Labarrere C A, Nelson D R, Faulk W P
Center for Reproduction and Transplantation Immunology, Methodist Research Institute, Indianapolis, IN 46202, USA.
JAMA. 1997 Oct 8;278(14):1169-75.
The development of coronary artery disease in heart transplants is often associated with graft failure. Early detection of allografts prone to develop this disease is essential to institute new therapeutic approaches that could prolong allograft function.
To determine if early activation of arterial/arteriolar endothelium predicts the development of coronary artery disease, graft failure, or both in transplanted human hearts.
Prospective cohort study.
Heart Transplant Center.
A total of 121 consecutive adult cardiac allograft recipients who received transplants between 1988 and 1995 and were followed up through 1996.
Development of coronary artery disease and graft failure.
Immunocytochemistry was performed on serial endomyocardial biopsy specimens to evaluate endothelial activation markers (intercellular adhesion molecule-1 and histocompatibility antigen HLA-DR) in arteries and arterioles. The presence and progression of coronary artery disease was evaluated by annual coronary angiograms with side-by-side comparisons.
None of the 121 donor hearts showed arterial/arteriolar endothelial activation before transplantation. Arterial/arteriolar endothelial activation was present in 78 and absent in 43 of 121 allografts during the first 3 months after transplantation. The time of appearance and the proportion of biopsy specimens showing endothelial activation during these first 3 months were significantly associated with the risk of developing coronary artery disease, the progression of the disease, and the time required to develop the disease (P<.001). Significantly more patients with arterial/arteriolar endothelial activation died or received a second transplant (P<.001).
Activation of arterial/arteriolar endothelium in transplanted human hearts predicts development of coronary artery disease and increased risk of graft failure.
心脏移植中冠状动脉疾病的发展常与移植物功能衰竭相关。早期检测易患此病的同种异体移植物对于采用可延长移植物功能的新治疗方法至关重要。
确定动脉/小动脉内皮的早期激活是否可预测移植的人心冠状动脉疾病、移植物功能衰竭或两者的发生。
前瞻性队列研究。
心脏移植中心。
共有121例连续的成年心脏同种异体移植受者，他们于1988年至1995年接受移植，并随访至1996年。
冠状动脉疾病和移植物功能衰竭的发生情况。
对系列心内膜心肌活检标本进行免疫细胞化学检测，以评估动脉和小动脉中的内皮激活标志物（细胞间黏附分子-1和组织相容性抗原HLA-DR）。通过每年的冠状动脉造影并排比较来评估冠状动脉疾病的存在和进展情况。
121例供体心脏在移植前均未显示动脉/小动脉内皮激活。121例同种异体移植物中，78例在移植后的前3个月出现动脉/小动脉内皮激活，43例未出现。在这最初的3个月内，内皮激活出现的时间以及显示内皮激活的活检标本比例与发生冠状动脉疾病的风险、疾病进展以及发生疾病所需的时间显著相关（P<0.001）。动脉/小动脉内皮激活的患者死亡或接受二次移植的比例明显更高（P<0.001）。
移植的人心动脉/小动脉内皮激活可预测冠状动脉疾病的发生以及移植物功能衰竭风险的增加。
