心肺联合移植中供者心、肺的保护及术后排斥反应的诊断和治疗二例

目的 探讨心肺联合移植中供者心、肺的保护措施,以及术后免疫抑制方案、排斥反应的临床诊断及其处理.方法 回顾分析2例心肺联合移植的临床资料.2例供肺的灌洗分别使用Perfadx保护液(每1000 ml加入氨基丁三醇0.3 ml,伊洛前列素25 μg)和Euro Collins(EC)保护液(每1000 ml加入氨基丁三醇0.3 ml,前列地尔100 μg).供心的灌洗使用UW液.心肺联合移植采用经典原位技术.免疫抑制方案采用巴利昔单抗诱导,术后采用环孢素A+吗替麦考酚酯+皮质激素.术后早期观察受者的血象变化,各器官功能,各心腔大小及室间隔、左室后壁厚度等,必要时行胸部CT、纤维支气管镜及组织病理检查,及时发现排斥反应征象.受者发生排斥反应后给予皮质激素冲击治疗,并及时调整免疫抑制剂用量.结果 2例受者分别于术后第80天和第141天康复出院,分别随访4年6个月与4年2个月,现生活质量良好.1例受者于术后第10天和第26天发生急性排斥反应,另1例受者于术后第29天和第87天发生急性排斥反应,均经皮质激素冲击治疗,并调整免疫抑制剂用量后逆转.当受者发生急性排斥反应时,往往伴有血象的变化及室间隔和左心室后壁厚度的增加,给予相应治疗后渐恢复至正常范围.结论 Perfadx保护液和EC保护液对供肺均有较好的保护作用,UW液对供心有较好的保护作用;术后及时发现排斥反应与感染,并采取恰当的处理措施有利于受者顺利康复.

Abstract：

Objective To summarize the preservation measures of the donor's heart and lung, and the postoperative immunotherapy, as well as the clinical experience of discrimination and management for graft rejection.Methods The clinical data of 2 cases of heart-lung transplantation in our department were retrospectively analyzed. Two different protective liquids were used for donor's lung lavage of 2 cases: Perfadx solution (1000 mL containing tris 0.3 mL and ilomedin 25 μg); Euro Collins solution (1000 mL containing tris 0.3 mL and PGE1 100 μg). UW solution was used for donor's heart lavage. Surgical procedure for heart-lung transplantation was classic technique in situ. The schedule of immunosuppression was induced by Basiliximab, and combined with cyclosporine+ mycophemolate mofeil+corcal hommone after operation. recipient's blood count, organ's functions, the sizes of every cavity of heart, IVSPW and LVPW were observed during early post-operation. The recipients were subjected to chest CT scan, fiberoptic bronchoscope and tissue pathological study when necessary to find the signs of rejection promptly. When the rejection occurred in the recipient, cortical hormone's impulse therapy was given and the dose of immunosuppression was adjusted in time.Results Two patients discharged in 80 days and 141 days after operation. The patients were followed up for 54 months and 50 months respectively, and their life qualities were very well. Acute rejections occurred on the 10th and 26th day in one case, and in another case, acute rejections occurred on the 29th and 87th day after operation. All were conversed by cortical hormone's impulse therapy and adjusting the dose of immunosuppressants. When acute rejection occurred, the blood count had significant change, and IVSPW and LVPW were increases. They were returned the normal range after corresponding therapy.Conclusion Perfidx solution and Euro-Collin solution may play good protective roles for donor's lungs. UW solution may play good a protective role for donor's heart. To discriminate the clinical graft rejection and infection in time and administrate correct management will have large benefits for the patients' rehabilitation.     

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.     

异种移植诱导免疫耐受策略的研究进展

异种移植时由于需要克服强有力的免疫排斥反应，免疫抑制剂的大量应用带来的危险性远远超过了同种器官移植，因此目前认为只有诱导人体对动物器官产生特异性的免疫耐受，异种移植才有可能走向临床。本文就近年来诱导供者特异性免疫耐受的策略研究进展进行了综述。     

移植小肠黏膜的组织学观察五例

目的 探讨移植小肠黏膜的形态学改变规律,以对小肠移植后急性排斥反应(AR)的诊断和治疗提供可靠的依据.方法 对5例小肠移植受者术后324个肠黏膜活检样本进行组织学和组织化学检查,并在电镜下观察.结果 5例移植后的肠黏膜组织学改变基本一致,均先后经历再灌注损伤、淋巴回流恢复、AR、肠功能改变等过程.术后0～3个月间3例发生移植肠黏膜活检病理学诊断为不确定(IND)级至轻度(1级)AR4次,术后3～6个月2例发生IND级至1级AR3次,术后7～12个月2例发生中度(2级)AR 4次,重度(3级)AR 2次.AR的一般形态学改变包括移植肠黏膜结构改变、隐窝上皮损伤、炎症细胞浸润等.结论 小肠移植后肠黏膜活检是监测AR比较可靠的手段,连续动态地观察可以有效地监测术后AR的发生、发展以及评价治疗效果.对于AR须进行综合性诊断,单一形态学改变不具备特异性.移植肠超微结构改变对判断黏膜屏障功能及确定病原微生物有帮助.     

