low-dose CsA group, all animals that survived more than 30 days developed moderate to severe manifestations of chronic liver rejection, with graft infiltration, ductular damage or proliferation, obliterative arteriopathy, and liver fibrosis. No apparent histological alterations were observed in group C. Survival analysis showed significant differences between the three groups. CONCLUSIONS: In the rat strain combination of DA --> BN with low-dose immunosuppression, early mild inflammation was followed by the development of chronic rejection.     

Application of laser Doppler velocimetry to lung transplantation

The relationship between healing of a bronchial anastomosis and regional blood flow was studied in adult mongrel dogs after allotransplantation of the left lung. Animals were divided into the following three groups according to the immunosuppressive regimen. Group A: no immunosuppressive treatment (n = 7); Group B: azathioprine (5 mg/kg/day) and prednisolone (2 mg/kg/day) (n = 4); Group C: cyclosporine (20 mg/kg/day) (n = 4). The mucosal blood flow was examined serially after transplantation with laser Doppler velocimetry (LDV) at the tracheal bifurcation of the recipient (1st LDV) and at the bifurcation of the upper lobe bronchus of the transplanted lung (2nd LDV). The LDV values were expressed as a ratio to the preoperative values at the same site. Healing of the bronchial anastomosis was also assessed macroscopically with a fiberoptic bronchoscope and microscopically. The 2nd LDV value of the animals in group A at 13 days after transplantation remained low (32.9 +/- 27.6%). The 2nd LDV value in group B, although not significantly different from group A, had recovered to the preoperative level by that time (93.7 +/- 23.4%). By contrast, the 2nd LDV value in group C remained significantly higher than that in group A (119.9 +/- 23.0%, P less than 0.05). The 1st and 2nd LDV values were reduced in animals having infection at the bronchial anastomosis, even those in groups B and C. Bronchial mucosal blood flow appeared to be affected by infection and rejection of the transplanted lung, and to correlate closely with the healing of the bronchial anastomosis. This LDV method is useful to evaluate bronchial mucosal blood flow in experimental, and possibly in clinical, fields.     

Histologic and hemodynamic investigation on canine lung allografts

Histologic and hemodynamic investigations were performed on 26 mongrel dogs that underwent left lung allotransplantation. All dogs received cyclosporin A and azathioprine as immunosuppressants and were divided into two groups. In the 10 Group I dogs, no preservation was performed and the animals were followed until death. The 16 Group II dogs were subdivided into two groups; Group II-A dogs received the transplantation after 7 hours preservation and Group II-B dogs received it after no preservation. All dogs in Group II were sacrificed within 14 days following the transplantation. Seven of the dogs in Group I survived for over 90 days. The major histologic findings of Group I were pneumonitis, fibrotic interstitial changes and pleural thickening. Atypical pneumocytes were observed in three dogs, however structural changes of the bronchioles, suggesting obliterative bronchiolitis, were obscure. In Group II, 75 per cent of the dogs demonstrated the histologic features of rejection and early rejection was seen in a few dogs. Under electron microscopy, vascular wall damage was indicated by swollen endothelial cytoplasm and disrupted basement membranes. Small lymphocytes accumulating around the vessels showed lymphoblastic figures with rich intracytoplasmic organellae. The mean pulmonary arterial pressure measured by right pulmonary artery (PA) occlusion was elevated just after the transplantation in Group II, but decreased on the 7th day. The mean PA was again elevated on the 14th day in those dogs in which diffuse mononuclear cell cuffing was demonstrated. We consider that the PA-occlusion test can be used for determining the degree of rejection.     

