心肺联合移植一例

心肺联合移植一例吴清玉朱晓东宋云虎丁素秋苏业璞景吉林１９９４年９月１日阜外医院与河北省人民医院协作，为１例１９岁女性先天性心脏病、室间隔缺损、肺动脉高压、艾森曼格综合征患者施行了心肺联合移植手术。手术顺利，术后存活１５天。现将此例心肺移植经验教训报告...     

心肺联合移植一例报道

2003年7月24日，我院成功地为1例先天性心脏病、房间隔缺损、肺动脉高压、艾森曼格综合征患者施行了同种心肺联合移植术(CHLT)。患者至今存活9月余，心功能Ⅰ级，活动正常。现将此例心肺联合移植报道如下：     

心肺联合移植后长期存活一例报告

目的 总结心肺联合移植的体会.方法 2006年3月23日对1例患有先天性室间隔缺损合并艾森曼格综合征的27岁女性患者施行了心肺联合移植术.术后对患者进行了长期密切监护,采用达利珠单抗进行免疫诱导,以他克莫司(后转换为环孢素A)、霉酚酸酯及糖皮质激素预防排斥反应,并严密监测和控制感染.结果 患者术后恢复顺利,未发生严重感染和急性排斥反应,术后109 d痊愈出院.术后1年7个月时,患者自行停用所有免疫抑制剂,2周后出现发热和活动后气促症状,行心脏彩色B型超声波、胸部CT、纤维支气管镜等检查,未发现排斥反应的特异性改变,肺功能检查显示第1秒最大呼气量为0.54,根据患者症状仍高度怀疑移植肺发生排斥反应,给予甲泼尼龙冲击治疗3 d,然后以泼尼松持续治疗1个月,维持血环孢素A浓度为0.1664～0.3328 μmol/L(0.2～0.4 mg/L),霉酚酸酯用量由0.5 g/d调整到1 g/d,同时行抗感染治疗,2周后患者症状消失.术后2年时,行纤维支气管镜肺活检,未见闭塞性细支气管炎综合征.术后2年5个月时,冠状动脉造影检查显示冠状动脉无狭窄,检测心功能正常.至2009年5月,患者已存活3年余.结论 重视供、受者的HLA配型,合理有效的预防排斥反应方案和感染的有效控制是心肺联合移植术成功的关键.     

心、肺联合移植一例报告

目的对1例心、肺联合移植术进行总结分析。方法对1例患先天性心脏病、室间隔缺损合并艾森曼格综合征者施行同种异体原位心、肺联合移植术,手术在中低温、体外循环下进行。术后对受者进行密切监护,积极防治排斥反应和感染。结果术中体外循环时间240min,升主动脉阻断时间125min;患者术后第7、203d发生移植肺急性排斥反应,第177、228d发生移植心急性排斥反应,均经治疗逆转;第9d发生肺部及胸腔感染,经抗感染治疗痊愈;第265d发生肺部毛霉菌感染,经两性霉素B治疗后症状控制;目前受者的心功能为Ⅰ级,超声心动图提示心脏结构及瓣膜功能基本正常,肺部感染的临床表现基本消失,生活自理。结论良好的心肺保护、细致的外科操作和正确的围手术期处理是心、肺联合移植成功的关键。     

心肺联合移植的应用进展

心肺联合移植是治疗终末期心肺功能衰竭的有效方法,现就心肺联合移植的进展作如下综述.一、心肺联合移植的历史及现状首例临床心肺联合移植于1968年由Cooley等实施.1981年Reitz等首先将环孢素A(CsA)用于心肺联合移植,并获得良好的效果.截至2009年6月,据国际心肺移植协会(ISHLT)统计,全世界已完成3575例心肺联合移植,然而受供者短缺的限制,目前世界范围内心肺联合移植的规模正逐年缩小.1982年1月到2007年6月全世界共施行心肺联合移植超过2500例,2005-2009年的年心肺联合移植例数分别为86、80、85、75、73[1].随着心肺联合移植外科技术的进步以及新型免疫抑制剂和抗感染药物的应用,受者3个月的存活率由开展初期的70.7％提高到目前的81.7％,但远期疗效仍不甚理想,ISHLT和移植受者科学登记系统( SRTR)登记全球心肺联合移植受者的1年存活率分别为80.6％、72.9％,5年存活率为61.7％、51.6％,而10年存活率均在29％左右[2].目前已有心脏移植后存活时间超过20年的病例报道[1].     