小肠移植的现状

1 小肠移植的概况 1964年美国的Deterling首次施行人小肠移植2例,但均因排斥反应分别于术后12h和2d切除坏死小肠.到1972年以前,全世界共施行8例,其中1例存活6个月,其余均未超过1个月.     

羟乙基淀粉对兔心肺联合保存的作用

羟乙基淀粉对兔心肺联合保存的作用邱罕凡廖崇先陈道中应用Ｋａｎｅｋｏ兔异位心肺移植模型〔１〕，在晶体心肺保存液中添加５％羟乙基淀粉（ＨＥＳ）以研究胶体物质ＨＥＳ对兔心肺联合保存的作用及机制。现报告如下：材料和方法同品种、同饲养条件，体重２．０～２．５ｋ...     

亲属活体小肠移植后急性排斥反应的监测与治疗一例

目的探讨亲属活体小肠移植后急性排斥反应的监测与治疗。方法对1例短肠综合征患者施行亲属活体小肠移植，手术分两期进行。供者为患者的母亲，供、受者HLA有4个抗原相符。移植肠段长120cm，一期手术时供、受者肠道不进行吻合，移植肠两端在腹壁造口，一期手术后188d，再行二期手术，分别将受者残存小肠的近端、远端与移植肠袢的近端、远端作端侧吻合。术后观察移植小肠引流液的性状，定期内镜观察，并行移植肠组织学检查。采用他克莫司、霉酚酸酯及甲泼尼龙预防排斥反应，并予两剂达利珠单抗诱导。结果受者两次手术均顺利。一期手术后37d出现急性排斥反应，给予皮质激素冲击治疗9d，未能逆转，后改为莫罗单抗-CD3治疗8d后逆转。术后121d，肠镜及组织学检查证实移植肠修复良好，小肠绒毛形态及结构基本正常，D-木糖吸收试验提示移植肠吸收功能改善。现患者已存活213d，体重增加4．5kg，进半流质饮食，生活自理。结论小肠移植后可采取肠镜和组织学检查，并结合临床表现来综合判断排斥反应。发生急性排斥反应时，及时予以激素冲击治疗，无效时可用莫罗单抗-CD3。     

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。     

肺移植急性排斥反应的诊治(附三例报告)

目的观察和探讨肺移植急性排斥反应的临床表现、诊断方法、经支气管活检排斥反应的病理分类和治疗。方法2002年9月至2003年6月，分别为3例肺气肿、肺功能重度减损的患者进行了单肺移植。其中后2例为同一供者的左、右肺，第2例受者HLA无1个位点匹配。结果第1例左肺移植术后第9d发生1次急性排斥(A2b级)，经大剂量甲泼尼龙冲击治疗后症状消退；第2例右肺移植第7d持续发生急性排斥(A4c级)，经甲泼尼龙冲击并用OKT3治疗无效，术后第15d死亡；第3例左肺移植第9d、第15d发生2次急性排斥(A3a级)，经甲泼尼龙冲击并用OKT3治疗8d后缓解。结论选择组织相容性好的供、受者进行肺移植，是成功的保证。肺组织活检成为诊断急性排斥的金标准，对肺移植急性排斥反应的及时诊治是减少术后死亡率的关键。     

