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[心脏移植——当今的技术现状]

[Heart transplantation--state of the art today].

作者信息

Meiser B M, von Scheidt W, Weis M, Böhm D, Kur F, Koglin J, Reichenspurner H, Uberfuhr P, Reichart B

机构信息

Herzchirurgische Klinik, Klinikum Grosshadern der Ludwig-Maximilians-Universität München.

出版信息

Herz. 1997 Oct;22(5):237-52. doi: 10.1007/BF03044252.

Abstract

In spite of pharmacological progress, end stage congestive heart failure is still associated with a decrease in quality and expectation of life. Heart transplantation remains the last therapeutic option for these patients. While the one year survival rate has increased over the last few years up to 84%, a major problem remains the significant lack of donors. Therefore, the criteria for the selection of candidates for cardiac transplantation have to be kept quite tight: Evidence of poor outcome without transplantation is associated with ejection fractions below 20 to 25%, cardiac indices less than 2.01/min/m2, left ventricular filling pressure above 20 mm Hg and a enddiastolic diameter of > 80 mm. There are, however, also quite important functional parameters indicating the need for heart transplantation, e.g. the maximal oxygene uptake being less than 10 ml/kg/min or below 50% of the age-appropriate value. Elevated pulmonary vascular resistance above 4 to 5 Wood units without a significant decrease during application of prostaglandin derivatives or inhalation of NO represents a contraindication for orthotopic heart transplantation; alternatively, a heterotopic transplantation can be considered. Since there is a significant shortage of suitable donor organs, the donor criteria have been broadened, e. g. the accepted donor age was increased to 60 years. Based on these extended criteria, a careful donor evaluation including cardiac history, cardiac examination, ECG and echocardiogram has to be performed. Coronary angiography in older donors is suggested, but in many cases not possible due to circumstances. Further precondition for a good graft function is a sophisticated donor management until the time of explantation. Hypovolemia and hypocalemia, hypothermia, hypoxia and rapid lost of circulating triiodothyronine (T3) have to be detected and balanced. The cardioplegic solution used might not only have an impact on the immediate postoperative performance of the graft, but also on the long term outcome, particularly with regard to graft vessel disease. There are generally two types of solutions: Those with intracellular and those with extracellular electrolyte concentrations. In addition, the potassium concentration might be of some importance. Potassium seems to damage endothelial cells and trigger subsequent immunological reactions. Therefore, high potassium concentrations in the cardioplegic solution might correlate with the incidence of graft vessel disease during the long term follow-up. The surgical technique for orthotopic heart transplantation developed at the beginning of the sixties by Lower and Shumway has been used unchanged for the last 30 years. The only alteration recently introduced is the separate direct anastomosis of the pulmonary and systemic veins in order to improve the atrial function. Until recently the commonly employed immunosuppressive strategy after heart transplantation consisted of the standard drugs cyclosporin, azathioprin and prednisolon. Some transplant-units use additionally induction therapy with antibody preparations. Many centers, however, abolished this regimen due to significant short and long term side effects. Promising new, more specific antibodies (which are chimerized or humanised) could revive the induction concept. The most thoroughly tested novel immunosuppressive agent is tacrolimus (FK506). It has been demonstrated to be 10 to 100 times more potent than cyclosporin A in in vitro and in vivo models. It binds to a different binding protein (FK-binding-protein) than cyclosporin (cyclophilin), but has a similar mechanism of action inhibiting the expression of T-cell-activator genes for certain cytokines. First non-randomised studies after heart transplantation performed at the University of Pittsburgh revealed that significantly more tacrolimus than cyclosporin patients were free of rejection. In order to confirm these observations, we performed a prospective randomised controlled clin

摘要

尽管在药理学方面取得了进展,但终末期充血性心力衰竭仍然与生活质量下降和预期寿命缩短相关。心脏移植仍然是这些患者的最后治疗选择。虽然在过去几年中,一年生存率已提高到84%,但一个主要问题仍然是供体严重短缺。因此,心脏移植候选者的选择标准必须保持相当严格:没有移植时预后不良的证据与射血分数低于20%至25%、心脏指数小于2.0升/分钟/平方米、左心室充盈压高于20毫米汞柱以及舒张末期直径大于80毫米相关。然而,也有一些非常重要的功能参数表明需要进行心脏移植,例如最大摄氧量小于10毫升/千克/分钟或低于相应年龄值的50%。在应用前列腺素衍生物或吸入一氧化氮期间,肺血管阻力升高超过4至5伍德单位且无明显下降,这是原位心脏移植的禁忌症;或者,可以考虑进行异位移植。由于合适的供体器官严重短缺,供体标准已经放宽,例如可接受的供体年龄已提高到60岁。基于这些扩展标准,必须对供体进行仔细评估,包括心脏病史、心脏检查、心电图和超声心动图。建议对老年供体进行冠状动脉造影,但在许多情况下由于情况不允许无法进行。良好移植物功能的另一个前提条件是在取出移植物之前进行完善的供体管理。必须检测并平衡低血容量、低钙血症、体温过低、缺氧以及循环三碘甲状腺原氨酸(T3)的快速丧失。所使用的心脏停搏液不仅可能影响移植物术后的即时表现,还可能影响长期结果,特别是在移植物血管疾病方面。通常有两种类型的溶液:细胞内电解质浓度的溶液和细胞外电解质浓度的溶液。此外,钾浓度可能也很重要。钾似乎会损害内皮细胞并引发后续免疫反应。因此,心脏停搏液中高钾浓度可能与长期随访期间移植物血管疾病的发生率相关。由洛厄尔和舒姆韦在60年代初开发的原位心脏移植手术技术在过去30年中一直未变。最近引入的唯一改变是肺静脉和体静脉的单独直接吻合,以改善心房功能。直到最近,心脏移植后常用的免疫抑制策略包括标准药物环孢素、硫唑嘌呤和泼尼松龙。一些移植单位还额外使用抗体制剂进行诱导治疗。然而,许多中心由于严重的短期和长期副作用而废除了这种方案。有前景的新型、更具特异性的抗体(已进行人源化或嵌合改造)可能会使诱导概念重新流行起来。经过最全面测试的新型免疫抑制剂是他克莫司(FK506)。在体外和体内模型中,它已被证明比环孢素A的效力强10至100倍。它与环孢素(亲环蛋白)结合的不同结合蛋白(FK结合蛋白)结合,但具有类似的作用机制,抑制某些细胞因子的T细胞激活基因的表达。匹兹堡大学进行的心脏移植后首批非随机研究表明,使用他克莫司的患者比使用环孢素的患者明显更少发生排斥反应。为了证实这些观察结果,我们进行了一项前瞻性随机对照临床……

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