心肺联合移植11例单中心经验

目的总结心肺联合移植经验。 方法回顾性分析2015年9月至2018年11月广州医科大学附属第一医院完成的11例心肺联合移植受者临床资料。男性7例,女性4例,平均年龄(32±11)岁。原发病为艾森曼格综合征3例,特发性肺动脉高压4例,复杂先天性心脏合并肺血管病变、肺动脉栓塞、双肺移植术后心肺功能衰竭及扩张型心肌病合并慢性阻塞性肺疾病各1例。供者选择参照肺移植及心脏移植标准。11例受者均采用胸骨正中切口,经主动脉和上、下腔静脉远端插管建立体外循环,切除受者心肺后,植入供肺和供心,依次吻合气管、主动脉、上腔静脉及下腔静脉。 结果11例受者中,4例术后30 d内死亡,其中2例死于胸腔及纵隔出血,2例死于脑血管并发症;术后30 d至1年死亡3例,死因为排斥反应引起的移植物功能障碍及感染、移植物功能障碍导致的多器官功能衰竭。术后1年有4例受者存活。 结论严格选择供、受者以及术中后纵隔彻底止血可显著降低心肺联合移植手术死亡率,提高受者术后生存率及生存时间。     

心肺移植3例

目的 总结3例心肺移植的经验.方法 2003年7月至2012年8月,3例终末期心肺疾病患者施行心肺移植手术.1例先天性房间隔缺损伴艾森曼格综合征,心功能Ⅳ级；1例扩张性心肌病伴中重度肺动脉高压,心功能Ⅲ～Ⅳ级；1例左心室双出口合并室间隔缺损伴肺动脉主干及左、右分支狭窄,心功能Ⅲ～Ⅳ级.心肌保护液均为UW液；肺保护液均加入前列腺素E1,Euro-Collin液1例,低钾右旋糖酐液2例.术前给予赛尼派或巴利昔单抗、术中甲基泼尼松龙、术后环孢素/他克莫司+泼尼松+骁悉抗排斥治疗.术中严密止血.移植术后严格消毒、隔离,加强呼吸道护理.例2患者术毕至术后31天胸液量14 640ml,术后40天内应用纤维支气管镜吸痰13次,同时使用广谱抗生素及抗真菌药物控制感染.结果 3例患者全部痊愈出院.1例术后4年10个月因慢性排异反应引起的阻塞性支气管炎、肺功能衰竭死亡；1例术后68天因突发脑血管意外死亡；1例目前健在,已生存1年余.结论 妥善保护心肺功能,术中认真止血,手术操作精细,术后加强防治感染,重视应用纤维支气管镜和合理的抗排斥治疗是心肺移植成功的重要因素.     

心肺移植术中对心肺保护的体会

目的总结室间隔缺损合并艾森门格综合征(Eisenmengersyndrome)患者施行心肺移植术的经验。方法2003年6月25日为1例先天性室间隔缺损合并艾森门格综合征患者施行心肺移植术,采用改良St.Thomas号液保护心肌和Euro-Collins液保护肺。结果术中供者心肺保护良好,术后受者血流动力学稳定,呼吸功能恢复较快,现已生存500d,生活质量良好。结论术中良好的心肺保护、术后防治并发症是提高心肺移植生存率的重要因素。     

心肺联合移植的手术适应证及结果

自1981年世界首例心肺联合移植手术（heartlung transplant,HLT）在美国Stanford大学医学院附属医院实施并得以长期存活以来,第2例HLT手术是在1例艾森曼格综合征无法行心脏手术的先天性心脏病患者身上实施。     

心肺联合移植的麻醉经验

我院于 1999年 9月 2 7日为 1例先天性心脏病、室缺、艾森曼格氏综合征的患者施行了同种异体心肺联合移植术 ,手术获得成功。现报道如下。1.临床资料 :患者女性 ,2 3岁 ,体重5 0ｋｇ。活动性心慌、气喘 2 0余年 ,发绀10余年。心导管检查为右向左分流 ,重度肺动脉高压 (阻力性 ) ,压力为 10 5 / 6 7ｍｍＨｇ。供者为男性 ,2 4岁 ,脑死亡者 ,心肺正常。供、受者ＡＢＯ血型相同 ,检验细胞免疫、体液免疫均正常。2 .麻醉方法 :术前 1ｄ了解患者思想 ,做心理护理。术前 30ｍｉｎ清洁口腔、鼻腔 ,肌注吗啡 8ｍｇ、东莨菪碱0 .15ｍｇ。入室后建立 2…     