L-精氨酸对心肺移植缺血再灌注损伤的保护作用

目的探讨一氧化氮(NO)前体L-精氨酸(L-Arg)在心肺移植中对心肺缺血再灌注损伤的保护作用。方法将30条成年犬随机分为对照组、实验A(L-Arg 100 mg／kg体重)、B(L-Arg 500 mg／kg体重)3组,每组10条,采用标准法行心肺移植,A、B组心肺保护液中加入不同剂量L-Arg,供心肺放入4℃EC液保存4-5 h。监测心率、平均动脉压(MAP)、肺动脉平均压(MPAP),股静脉血一氧化氮(NO)、超氧化物歧化酶(SOD)、丙二醛(MDA)、心肌肌钙蛋白I(cTnI)、乳酸脱氢酶同工酶 (LDH)含量、股动脉血氧分压(PaO2),测定肺干湿重比(W／DR)及观察心肺超微结构以评价心肺保护的效果。结果主动脉开放60 min,B组NO(82．76±12．34)μmol／L、A、B组SOD(60．19±12．42)、 (100．38±16．55)NU／ml较对照组(29．43±12．42)μmol/L、(26．65±5．68)NU／ml高(P<0．05),B组 cTnI(11．07±2．62)mg／L、MDA(2．48±0．51)nmol／ml、LDH(592．8±51．92)U／L较对照组(23．16± 2．76)mg／L、(4．48±0．54)nmol／ml、(719．80±292．16)U／L低(P<0．05),B组PaO2(207．60± 32．72)mmHg(1 mm Hg=0．133 kPa)高于对照组(130．20±13．36)mm Hg(P<0．05),A、B组W／DR (84．82±1．14)％、83．84±1．63)％小于对照组(88．44±1．42)％(P<0．05),电镜检查A、B组心肺损伤轻于对照组。结论供心肺可安全保存4-5 h,在心肺移植实验中加入L-Arg可使NO含量增加, 减轻心肺缺血再灌注损伤,B组(500 mg／kg体重)效果更好。     

外源性肺表面活性物质对心肺联合移植供肺的保护作用

目的　通过在心肺联合移植过程中导入外源性肺表面活性物质 (PS) ,探索改善移植肺的肺功能 ,增加心肺联合移植的成功率。方法　应用改良的Kaneko兔异位心肺联合移植模型 ,分别在移植物切取后和供体再灌注后导入外源性PS ,观察实验组及对照组在 3 0、60、90、12 0min的动脉血气氧分压 (PaO2 )、二氧化碳分压 (PaCO2 )的变化 ,及移植后两组兔血浆内皮素 (ET 1)和髓过氧化物酶 (MPO)的变化 ,并观察移植肺组织的超微结构。结果　实验组中PaO2 值在各时间段分别 ( 12 .64± 4.47)、( 12 .5 8± 4.13 )、( 12 .46± 3 .85 )、( 12 .5 0± 3 .93 )kPa较对照组 ( 11.71± 5 .0 0 )、( 11.69± 4.2 2 )、( 11.5 9± 4.2 6)、( 11.5 6± 3 .93 )kPa明显升高 ,PaCO2 值在 60、90、12 0min( 4 .5 5±0 .5 3 )、( 4 .93± 0 .40 )、( 5 .65± 0 .65 )kPa较对照组 ( 5 .0 7± 0 .3 9)、( 5 .47± 0 .5 5 )、( 6.3 9± 0 .65 )kPa下降 ,ET 1( 4 .3 0± 0 .45 )ng/L和MPO( 3 .2 9± 0 .5 4)U/(mg·ml)均较对照组 [分别 ( 6.0 7± 0 .79)ng/L、( 7.70± 1.18)U/(mg·ml) ]显著下降 ,差异有显著性 (P <0 .0 5 ) ,移植肺的肺泡Ⅱ型细胞 ,Ⅰ型细胞损伤减小。结论　在心肺联合移植过程中导入外源性PS ,可改善移植肺的肺功能 ,     

供肝冷缺血时间延长诱发大鼠原位肝移植术后早期急性排斥反应的研究

目的 研究供肝冷缺血时间延长对大鼠原位肝移植术后早期急性排斥反应的影响.方法 选取30只健康纯系清洁级BN大鼠和30只Lewis大鼠.分别作为纯系移植和同种异体移植的供者,受者均为健康纯系清洁级BN大鼠60只,建立纯系和同种异体原位肝移植模型.根据纯系移植和同种异体移植供肝冷缺血时间的不同,将供、受者分为A、B、C和D组,每组15对.A组:供肝冷缺血1 h后进行纯系移植;B组:供肝冷缺血18 h后进行纯系移植;C组:供肝冷缺血1 h后进行同种异体移植;D组:供肝冷缺血18 h后进行同种异体移植.术后观察受者的2周存活率、移植肝组织病理学及肝功能的改变,检测受者主要组织相容性复合物(MHC)-Ⅱ类分子和核转录因子κB(NF-κB)的表达水平.结果 肝移植术后2周,A、B、C和D组的存活率分别为83.3%、66.7%、16.7%和0%,不管是纯系移植组还是同种异体移植组中供肝的冷保存时间越短,受者的存活率越高,且经肝功能检查发现冷保存时间短的受者移植肝功能恢复较好,移植肝组织病理学损伤和急性排斥反应也明显较轻.B组受者术后移植肝大量表达MHC-Ⅱ类分子,明显高于A组(P＜0.05);两同种异体移植组MHC-Ⅱ类分子的表达量较两纯系移植组增加明显,D组增加最多.A组几乎不表达NF-κB,而B组NF-κB的表达显著增加(P＜0.05);两同种异体移植组受者NF-κB的表达峰值提前.结论 冷缺血时间的延长可以诱导发生和加重大鼠原位肝移植术后早期急性排斥反应,降低术后2周存活率.     