Histologic and hemodynamic investigation on canine lung allografts

Histologic and hemodynamic investigations were performed on 26 mongrel dogs that underwent left lung allotransplantation. All dogs received cyclosporin A and azathioprine as immunosuppressants and were divided into two groups. In the 10 Group I dogs, no preservation was performed and the animals were followed until death. The 16 Group II dogs were subdivided into two groups; Group II-A dogs received the transplantation after 6 hours preservation and Group II-B dogs received it after no preservation. All dogs in Group II were sacrificed within 14 days following the transplantation. Seven of the dogs in Group I survived for over 90 days. The major histologic findings of Group I were pneumonitis, fibrotic interstitial changes and pleural thickening. Atypical pneumocytes were observed in three dogs, however structural changes of the bronchioles, suggesting obliterative bronchiolitis, were obscure. In Group II, 75 per cent of the dogs demonstrated the histologic features of rejection and early rejection was seen in a few dogs. Under electron microscopy, vascular wall damage was indicated by swollen endothelial cytoplasm and disrupted basement membranes. Small lymphocytes accumulating around the vessels showed lymphoblastic figures with rich intracytoplasmic organellae. The mean pulmonary arterial pressure measured by right pulmonary artery (PA) occlusion was elevated just after the transplantation in Group II, but decreased on the 7th day. The mean PA was again elevated on the 14th day in those dogs in which diffuse mononuclear cell cuffing was demonstrated. We consider that the PA-occlusion test can be used for determining the degree of rejection.     

Successful bronchial revascularization in experimental single lung transplantation

It is the purpose of this paper to report our experience with bronchial artery revascularization in an experimental model of single lung transplantation in swine. Thirty-three large white pigs weighing 20-40 kg underwent left lung allotransplantation. In 24 animals, bronchial artery revascularization was attempted by anastomizing the aortic patch containing the bronchial artery orifice with the recipient descending aorta. Eight survivors were put to death on postoperative days 11-15; five animals were put to death or died on postoperative days 2-9; the other animals died intra-operatively or within a few hours. Preservation of left bronchial vascularization was achieved in all cases attempted, as documented by post-mortem injection of dye (methylene blue) or contrast medium. Five of the 8 animals surviving for 11-15 days showed diffuse graft hepatization, associated with diffuse vascular thrombosis. Whether this was caused by damage to the endothelium due to poor graft preservation or by rejection was unclear. In animals surviving for 11-15 days without gross lung pathology, the anastomosis and bronchial mucosa were completely normal; in contrast, bronchial ischaemic changes were found in nonrevascularized animals and in survivors with graft hepatization. Our experience confirms that re-anastomosis of the bronchial arteries can prevent bronchial healing problems in single lung transplantation. The pig is an ideal model for these experiments since the bronchial arteries have a constant common aortic origin, allowing easy identification and preservation of left bronchial vascularization.     

大鼠肾上腺移植的实验研究

目的 观察大鼠同种异体肾上腺移植的效果及环孢素A（CsA)对其的作用。方法 采用显微外科技术进行大鼠同种异体带蒂肾上腺移植,对假手术组、双侧肾上腺切除组、纯系大鼠肾上腺移植组、异系大鼠肾上腺移植组及移植术后用CsA治疗组在血、尿醛固酮值,存活期及病理方面进行比较。结果 异系大鼠肾上腺移植后存在显著的排斥现象,术后口服CsA可明显延长大鼠存活期。结论 CsA能延长大鼠肾上腺移植的存活期,但CsA在大鼠肾上腺移植中应用的最佳时间及副作用有待进一步研究。     