达利珠单抗联合环孢素A、霉酚酸酯及糖皮质激素预防肾移植后急性排斥反应

目的 观察达利珠单抗联合环孢素A、霉酚酸酯和糖皮质激素预防肾移植后急性排斥反应的有效性和安全性。方法 由15家肾移植中心参加的开放性临床试验，共纳入72例首次尸肾移植受者为研究对象，在接受环孢素A、霉酚酸酯和糖皮质激素联合应用预防肾移植后急性排斥反应的同时，给予2剂人源化达利珠单抗，首剂给予时间为术前24h内，第2剂在术后第14d给予。对入选患者密切随访，评价肾移植后3个月和6个月时急性排斥反应的发生率、严重程度以及人、肾存活率；评价该治疗方法的安全性。结果 术后3个月内有3例患者发生4次急性排斥反应，3个月及6个月的排斥反应发生率均为5．56％；人／肾6个月和1年的存活率分别为95.8％／95.8％和94．5％／94．5％；仅有1例的腹痛可能与达利珠单抗有关。结论 2剂达利珠单抗联合环孢素A、霉酚酸酯和糖皮质激素预防肾移植后的急性排斥反应安全有效。     

Clinical experience in the management of pulmonary opportunist infection and rejection in recipients of heart-lung transplants.

The main clinical problems that follow heart-lung transplantation are opportunist infections of the lungs and pulmonary rejection. Of 23 patients undergoing heart-lung transplantation, eight had opportunist infections and 12 had at least one episode of pulmonary rejection. Cardiac rejection occurred in only one patient, who did not need treatment. Of the 12 patients who had pulmonary rejection, nine recovered fully after augmented immunosuppression with high dose corticosteroids, although one patient required additional low dose corticosteroids for eight months before making a full recovery. Fatal opportunist lung infection followed treatment for rejection in two patients. One patient developed obliterative bronchiolitis. Of the eight patients with opportunist infections, five had primary cytomegalovirus pneumonitis, acquired from the donor. All three patients treated with acyclovir died, whereas the two treated with hyperimmune globulin and dihydroxy proxymethylguanine recovered fully. Two patients developed Pneumocystis carinii pneumonia, which was treated successfully in one patient with intravenous sulphadimidine and trimethoprim. The other patient died after a further episode of rejection and aspergillus bronchitis. One patient developed a tuberculous empyema. The calculated actuarial survival at one year was 78% and at two years 67.2%. Although it is still in its innovative stage heart-lung transplantation appears to have complications and results similar to those of transplantation of other organs.     

Diagnosis and treatment of allograft rejection in heart-lung transplant recipients

Six patients received heart-lung transplants between March, 1981, and January, 1982. There were four women and two men between 26 and 45 years of age, three with primary pulmonary hypertension and three with congenital heart disease and pulmonary hypertension (Eisenmenger's syndrome). Immunosuppression was primarily with cyclosporin-A, with additional corticosteroid, azathioprine, and rabbit antihuman thymocyte globulin. Six episodes of allograft rejection in four patients (10, 11, 21, 24, 53, and 86 days after transplantation) were detected by means of transvenous endomyocardial biopsy. All patients experienced pulmonary edema early after transplantation (reimplantation response), and two patients required mechanical ventilatory support for allograft rejection at 10 and 11 days. Treatment of rejection consisted of intravenous methylprednisolone (four episodes) or augmented oral prednisone (two episodes), with resolution. No episode thought to be pulmonary rejection has occurred in the absence of cardiac findings. Four patients are alive from 6 to 15 months after transplantation and are functionally normal. Early experience with heart-lung transplantation suggests (1) that allograft rejection can be detected by cardiac findings and successfully treated by augmented corticosteroids, (2) that lung rejection does not occur in the absence of cardiac findings, (3) that the frequency and severity of rejection episodes are not greater than with standard cardiac transplantation, and (4) that the frequency of rejection episodes is highest within the first 60 days after transplantation.     

