ELECTROPHYSIOLOGIC MONITORING OF ALLOGRAFT REJECTION

同种异体移植排斥反应的电生理监测

• 批准号: 3473469
• 负责人: T B FERGUSON
• 金额: $ 6.32万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-05-01 至 1996-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3473469
• 关键词: biomaterial compatibility; biopsy; denervation; dogs; electrocardiographic monitor; electrophysiology; heart circulation; heart function; heart transplantation; human subject; laboratory rat; method development; xenotransplantation

The grant proposal presented here describes the development and experimental and clinical validation of a noninvasive method to reliably screen for and detect cardiac allograft rejection. A previously examined electrophysiologic parameter, the first fast negative deflection in the unipolar electrogram, termed UPPA, has been monitored following heterotopic canine transplantation, with a sensitivity and specificity for detecting rejection that is equivalent to standard endomyocardial biopsy techniques. However, these UPPA data can be obtained noninvasively using pacemaker telemetric technology by transcutaneously interrogating implanted pacemakers connected to epicardial pacemaker leads implanted on the allograft. In a series of laboratory experiments, this project will determine the principal factors that lead to changes in UPPA under both normal and abnormal conditions; will establish quantitative thresholds for the early detection of rejection with UPPA as compared with histologic evidence of rejection; will correlate these changes in UPPA during rejection with alterations in regional myocardial blood flow; will examine the effect of other electrophysiologic, mechanical and environmental factors on UPPA in normal hearts, in denervated hearts and in allografts undergoing early rejection; and will determine the optimal parameters for non-invasive telemetric monitoring, storage, analysis, and retrieval of UPPA data. Finally, the project will demonstrate the validity and cost- effectiveness of the UPPA monitoring system, both in-hospital and at home, in human cardiac allograft recipients. Such a system would decrease the cost and morbidity of screening endomyocardial biopsies, and may allow for closer surveillance and earlier diagnosis of rejection, with subsequent prolongation of allograft survival.

这里提出的赠款提案描述了发展和 无创方法的实验和临床验证 筛选并检测心脏同种异体移植排斥。 先前检查的 电生理参数，第一个快速偏转 单极电图，称为UPPA，已在异位后进行了监测 犬类移植，具有检测的灵敏度和特异性 等效于标准内膜活检技术的排斥反应。 但是，这些UPPA数据可以使用起搏器无创获得 远程征服技术通过植入植入 与心外膜起搏器有关的起搏器植入了 同种异体移植。 在一系列实验室实验中，该项目将 确定导致UPPA两者变化的主要因素 正常和异常条件；将建立定量阈值 与组织学相比，早期检测到UPPA排斥反应 拒绝的证据；将在UPPA中相关联 区域心肌血流的改变；会检查 其他电生理，机械和环境的影响 在正常心脏中的UPPA上的因素，死心和同种异体移植中 受到早期拒绝；并将确定 非侵入性远程监测，存储，分析和检索 UPPA数据。 最后，该项目将证明有效性和成本 - UPPA监测系统的有效性，无论是院内还是在家中， 在人类心脏同种异体移植受体中。 这样的系统会降低 筛查内膜活检的成本和发病率，可能允许 近距离监视和更早的拒绝诊断，随后 同种异体移植生存的延长。