Mitchell Chace B, Simmons Joe, Vo Clementine, Bakshi Kanwarpal, Juliani Julie, Fenske Julie, Hodo Carolyn L, Cleveland David C, Cleveland John D
Division of Cardiac Surgery, Department of Surgery, Children's Hospital of Los Angeles, Los Angeles, California, USA.
Michale E. Keeling Center for Comparative Medicine, MD Anderson Cancer Center, Bastrop, Texas, USA.
Xenotransplantation. 2025 Jan-Feb;32(1):e70009. doi: 10.1111/xen.70009.
There is no standard protocol for management of organ preservation for orthotopic, life-sustaining cardiac xenotransplantation, particularly for hearts from pediatric sized donors. Standard techniques and solutions successful in human allotransplantation are not viable. We theorized that a solution commonly used in reparative cardiac surgery in human children would suffice by exploiting the advantages inherent to xenotransplantation, namely the ability to reduce organ ischemic times by co-locating the donor and recipient.
Orthotopic cardiac xenotransplantation was performed from genetically engineered pigs to size matched baboons. A dose of modified Del Nido cardioplegia initiated donor heart arrest and was followed by a second dose mixed with recipient blood prior to implant. Hemodynamics and cardiac function were tracked with a combination of invasive and non-invasive measures.
Mean ischemic time and cardiopulmonary bypass times were 54.1 ± 14.6 and 84.1 ± 14 min respectively. The ejection fraction following chest closure was preserved at >50% for all animals. This finding persisted at 48hours. Mean inotropic score at 24 h post-implant was 9.7 ± 3.
Del Nido cardioplegia solution when combined with short graft ischemic times demonstrates promising outcomes to avoid primary graft dysfunction for cardiac xenografts in a small animal model of life-sustaining orthotopic cardiac xenotransplantation. Ex vivo perfusion systems may be unnecessary for successful clinical implementation of this evolving technology.
对于原位维持生命的心脏异种移植,尤其是来自小儿尺寸供体心脏的器官保存管理,尚无标准方案。在人类同种异体移植中成功的标准技术和溶液不可行。我们推测,通过利用异种移植固有的优势,即通过将供体和受体并置来减少器官缺血时间,一种常用于人类儿童心脏修复手术的溶液就足够了。
从基因工程猪到大小匹配的狒狒进行原位心脏异种移植。一剂改良的Del Nido心脏停搏液引发供体心脏停搏,然后在植入前与受体血液混合使用第二剂。通过有创和无创测量相结合的方式跟踪血流动力学和心脏功能。
平均缺血时间和体外循环时间分别为54.1±14.6分钟和84.1±14分钟。所有动物在关胸后的射血分数均保持在>50%。这一发现持续到48小时。植入后24小时的平均肌力评分是9.7±3。
在维持生命的原位心脏异种移植的小动物模型中,Del Nido心脏停搏液与较短移植物缺血时间相结合,对于避免心脏异种移植物的原发性移植物功能障碍显示出有前景的结果。对于这项不断发展的技术的成功临床应用,体外灌注系统可能并非必要。