单肺移植同期行心内缺损修补术一例

目的探讨同种异体单肺移植同期行心内缺损修补治疗先天性心脏病室间隔缺损并艾森曼格综合征的可行性及围手术期的处理。方法2004年10月22日为1例先天性心脏病室间隔缺损合并艾森曼格综合征的患者在全麻低温体外循环下行右侧单肺移植，同期行室间隔缺损修补术。术中体外循环时间244min，供肺冷缺血时间6h。术后用他克莫司、霉酚酸酯和激素三联免疫抑制治疗。结果术后3d内移植肺出现中等度移植反应性肺水肿，术后7d气管切开，术后12d撤离呼吸机；术后14d出现急性排斥1次，治疗后缓解。术后肺动脉压力由术前的110／60mmHg降到53／39mmHg。术后30d胸片及胸部CT显示右侧移植肺清晰；肺通气／血流灌注扫描示右侧移植肺血流占90％；超声心动图检查示左心室内径较术前缩小17％，室间隔缺损修补完整，无残余分流；术后活动耐力明显改善，62d出院。结论对终末期左向右分流的先天性心脏病实施同种异体单肺移植的同期行心内畸形矫治是可行的。良好的供肺切取和保护以及完善的术后处理是成功的关键。     

Single lung transplantation with cyclosporin immunosuppression. Evaluation of canine and human recipients

Cyclosporin, a potent new immunosuppressive agent, was used (alone or in combination with other drugs) in 28 canine single lung allograft recipients. Mean recipient survival with good allograft function was 155 days with cyclosporin and far exceeded that obtained in previous single lung allograft recipients treated with standard immunosuppression (15 to 22 days). The results of these experiments were as follows: (1) 20% of the recipient animals exhibited no evidence of rejection whatsoever; (2) four of 28 animals survived more than 350 days with good allograft function; (3) 79% of the animals exhibited some evidence of rejection that was easily reversed in 74% of instances with corticosteroids; (4) 10 of 28 animals exhibited good lung allograft function 5 months or more after operation; (5) in cyclosporin-treated lung allograft recipients, rejection was diagnosed by the presence of infiltrate on chest roentgenogram, analysis of the cellular content of bronchoalveolar lavage samples, and decreased perfusion on 99mtechnetium lung scan; (6) complete healing without stenosis of the bronchial anastomosis occurred in 82% of the animals studied. One of two patients treated with cyclosporin after undergoing single lung allografting survived 7 weeks after transplantation and 4 weeks after contralateral pneumonectomy. Episodes of rejection were reversible, and the bronchial anastomosis healed normally. This overall experience indicates that cyclosporin, although not a perfect immunosuppressive agent, increases the likelihood of success with therapeutic single lung transplantation.     

肝胰肾联合移植的免疫抑制治疗

目的 介绍1例存活超过1年的肝胰肾联合移植患者术后免疫抑制治疗方法。方法对1例肝炎后肝硬化合并尿毒症、I型糖尿病、慢性胰腺炎患者施行原位背驮式肝、胰液空肠引流式胰、十二指肠及肾一期联合移植，采用二剂巴利昔单抗（舒莱）诱导，抗胸腺细胞球蛋白（ATG）、他克莫司（FK506）、吗替麦考酚酯（MMF）、泼尼松四联维持治疗。结果 术后移植肝脏及胰腺功能1周内逐渐恢复；肾功能延迟恢复，于术后第16天因消化道大出血致肾脏血流下降，切除移植肾脏，于原移植部位进行第2次肾移植，术后第3天肾功能恢复正常，未发生排斥反应。患者已健康存活超过1年，移植肝、胰、肾功能良好，生活自理。结论 肝胰肾联合移植术前后采用二剂舒莱诱导，同时用ATG、FK506、MMF及泼尼松作为免疫维持治疗安全有效，用药期间进行移植物功能、血药浓度及T细胞亚群（CD4^＋，CD4^＋）监测是防治排斥反应、感染及药物中毒的有效手段。     

Cellular allograft rejection affecting the donor aorta after combined heart-lung transplantation

BACKGROUND: Infectious pseudoaneurysms of the ascending aorta are a recognized major complication after heart-lung transplantation. METHOD: This report describes an unusual and previously unreported complication, that of cellular allograft rejection, which caused a pseudoaneurysm of the donor's ascending aorta in a patient who underwent combined heart-lung transplantation. Repair was performed by primary suture after mobilization of the aortic segments. RESULT: On histological examination the resected aneurysm showed evidence of proliferative vasculitis with perivascular infiltration of the vasa vasorum by mononuclear cells. The mononuclear cells were identified as CD4+ and CD8+ by immunohistological staining. CONCLUSIONS: This report shows that cellular allograft rejection may affect the donor aorta after heart-lung transplantation and may result in pseudoaneurysm formation, even under triple-drug immunosuppression after ABO-compatible allograft transplantation.     