FK506与CsA在肾移植术后抗排斥的临床应用

目的 比较他克莫司(FK506)与环孢素A(CsA)预防肾移植术后排斥反应的效果和安全性。方法 肾移植患者53例分成两组,FK506组为28例,CsA组为25例。其中CsA组因肝功能损害3例,难治性急性排斥反应1例而改换成FK506。FK506起始用0.2mg·kg~(-1)·d~(-1),CsA起始用6mg·kg~(-1)·d~(-1),同时分别联合应用MMF0.75g,每日2次口服,以及术后三天大剂量甲基强的松龙(MP)静滴,第三天改强的松口服,所有病例均严密观察并行血、尿等生化分析。结果 FK506组移植肾功能好,平均7.5天脱酐水平降至平均99.5μmol/L,2例出现排斥反应,经MP连续3d冲击后治愈。CsA组19例移植肾功能良好,6例出现急性排斥,其中3例经MP连续3d冲击后治愈,2例应用OKT3后急性排斥逆转,1例术后3d出现急性排斥经MP与OKT3治疗后改换成FK506,另3例肝损害呈进行性转氨酶升高改换成FK506。FK506组有血糖升高6例(18.8%),高血压5例(15.6％),感染7例(21.9％)。CsA组血糖升高2例(9.5％),高血压5例(23.8％),感染4例(19.0%)。结论肾移植术后应用FK506疗效确切,能有效防治难治性排斥的发生、发展,降低急性排斥的发生率,特别是在乙肝抗原阳性、肝功能受损者比CsA优越。     

Cyclosporine absorption in intestinal transplantation

The absorption of oral cyclosporine (CsA) was studied in a canine small intestinal transplantation model. Absorption of CsA was almost absent in bowel-resected dogs. Autotransplanted dogs showed a persisting malabsorption of CsA (mean peak of 687 +/- 348 ng/ml vs. 1683 +/- 154 ng/ml in control dogs). Allotransplanted dogs with normal graft histology showed a similar malabsorption (mean increase in CsA level: 833 ng/ml), whereas allotransplanted dogs with rejection of the graft showed a markedly decreased absorption (mean increase: 368 +/- 31 ng/ml). In two autotransplanted dogs pretreated with olive oil alone, CsA absorption increased over four weeks to a mean peak of 2215 +/- 5 ng/ml. We conclude that oral CsA is absorbed through the small intestine. Absorption of CsA is decreased after autotransplantation and allotransplantation, and rejection of the graft impedes it further. Regular administration of olive oil alone enhances absorption of oral CsA in a canine model.     

Xenograft survival in two species combinations using total-lymphoid irradiation and cyclosporine

Total lymphoid irradiation (TLI) has profound immunosuppressive actions and has been applied successfully to allotransplantation but not xenotransplantation. Cyclosporine (CsA) has not generally permitted successful xenotransplantation of organs but has not been used in combination with TLI. TLI and CsA were given alone and in combination to rats that were recipients of hamster or rabbit cardiac xenografts. Combined TLI and CsA prolonged survival of hamster-to-rat cardiac xenografts from three days in untreated controls to greater than 100 days in most recipients. TLI alone significantly prolonged rabbit to rat xenograft survival with doubling of survival time. However, combined treatment did not significantly prolong rabbit-to-rat cardiac xenograft survival compared with TLI alone. The hamster and rat are phylogenetically closely related. Transplants from hamsters to rat are concordant xenografts since the time course of unmodified rejection is similar to first-set rejection of allografts. Although the rabbit-to-rat transplant is also between concordant species (average survival of untreated controls: 3.2 days) the rabbit and rat are more distantly related. These results suggest that TLI is an effective immunosuppressant when applied to cardiac xenotransplants in these animal models; that the choice of species critically affects xenograft survival when TLI and/or CsA are used for immunosuppression; and that the closely related species combination tested has markedly prolonged (greater than 100 days) survival using combined TLI and CsA.     

Aerosolized cyclosporine as single-agent immunotherapy in canine lung allografts

Current systemic immunosuppressive regimens are unable to prevent lung allograft rejection consistently and are associated with significant morbidity and death. Acute rejection has occurred in 40% and chronic rejection in 50% of our lung recipients. We hypothesized that regional immunotherapy with aerosolized cyclosporine would prevent or reduce lung allograft rejection while allowing for low systemic drug delivery. In a canine model of unilateral lung allotransplantation, aerosolized cyclosporine was delivered directly to the allograft. Acute rejection was prevented or reduced in all treated recipients. All control animals had severe acute rejection. Intragraft cyclosporine concentration was high and systemic drug delivery was low, as evidenced by low whole-blood cyclosporine levels and low tissue cyclosporine levels in skeletal muscle. Ninety-five percent of whole-blood trough cyclosporine levels were less than 150 ng/ml. Aerosolized cyclosporine was able to prevent or reduce acute pulmonary rejection and resulted in minimal systemic drug delivery.     