Early graft function following heart and lung transplantation

Fifty-one patients underwent heart-lung transplantation between April 1984 and October 1988. The first five donor organs were removed in an adjacent operating theatre. Organs were subsequently removed from distant centres. The method of preservation consisted of cold cardioplegic arrest of the heart using St. Thomas' solution, followed by a simple, cold pulmonary artery flush of a lung perfusate developed at Papworth Hospital. Administration of the solution was preceded by an infusion of prostacyclin into the pulmonary artery during preliminary dissection of the donor organs. The total ischaemic time ranged from 48 to 51 min (mean 49.6 min) for the near procurement group and from 70 to 249 min (mean 154.2 min) for the distant procurement group. There were no primary organ failures. Function of the lungs was assessed by gas exchange, pulmonary function tests, time to extubation, and survival data. Serial radiological studies were used to monitor graft performance in the postoperative period. We report here on our clinical experience of early graft function following heart and lung transplantation.     

Early graft function following heart and lung transplantation

Abstract. Fifty-one patients underwent heart-lung transplantation between April 1984 and October 1988. The first five donor organs were removed in an adjacent operating theatre. Organs were subsequently removed from distant centres. The method of preservation consisted of cold cardioplegic arrest of the heart using St. Thomas' solution, followed by a simple, cold pulmonary artery flush of a lung perfusate developed at Papworth Hospital. Administration of the solution was preceded by an infusion of prostacyclin into the pulmonary artery during preliminary dissection of the donor organs. The total ischaemic time ranged from 48 to 51 min (mean 49. 6 min) for the near procurement group and from 70 to 249 min (mean 154. 2 min) for the distant procurement group. There were no primary organ failures. Function of the lungs was assessed by gas exchange, pulmonary function tests, time to extubation, and survival data. Serial radiological studies were used to monitor graft performance in the postoperative period. We report here on our clinical experience of early graft function following heart and lung transplantation.     

Long-term outcome of lung transplantation for cystic fibrosis — Danish results

Objective: Over the last decades improvements in medical therapies have delayed the progression of lung disease in cystic fibrosis (CF). However, lung disease is still the most common cause of premature death, and lung transplantation today is the only treatment for end-stage lung disease in patients with CF. We present a retrospective review of the outcome of CF patients transplanted in Denmark since start of the national lung transplantation programme in 1992. Methods: In a 10-year period, 47 patients with CF were listed for lung transplantation; 29 patients underwent transplantation and 18 patients died while waiting for donor organs. Eleven patients received en block double lung transplantation with direct bronchial artery revascularization and 18 patients received bilateral sequential lung transplantation. Median age at transplantation was 29 years (range 11–50). Results: The perioperative mortality (≤30 days) was 3.5% (1/29 patients). Actuarial survival of transplanted patients at 1, 3, 5 and 8 years was 89, 80, 80 and 70%, respectively. Actuarial survival of non-transplanted patients on the waiting list at 1 and 2 years was 28 and 11% (P<0.0001). Causes of death of transplanted patients were: respiratory failure on day 7 (n=1), bronchiolitis obliterans syndrome (n=2), infection (Cytomegalovirus, Aspergillus fumigatus) (n=2), bronchial anastomosis dehiscence (n=1). Pulmonary function (FEV₁% predicted) improved from median 20% (range 13–31) pre-transplant to 71% (range 19–118) after 5 years (P<0.0001). Renal function (⁵¹Cr-EDTA clearance) decreased from median 97 ml/min (range 45–190) pre-transplant to 32 ml/min (range 8–84) 6 months after transplantation (P<0.001). Three patients (11%) received dialysis post-transplant of whom two underwent kidney transplantation. Immunosuppressive induction therapy with rabbit-antithymocyte-globulin compared to daclizumab resulted in fewer treatments for acute rejection within the first 3 months post-transplant (P=0.05 at 5–8 weeks). Burkholderia multivorans was present in three patients pre-transplant with satisfying long-term outcome in one patient. Conclusions: Lung transplantation is a well-established life-extending treatment for patients with CF and end-stage lung disease. The operative mortality is low and CF patients have a significant early survival benefit after lung transplantation. Satisfying long-term results can be achieved in this young and severely ill group of patients.