Trimethoprim-sulfamethoxazole prophylaxis for Pneumocystis carinii infections in heart-lung and lung transplantation--how effective and for how long?

Pneumocystis carinii pneumonia (PCP) is a common clinical problem in the setting of organ transplantation, particularly in heart-lung and lung allograft recipients. Without prophylactic measurements, the incidence of P carinii pneumonia can reach up to 88% of heart-lung transplant recipients. We conducted a retrospective analysis of the Stanford heart-lung and lung transplant experience in order to assess the efficacy of the prophylactic therapy and to try to define the duration of therapy necessary for prevention. During a 9-year period 82 heart-lung and 13 single-lung transplants were performed. Of the patients not on prophylaxis therapy 27% (13 patients) developed P carinii infection as compared with 0% of patients on trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. The incidence of PCP infection peaked between 3 and 6 months posttransplantation. No case of infection was observed before the 7th week posttransplant. PCP was more common following induction immunosuppression with OKT3 as compared with RATG (P less than 0.05). All cases of infections later than one year posttransplant were associated with recent increase in the immunosuppression regimen with high-dose corticosteroids for treatment of acute or chronic (obliterative bronchiolitis) rejection. Although our study is retrospective and based on various immunosuppressive and diagnostic technique periods, it seems that TMP-SMX is highly effective in preventing PCP infections in heart-lung and lung transplant recipients. Twelve months of therapy is probably a sufficient length of therapy if immunosuppressive therapy is stable. However, whenever augmentation in the immunosuppression regimen is indicated, prophylactic therapy should promptly be restarted.     

Lung and heart-lung transplantation in patients with end-stage cystic fibrosis: the Stanford experience

BACKGROUND: Bilateral lung (BLTx) and heart-lung transplantation have gained wide acceptance as treatment of end-stage lung disease from cystic fibrosis. We reviewed our 13-year experience with thoracic transplantation for cystic fibrosis with an operative approach that favors use of cardiopulmonary bypass for BLTx. METHODS: Sixty-four patients with cystic fibrosis underwent heart-lung transplantation (n = 22, 34.4%) or BLTx (n = 42, 65.6%) between 1988 and 2000. Mean age and weight at transplantation were 29 +/- 8 years and 51 +/- 11 kg, respectively. Mean follow-up for survivors was 4.4 +/- 3.6 years. Immunosuppression regimen included cyclosporine, tapered corticosteroids, azathioprine, and induction therapy with OKT3 (murine monoclonal antibodies) or rabbit antithymocyte globulin. Cardiopulmonary bypass was used in all but 5 patients (7.8%). However, in 8 (19%) of the 42 patients having BLTx, only the grafting of the second lung was performed with cardiopulmonary bypass. RESULTS: The operative mortality rate was 1.6%. The actuarial survival rates at 1 year, 3 years, 5 years and 10 years were 93.2%, 77.7%, 61.8%, and 48.1%, respectively, with no significant difference between BLTx and heart-lung transplantation. The major hospital complications were pneumonia (n = 11, 17.2%) and bleeding (n = 8, 12.5%). Clinically significant reperfusion injury was observed in 6 patients, 3 of whom required reintubation. Freedom from acute lung rejection beyond 1 year was 47.7%. One patient underwent late retransplantation, and 4 required bronchial stenting. Obliterative bronchiolitis accounted for eight (50.0%) of 16 late deaths. CONCLUSIONS: Though postoperative bleeding and pneumonia are still of concern, satisfactory early and intermediate-term results can be expected in patients undergoing BLTx or heart-lung transplantation for cystic fibrosis. Cardiopulmonary bypass can be used for BLTx with no adverse impact on intermediate and long-term outcomes.