Monitoring pig-to-primate cardiac xenografts with live internet images of recipients and xenograft telemetric signals: Histologic and immunohistochemical correlations

Monitoring pig-to-primate cardiac xenografts with live internet images of recipients and xenograft telemetric signals: Histologic and immunohistochemical correlations
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DOI:
10.1016/s1053-2498(00)00101-7
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发表时间:
2000-06-01
影响因子:
8.9
通讯作者:
Adams, DH
Adams, DH
中科院分区:
医学1区
文献类型:
--
作者:
Chen, RH;Kadner, A;Adams, DH

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背景:在清醒和不合作的灵长类动物中,监测猪到灵长类异种心脏移植通常是困难的。我们研究了通过互联网广播(1)移植受者的连续视频图像和(2)植入装置检测到的异种移植遥测信号来监测异种移植的可能性。方法:通过苏木精-伊红染色和免疫组织化学方法检测免疫球蛋白M(IgM)和补体膜攻击复合体(MAC)的沉积情况,并对异位狒狒(n=2)和转基因猪(人补体调节蛋白CD59/DAF,n=3;MCP,n=1)进行移植。研究人员用QuickCamPro数码相机连续监测了狒狒移植受者的情况,而用国际数据科学植入式遥测系统对移植器官进行了监测。视频图像和遥测信号通过笔记本电脑通过互联网广播。结果:在移植的第14天,狒狒移植物一直保持健康,而猪的异种移植物在第5、6、7和11天被排斥。遥测记录到移植物和异种移植物有规律的节律,平均心率80-120,但异种移植物在移植物丢失前24-48小时出现心动过缓和QRS波群增宽/抑制。对受者活动的持续视频监测对于区分移植物心律失常和遥测伪影至关重要。在心脏活动停止前24小时,同种异种移植心脏活检发现少量细胞浸润,而异种移植心脏活检显示IgM和MAC沉积增加,并伴有广泛的血栓和心肌损伤。结论:联合视频监测受体活动和移植物遥测信号是持续监测大型、不合作、清醒的灵长类动物腹部心脏移植物的有效方法。与进行性心动过缓相关的QRS波群扩大与异种移植排斥反应的组织学和免疫组织化学证据相关。
Background: Monitoring pig-to-primate cardiac xenografts is often difficult in awake and uncooperative primates. We investigated the possibility of monitoring xenotransplantation through internet broadcasting of (1) continuous video images of transplant recipients and (2) xenograft telemetric signals detected by an implanted device. The telemetric readings were later compared with histology and immunohistochemistry for signs of rejection.Methods: Heterotopic baboon-to-baboon (n = 2) and transgenic pig (human complement regulatory proteins CD59/DAF, n = 3; MCP, n = 1)-to-baboon transplants were performed with serial biopsies for hematoxylin-and-eosin staining and immunohistochemical detection of immunoglobulin M (IgM) and complement membrane attack complex (MAC) deposition. Baboon recipients were continuously monitored with a QuickCamPro digital camera, whereas grafts were monitored with a Data Science International implantable telemetric system. Video images and telemetric signals were broadcast over the Internet through a laptop computer.Results: Baboon allografts remained healthy until explant on Day 14, whereas pig xenografts were rejected on Day 5, 6, 7, and 11. Telemetry of allografts and xenografts documented regular rhythm with an average heart rate of 80 to 120, but xenografts developed bradycardia and widened/dampened QRS complexes 24 to 48 hours before graft loss. Continuous video monitoring of recipient activities was vital in differentiating between graft arrhythmias and telemetric artifacts. Allograft biopsies showed little cellular infiltrate, whereas xenograft biopsies showed increasing IgM and MAC deposition, with extensive thrombi and myocardial damage 24 hours before cessation of cardiac activities.Conclusions: Combined video surveillance of recipient activities and graft telemetric signals is a useful method to continuously monitor abdominal cardiac grafts in large, uncooperative, awake primates. QRS-complex widening associated with progressive bradycardia correlated with histologic and immunohistochemical evidence of xenograft rejection.