Department of Anaesthesiology, University Hospital, LMU Munich, Munich, Germany.
Department of Anesthesiology and Operative Intensive Care Medicine (CVK, CCM), Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Xenotransplantation. 2024 Jan-Feb;31(1):e12841. doi: 10.1111/xen.12841.
Orthotopic cardiac xenotransplantation has seen notable improvement, leading to the first compassionate use in 2022. However, it remains challenging to define the clinical application of cardiac xenotransplantation, including the back-up strategy in case of xenograft failure. In this regard, the heterotopic thoracic technique could be an alternative to the orthotopic procedure. We present hemodynamic data of heterotopic thoracic pig-to-baboon transplantation experiments, focusing on perioperative xenograft dysfunction and xenograft overgrowth.
We used 17 genetically modified piglets as donors for heterotopic thoracic xenogeneic cardiac transplantation into captive-bred baboons. In all animals, pressure probes were implanted in the graft's left ventricle and the recipient's ascending aorta and hemodynamic data (graft pressure, aortic pressure and recipient's heart rate) were recorded continuously.
Aortic pressures and heart rates of the recipients' hearts were postoperatively stable in all experiments. After reperfusion, three grafts presented with low left ventricular pressure indicating perioperative cardiac dysfunction (PCXD). These animals recovered from PCXD within 48 h under support of the recipient's heart and there was no difference in survival compared to the other 14 ones. After 48 h, graft pressure increased up to 200 mmHg in all 17 animals with two different time-patterns. This led to a progressive gradient between graft and aortic pressure. With increasing gradient, the grafts stopped contributing to cardiac output. Grafts showed a marked weight increase from implantation to explantation.
The heterotopic thoracic cardiac xenotransplantation technique is a possible method to overcome PCXD in early clinical trials and an experimental tool to get a better understanding of PCXD. The peculiar hemodynamic situation of increasing graft pressure but missing graft's output indicates outflow tract obstruction due to cardiac overgrowth. The heterotopic thoracic technique should be successful when using current strategies of immunosuppression, organ preservation and donor pigs with smaller body and organ size.
原位心脏异种移植技术取得了显著进展，导致 2022 年首次进行了同情使用。然而，定义心脏异种移植的临床应用仍然具有挑战性，包括异种移植物失败时的备份策略。在这方面，异位胸腔技术可能是原位手术的替代方法。我们介绍了异位胸腔猪-狒狒异种心脏移植实验的血液动力学数据，重点关注围手术期异种移植物功能障碍和异种移植物过度生长。
我们使用 17 只基因修饰的小猪作为供体，进行异位胸腔异种心脏移植到圈养繁殖的狒狒体内。在所有动物中，压力探针被植入移植物的左心室和受体的升主动脉，连续记录血液动力学数据（移植物压力、主动脉压力和受体心率）。
所有实验中，受体心脏的主动脉压力和心率在手术后均保持稳定。再灌注后，3 个移植物的左心室压力低，表明存在围手术期心脏功能障碍（PCXD）。这些动物在受体心脏的支持下，在 48 小时内从 PCXD 中恢复，与其他 14 只动物的存活率没有差异。48 小时后，17 只动物的所有移植物压力均升高至 200mmHg，具有两种不同的时间模式。这导致移植物和主动脉之间的压力梯度逐渐增加。随着梯度的增加，移植物停止对心输出量的贡献。从植入到取出，移植物的重量明显增加。
异位胸腔心脏异种移植技术是克服早期临床试验中 PCXD 的一种可能方法，也是更好地理解 PCXD 的实验工具。移植物压力增加而移植物输出缺失的特殊血液动力学情况表明，由于心脏过度生长导致流出道梗阻。当使用当前的免疫抑制策略、器官保存和体型较小的供体猪时，异位胸腔技术应该是成功的。