Composite Tissue Vasculopathy and Degeneration Following Multiple Episodes of Acute Rejection in Reconstructive Transplantation

Transplant vasculopathy has not been systematically investigated in composite tissue allotransplantation (CTA). The impact of multiple acute rejections (ARs) on long‐term graft outcomes in reconstructive transplantation remains unknown. This study in a rat hind‐limb allotransplantation model systematically analyzes vasculopathy and tissue‐specific pathological changes secondary to multiple AR episodes. LEW rats were transplanted with BN rat hind limbs and treated as follows: Group 1 (Iso): isografts. Group 2 (CsA): Cyclosporine (CsA) qd; Group 3 (mult AR): CsA and dexamethasone only when AR was observed. No AR was observed in Groups 1 and 2. Multiple AR were observed in Group 3, and each episode was completely reversed (clinically) with pulsed CsA + dexamethasone treatment. Group 3 animals demonstrated significant vascular lesions along with skin and muscle atrophy, upregulation of profibrotic gene expression and fibrosis when compared to Groups 1 and 2. In addition, allograft bone was sclerotic, weak and prone to malunion and nonunion. Interestingly, vasculopathy was a late finding, whereas muscle atrophy with macrophage infiltration was seen early, after only a few AR episodes. Taken together, multiple AR episodes lead to vasculopathy and tissue‐specific pathology in CTA. This is the first evidence of ‘composite tissue vasculopathy and degeneration (CTVD)’ in CTA.     

大鼠脾移植诱导特异性免疫耐受效果

目的 比较异位脾移植和原位脾移植诱导特异性免疫耐受的效果.方法 建立大鼠异位脾移植和原位脾移植模型6周后,二期行同源心脏移植,比较移植心脏的存活时间和移植5d后的排斥反应强度.以单纯心脏移植组和心脏移植+环孢菌素组作为对照组.结果 移植心脏存活时间:心脏移植+环孢菌素组＞原位脾移植组＞异位脾移植组＞单纯心脏移植组(P＜0.05).术后第7天排斥反应强度和混合淋巴细胞反应强度测定:心脏移植+环孢菌素组＜原位脾移植组＜异位脾移植组＜单纯心脏移植组(P＜0.05).结论 由于脾脏的生理功能与门静脉系统的回流特点有关,较之于异位脾移植,原位脾移植能更为有效地诱导受体特异性免疫耐受状态.     

Extension of composite tissue allograft survival across major histocompatibility barrier under short course of anti-lymphocyte serum and cyclosporine a therapy

In this study, the authors investigated the effects of combined use of cyclosporine A (CsA) and anti-lymphocyte serum (ALS) on the survival of rat hindlimb allografts across a fully allogeneic major histocompatibility complex (MHC) barrier between Brown-Norway rats (BN, RT1 n) and Lewis rats (LEW, RT1 l). Thirty transplantations were performed in five groups of six rats each: Group 1 was the isograft control; Group 2 was the allograft control; Group 3 received ALS, Group 4 received CsA, and Group 5 received CsA and ALS. Treatment was started 2 hr before surgery and was then given for 21 days. Donor-derived chimerism was monitored by FACS analysis. Survival time was calculated as the number of post-transplant days until the first signs of rejection. The allografts in Group 2, Group 3, and Group 4 survived a mean of 5, 6, and 33 days, respectively. The longest mean survival time-51 days-was noted in Group 5 (p<0.05). Donor- derived chimerism peaked at 17 percent and fell to 0 percent at the time of rejection. A combined protocol of ALS/CsA extended survival of rat hindlimb allografts across a fully allogeneic MHC barrier.