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在生长中的绵羊模型中,脱细胞主动脉同种异体移植物与肺动脉自体移植物用于主动脉瓣置换:植入后20个月的血流动力学和形态学结果

Decellularized aortic allografts versus pulmonary autografts for aortic valve replacement in the growing sheep model: haemodynamic and morphological results at 20 months after implantation.

作者信息

Tudorache Igor, Theodoridis Karolina, Baraki Hassina, Sarikouch Samir, Bara Christoph, Meyer Tanja, Höffler Klaus, Hartung Dagmar, Hilfiker Andres, Haverich Axel, Cebotari Serghei

机构信息

Department of Cardiac-, Thoracic-, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Hannover, Germany

Department of Cardiac-, Thoracic-, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Hannover, Germany.

出版信息

Eur J Cardiothorac Surg. 2016 Apr;49(4):1228-38. doi: 10.1093/ejcts/ezv362. Epub 2015 Oct 24.

Abstract

OBJECTIVES

Pulmonary autografts (PAs) represent the substitute of choice for aortic valve (AV) replacement, especially in children and young adults. Similarly, decellularized aortic valve allografts (DAVAs) have shown excellent mid-term function when implanted in the systemic circulation. The aim of this study was to compare the performance of DAVAs with that of pulmonary autografts after a Ross procedure in the growing sheep model.

METHODS

AV root replacement was performed in female lambs (25 ± 3.4 kg) using either DAVAs (n = 5) or pulmonary autografts (n = 5) as in the Ross procedure. Sheep undergoing the Ross procedure received a decellularized pulmonary allograft in place of pulmonary valve. Haemodynamics was investigated by echocardiography and magnetic resonance imaging. The roots were explanted at 20 months and examined by histology to determine the degree of repopulation and quality of the extracellular matrix, and by immunohistochemistry to characterize the repopulating cells.

RESULTS

The mean valve diameter increased from 16 to 21 and from 16 to 25 mm in DAVAs and PAs, respectively. At explantation, one PA and one DAVA exhibited moderate insufficiency. Significant differences in transvalvular gradient were only found in PAs between implantation and prior to explantation. The cusps of all implants were soft, pliable and showed no major signs of degeneration. In the decellularized allografts, cell repopulation occurred at the wall and cusp level with a well-maintained, three-layered cusp structure. Ventricular cusp surface of decellularized allografts was more strongly repopulated than the arterial surface. Cusps were covered with cells positive for endothelial markers and were also repopulated by interstitial cells.

CONCLUSIONS

DAVAs and PAs provide adequate haemodynamics after AV replacement in the growing sheep. While decellularized grafts are repopulated by endothelial and interstitial cells, autografts maintain in general their native cell distribution. Maintenance of valvular competence during enlargement of the valve ring is, in our opinion, representative of the capacity for physiological growth in both graft types.

摘要

目的

肺动脉自体移植物(PAs)是主动脉瓣(AV)置换的首选替代物,尤其适用于儿童和年轻成人。同样,脱细胞主动脉瓣同种异体移植物(DAVAs)在植入体循环后已显示出优异的中期功能。本研究的目的是在生长中的绵羊模型中比较DAVAs与肺动脉自体移植物在Ross手术后的性能。

方法

对雌性羔羊(25±3.4 kg)进行AV根部置换,采用DAVAs(n = 5)或肺动脉自体移植物(n = 5),如同Ross手术。接受Ross手术的绵羊接受脱细胞肺同种异体移植物替代肺动脉瓣。通过超声心动图和磁共振成像研究血流动力学。在20个月时取出根部,通过组织学检查确定再细胞化程度和细胞外基质质量,并通过免疫组织化学对再细胞化细胞进行表征。

结果

DAVAs和PAs的平均瓣膜直径分别从16 mm增加到21 mm和从16 mm增加到25 mm。在取出时,一个PA和一个DAVA表现出中度关闭不全。仅在PAs中发现植入时和取出前跨瓣膜梯度有显著差异。所有植入物的瓣叶柔软、柔韧,未显示出主要的退变迹象。在脱细胞同种异体移植物中,细胞在壁和瓣叶水平发生再细胞化,瓣叶结构保持良好的三层结构。脱细胞同种异体移植物的心室瓣叶表面比动脉表面的再细胞化更强。瓣叶覆盖有内皮标记物阳性的细胞,也有间质细胞再细胞化。

结论

DAVAs和PAs在生长中的绵羊进行AV置换后提供了足够的血流动力学。虽然脱细胞移植物由内皮细胞和间质细胞再细胞化,但自体移植物总体上保持其天然细胞分布。我们认为,在瓣膜环扩大期间维持瓣膜功能代表了两种移植物类型的生理生长能力。

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