【作者】 郑俊猛；

【导师】 陈忠华；

【作者基本信息】 华中科技大学 ， 外科学， 2010， 博士

【摘要】 目的：研究长冷缺血时间供心心脏移植的可行性和临床疗效。方法：分为两组,研究组：边缘性供心移植组,即边缘性供心(冷缺血时间>6小时)→受者；对照组：常规供心移植组,即常规供心(冷缺血时间<6小时)→受者；两组均行临床心脏移植,手术方式为双腔静脉法,并进行下述处理：(1)检测两组供心移植前后质量(病理切片、能量代谢和心肌酶谱)；(2)研究组术中或术后使用ECMO支持治疗；(3)安置心肌内心电图装置并无创监测排异反应；(4)比较两组心脏移植的近期效果、ECMO支持治疗的效果和心肌内心电图无创监测急性排斥反应的效果。结果：(1)供体一般资料的比较：入选研究组供者16例,入选对照组供者30例,两组一般情况、年龄等可能影响移植疗效和术后并发症的各项因素比较无显著性差异(P>0.05)。(2)受者一般资料比较：研究组与对照组比较,可能影响手术效果和术后并发症的一般情况各项因素比较无显著性差异(P>0.05)。(3)供心移植前质量判定：1)供心移植前心肌组织形态学检查：研究组和对照组比较：心肌组织均没有明显的形态学改变。2)能量代谢：两组供心移植前后心肌细胞能量检测(心肌细胞膜Na,K-ATP酶检测,即ATP酶失活差异)比较,在供心摘取前无统计学意义(t=0.44,P>0.05),在供心摘取后(t=11.86,P<0.05)有统计学意义。3)心肌损伤标志物(心肌酶谱)检测：供心摘取前后,研究组与对照组比较均有明显差异(P<0.05)。(4)心脏移植手术过程分析：两组受者在全身麻醉及常规体外循环或ECMO替代体外循环下施行移植手术,手术过程均顺利。研究组：主动脉阻断时间53-131 min(644-19 min)；11例使用i-ECMO方案(以ECMO替代CPB,术后延续ECMO支持治疗)；3例使用s-CPB方案(常规CPB后并行循环超过1小时后仍不能撤机,则立即转为ECMO支持治疗)。对照组：主动脉阻断时间50-125 min(60±15min)。30例全部使用常规CPB并顺利撤机,主动脉阻断时间比较：研究组与对照组(t=0.94),比较均无统计学意义(P>0.05)。(5)心脏移植术后近期结果：研究组：共完成心脏移植16例,其中近期(术后30天内)死亡2例。对照组：共完成心脏移植30例,其中近期(术后30天内)死亡2例。两组成功率比较差异比较无统计学意义(P>0.05)。(6)ECMO支持治疗效果分析：研究组使用ECMO情况：①使用i-ECMO方案：术中以ECMO替代CPB并术后延续ECMO支持者11例；②使用s-CPB方案：术术中不能撤离常规CPB而立即使用ECMO支持治疗者3例。使用ECMO支持治疗时间48-450hs(140±15hs)。使用iECMO方案11例中10例成功撤机,1例因术后当天吻合口大出血死亡。使用sCPB方案3例中2例成功撤机,1例不能撤机,因多器官衰竭死亡。总撤机率85.71%(12／14)。发生ECMO的并发症包括：血栓形成1例、肝肾功能衰竭2例、神经系统并发症1例、出血和渗血2例、氧合器置换8例。多数病人的并发症均经相应处理好转或治愈。(7)心肌内心电图：术后两组受者行心肌内心电图(IMEG)723份：心肌内心电图监测排斥反应阳性预见率63.62%(14／22),阴性预见率99.71%(699／701)。结论：(1)供心质量可以在移植前被检测,尤其以组织能量代谢和心肌酶谱指标为敏感。(2)两组移植结果差异无明显统计学意义。(3)边缘性供心(冷缺血时间过长)经ECMO支持治疗后,移植结果良好。(4)心肌内心电图可预见移植心排斥反应。(5)边缘性供心(长冷缺血时间供心)在有效措施处理下是可以使用的,应用的关键是对边缘性供心的评价-“复苏”-再评价。(6)边缘性供心心脏移植围手术期应积极应用ECMO支持治疗,推荐使用i-ECMO方案。目的：研究应用需大剂量药物维护的供体心脏之心脏移植的可行性及临床疗效。方法：首都医科大学附属安贞医院与中山大学附属中山医院双中心合作共同完成心脏移植3例,所有3例供心在获取前均需大剂量多巴胺维护。需大剂量多巴胺维护的供体心脏属于“边缘性供心”的范畴,血流动力学稳定,电解质酸碱平衡良好,没有明显心源性肺水肿。结果：3例过程顺利,病人术后均无需机械辅助治疗,无需连续性肾脏替代治疗,均顺利痊愈出院,生活质量良好。结论：应用需大剂量多巴胺维护的供体心脏的心脏移植能取得良好的近期结果,做好供体维护,供心的心肌保护(缩短冷缺血时间)、供体与受体匹配等方面是成功的关键。目的探讨连续性血液净化治疗(CBP,continuous blood purification)在心脏移植中的作用,总结包括应用CBP为心脏移植受体行术前准备及为心脏移植受体术后并发重症急性肾功能衰竭(ARF, acute renal failure)治疗的经验。方法自2004.6-2009.12中山大学附属中山医院共完成的22例同种异体原位心脏移植及1例心肾联合移植,1例接受心脏移植的受体应用CBP行术前准备,CBP模式为连续性静脉-静脉血液滤过(CVVH, Continuous Veno-Venous Hemofiltration),奏效明显。该受体术前诊断：限制型心肌病,心功能为Ⅳ级(NYHA)。病人反复心力衰竭并渐进性发展,出现轻度肾前性急性肾功能衰竭(ARF)。CBP治疗3天,治疗持续时间12小时／天,超滤2000-2200ml/天,25天后该受体接受心脏移植术。另外,同一时期内,3例接受心脏移植的受体术后并发ARF。其中2005年以前共10例中有2例分别在术后第2,3天发生ARF,CBP治疗3天和6天。2005年以后13例中1例术后当天发生严重ARF,CBP治疗19天,无效死亡。结果以CBP行心脏移植术前准备的受体治疗后恶心、呕吐、腹胀等症状明显缓解,恢复正常尿量,双肺湿罗音、腹水征消失；生化参数转正常；血压平稳,血管活性药物用量明显减少。接受心脏移植术后前5天尿量保持在2800ml/d以上,未出现严重右心衰及感染,ICU停留时间6天。心脏移植术后并发严重ARF的受体共3例,其中2例病人治愈顺利出院,肾功能良好,恢复正常工作。结论心脏移植术前并发的ARF多为肾前性肾功能衰竭,往往都是可逆的,尽早应用CBP是一种积极有效的措施。可使用CBP作为心脏移植的术前准备措施,合并ARF程度并非一定是重度。心脏移植受体术后发生严重ARF与术前心功能、术中平均动脉压、术后心功能以及使用免疫抑制剂等肾毒性药物等因素有关,及时找出原因,对症治疗；应积极使用CBP,能提高心脏移植成功率。更多还原

