Early Experience With Preclinical Perioperative Cardiac Xenograft Dysfunction in a Single Program.
Early Experience With Preclinical Perioperative Cardiac Xenograft Dysfunction in a Single Program.
复制标题
DOI：
10.1016/j.athoracsur.2019.08.090
复制
发表时间：
2020-05
期刊：
影响因子：
--
通讯作者：
Mohiuddin MM
中科院分区：
文献类型：
--
作者：
DiChiacchio L;Singh AK;Lewis B;Zhang T;Hardy N;Pasrija C;Morales D;Odonkor P;Strauss E;Williams B;Deatrick KB;Kaczorowski DJ;Ayares D;Griffith BP;Bartlett ST;Mohiuddin MM
McGregor等人认为围手术期异种心脏移植功能障碍（PCXD）是异位异种心脏移植进入原位位置的主要障碍。其特点是在移植后24-48小时内无排斥反应的情况下移植物功能障碍。我们描述了我们在单个程序中使用PCXD的经验。对6只健康狒狒进行了基因工程猪心脏原位移植。免疫抑制方案包括抗cd20单抗、胸腺球蛋白、眼镜蛇毒因子和抗cd40单抗诱导，并使用抗cd40单抗、MMF和逐渐减少剂量的类固醇维持。采用遥测技术评估接枝功能。体外膜氧合用于支持一名受者。一个完整的人类临床移植团队参与了这些实验，并由熟练的移植外科医生进行了手术。在这些实验中，最大存活时间为40小时。手术过程顺利，所有心脏均顺利脱离体外循环（CPB）。CPB分离后，通常需要使用抗肌力药物和血管加压药物。异种心脏移植物立即表现良好，但在最初的几个小时内需要增加支持，尽管进行了最大的干预，但最终还是出现了骤停。所有心脏立即移植；组织学未见排斥反应。尽管有出色的手术技术、平稳的CPB脱机和足够的初始功能，原位异种心脏移植在24-48小时内缓慢失败，没有排斥反应的证据。改进保存技术和减少供器官缺血时间可能能够改善PCXD。
Peri-operative cardiac xenograft dysfunction (PCXD) was described by McGregor et al. to be a major barrier to the translation of heterotopic cardiac xenotransplantaton into the orthotopic position. It is characterized by graft dysfunction in the absence of rejection within 24-48 hours of transplantation. We describe our experience with PCXD at a single program. Orthotopic transplantation of genetically engineered pig hearts was performed in 6 healthy baboons. The immunosuppression regimen included induction by anti-CD20 mAb, Thymoglobulin, cobra venom factor and anti-CD40 mAb and maintenance with anti-CD40 mAb, MMF and tapering doses of steroids. Telemetry was used to asses graft function. Extracorporeal membrane oxygenation was used to support one recipient. A full human clinical transplant team was involved in these experiments and the procedure was performed by skilled transplant surgeons. A maximal survival of 40 hours was achieved in these experiments. The surgical procedures were uneventful and all hearts were weaned from cardiopulmonary bypass (CPB) without issue. Support with inotropes and vasopressors was generally required after separation from CPB. The cardiac xenografts performed well immediately, but within the first several hours required increasing support and ultimately suffered arrest despite maximal interventions. All hearts were explanted immediately; histology showed no signs of rejection. Despite excellent surgical technique, uneventful weaning from CPB, and adequate initial function, orthotopic cardiac xenografts slowly fail within 24-48 hours without evidence of rejection. Modification of preservation techniques and minimizing donor organ ischemic time may be able to ameliorate PCXD.
登录
查看更多内容
DOI：
10.1111/j.1600-6143.2011.03846.x
发表时间：
2012-03
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Mohiuddin MM;Corcoran PC;Singh AK;Azimzadeh A;Hoyt RF Jr;Thomas ML;Eckhaus MA;Seavey C;Ayares D;Pierson RN 3rd;Horvath KA
通讯作者：
Horvath KA
影响因子：
0.9
作者：
Horvath, K. A.;Corcoran, P. C.;Singh, A. K.;Hoyt, R. F.;Carrier, C.;Thomas, M. L., III;Mohiuddin, M. M.
通讯作者：
Mohiuddin, M. M.
影响因子：
3.9
作者：
Singh, Avneesh K.;Chan, Joshua L.;Mohiuddin, Muhammad M.
通讯作者：
Mohiuddin, Muhammad M.
影响因子：
3.9
作者：
Byrne, Guerard W.;Du, Zeji;McGregor, Christopher G. A.
通讯作者：
McGregor, Christopher G. A.
影响因子：
1.1
作者：
Laengin, Matthias;Panelli, Alessandro;Abicht, Jan-Michael
通讯作者：
Abicht, Jan-Michael