Division of Cardiothoracic Surgery, Duke University Medical Center, Durham, NC, United States of America.
Department of Pathology, Duke University Medical Center, Durham, NC, United States of America.
PLoS One. 2024 Jun 3;19(6):e0304588. doi: 10.1371/journal.pone.0304588. eCollection 2024.
Preclinical disease models are important for the advancement of therapeutics towards human clinical trials. One of the difficult tasks of developing a well-characterized model is having a reliable modality with which to trend the progression of disease. Acute rejection is one of the most devastating complications that can occur following organ transplantation. Specifically in cardiac transplantation, approximately 12% of patients will experience at least one episode of moderate or severe acute rejection in the first year. Currently, the gold standard for monitoring rejection in the clinical setting is to perform serial endomyocardial biopsies for direct histological assessment. However, this is difficult to reproduce in a porcine model of acute rejection in cardiac transplantation where the heart is heterotopically transplanted in an abdominal position. Cardiac magnetic resonance imaging is arising as an alternative for serial screening for acute rejection in cardiac transplantation. This is an exploratory study to create and define a standardized cardiac magnetic resonance screening protocol for characterizing changes associated with the presence of acute rejection in this preclinical model of disease. Results demonstrate that increases in T1 mapping, T2 mapping, left ventricular mass, and in late gadolinium enhancement are significantly correlated with presence of acute rejection.
临床前疾病模型对于推进治疗方法向人体临床试验的发展非常重要。在开发具有良好特征的模型时,其中一项艰巨的任务是拥有一种可靠的方法来跟踪疾病的进展。急性排斥反应是器官移植后最具破坏性的并发症之一。具体在心脏移植中,约有 12%的患者在第一年至少会经历一次中度或重度急性排斥反应。目前,监测临床排斥反应的金标准是进行连续的心肌活检以进行直接的组织学评估。然而,在心脏异位移植于腹部位置的急性排斥反应的猪模型中,这很难重现。心脏磁共振成像正在成为心脏移植中急性排斥反应的连续筛查的替代方法。这是一项探索性研究,旨在为这种临床前疾病模型中与急性排斥反应存在相关的变化创建和定义标准化的心脏磁共振筛查方案。研究结果表明,T1 映射、T2 映射、左心室质量和晚期钆增强的增加与急性排斥反应的存在显著相关。