【Abstract】 Objective To explore the probability of heart transplantation with prolonged cold ischemic time cardiac grafts and its outcomes in two centers.Methods According to the kind of grafts, two experimental groups were established:marginal donor group (patients received the donor heart with cold ischemic time more than 6-hours) and control group (patients received the donor heart with cold ischemic time less than 6-hours), then:(1)Quality of grafts were detected by pathological section, energy metabolism and the cardiac muscle zymogram between marginal donor group and control group. (2) ECMO were used to support circulation for cases in marginal donor group. (3) In-muscle-electrocardiogram (IMEG) tests were performed in recipients. (4)The terms of outcomes of heart transplantation, ECMO and IMEG were analyzed.Results (1) Outcomes between marginal donor group and control group:there was no significant difference (P>0.05) of achievement ratio in heart transplantation (13/15 vs 28/30) in 30 days after transplantation. (2) Data for quality of grafts were successfully got in marginal donor group and control group. (3) In marginal donor group,11 cases were support by intraoperative ECMO (i-ECMO) and 2 cases after standart cardiopulmonary bypass (s-CPB). As consequence, only 2 cases in this group died. (4) IMEG were performed in recipients with 22 cases positive prediction (14 rejections were confirmed) and 699 cases negative prediction (701 rejections were confirmed). Conclusion (1) There was no significant difference of outcomes between patients who receive the donor hearts with cold ischemic time more than 6-hours and patients who receive the donor hearts with cold ischemic time less than 6-hours. (2) Quality of grafts could predict outcomes of transplantation. (3) intraoperative ECMO (i-ECMO group) or ECMO support after Standard cardiopulmonary bypass (s-CPB group) could support the circulation well for marginal donor recipients. (4) To some extent, IMEG could predicted cardiac rejections.Objective To report the short term results and summarize the experience of heart transplantation with cardiac grafts from donors with high dose dopermin maintenancedMethods From September 2009 to April 2010,3 cases of heart transplantation with Cardiac grafts from donors with high dose Dopermin maintenanced were performed in two centers. Before donor hearts were harvested, donors were maintained to be a good homodynamic stability and, satisfying acid base status, electrolysis and stable haemodynamics without pulmonary edema by high dose dopamine.Results The processes of heart transplantation were successful in 3 cases and the recipients were survived with good life quality.Conclusion Heart transplantation with cardiac grafts from donors after high dose dopamine maintenanced could have good outcomes. Objective To discuss the effectiveness of CBP (continuous blood purification) in heart transplantation. Summarize the experience in perioperative usage.Methods A recipient who was waiting for heart transplantation, with restrictive cardiomyopathy, heart function NYHAⅣ, appeared obstinate heart failure and perennial inadequacy, improved heart function by CBP with the mode of CVVH (Continuous Veno-Venous Hemofiltration). The recipient was treated for 3 days,12 hours per day, the dose of ultrafiltrated is 2000-2200ml/d,25 days later, the recipien undertook heart transplant.22 cases of Orthotopic Heart transplantation and 1 case of heart-kidney transplantation in 2004.6-2009.12 in Zhongshan People’s Hospital.2 recipients in 10 before the year of 2005 with ARF in 2-3 days after operation and were treated by CBP for 3,6 days. One recipience in 13 after the year of 2005 with ARF in 0 day after operation and was trented by CBP for 19 days.Results After the treatment of CBP, the recipient was relieved from nausea, vomit and abdominal distention. Urinary production was recovered. The sign of bubble and ascites was disappeared. The biochemistry analysis was normal. The vital sign was stable. The dose of vasoactive agent was decreased obviously. After the heart transplantation, the urinary production maintain 2800ml/d in the first 5 days. The recipient returned to isolation ward on 6th day, without serious right heart failure and infection. One recipience died. The other 2 recipiences who were cured, were provide well renal functions and came back to work.Conclusion The renal insufficiency before heart transplantation is prerenal insufficiency usually. It is reversible, so we should adopt active measure just as CBP. CBP is used for the preparation of heart transplantation, by no means serious renal insufficiency. The reasons of ARF after Heart transplantation are about heart function before operation, the mean blood pressure during operation, heart function and make use of renal-toxic drug. Have effect process can improve the survival rate after Heart transplantation.更多还原