Labarre C A, Nelson D R, Pitts D E, Kirlin P C, Halbrook H
Methodist Research Institute, Clarian Health, Indianapolis, IN, USA.
Am J Transplant. 2001 Sep;1(3):251-9. doi: 10.1046/j.1600-6135.ajt10309.x.
Transplant coronary artery disease is the leading cause of long-term morbidity and mortality in cardiac transplantation. We developed a model for early identification of patients who subsequently develop coronary artery disease and graft failure. Serial biopsies obtained from 141 cardiac allografts (5.5 +/- 0.1 biopsies/patient) during the first 3 months post-transplant were evaluated immunohistochemically for deposition of myocardial fibrin, depletion of arteriolar tissue plasminogen activator, presence of arterial/arteriolar endothelial activation markers, and changes in vascular antithrombin. An immunohistochemical risk score was developed with a minimum value of 0 (normal) and a maximum value of 4 (most abnormal). Scores of 0 (low risk), 0.5-3.0 (moderate risk), and 3.5-4.0 (high risk) were analyzed for association with graft failure and development, severity, and progression of coronary artery disease detected using serial coronary angiograms (3.9 +/- 0.2/patient). Allografts with high immunohistochemical risk scores in the first 3months post-transplant developed more coronary artery disease (p<0.001), developed coronary artery disease earlier (p<0.001), developed more severe disease (p<0.001), and showed more disease progression (p<0.001) than allografts with moderate or low scores. Allografts with high immunohistochemical risk scores in the first 3 months post-transplant failed more (p<0.001) and failed earlier (p<0.001) than allografts with moderate or low scores. The present study demonstrates that early changes in the microvasculature are associated with impending coronary artery disease and graft failure in cardiac allograft recipients and suggests that treatment needs to be instituted early after transplantation in order to improve outcome.
移植后冠状动脉疾病是心脏移植中长期发病和死亡的主要原因。我们开发了一种模型，用于早期识别随后发生冠状动脉疾病和移植物衰竭的患者。对141例心脏同种异体移植受者在移植后前3个月内获取的系列活检组织（每位患者5.5±0.1次活检）进行免疫组织化学评估，检测心肌纤维蛋白沉积、小动脉组织型纤溶酶原激活物耗竭、动脉/小动脉内皮激活标志物的存在以及血管抗凝血酶的变化。制定了一个免疫组织化学风险评分，最小值为0（正常），最大值为4（最异常）。分析了0分（低风险）、0.5 - 3.0分（中度风险）和3.5 - 4.0分（高风险）与移植物衰竭以及使用系列冠状动脉造影（每位患者3.9±0.2次）检测到的冠状动脉疾病的发生、严重程度和进展之间的关联。移植后前3个月免疫组织化学风险评分高的同种异体移植物比中度或低评分的移植物发生更多的冠状动脉疾病（p<0.001）、更早发生冠状动脉疾病（p<0.001）、疾病更严重（p<0.001）且疾病进展更多（p<0.001）。移植后前3个月免疫组织化学风险评分高的同种异体移植物比中度或低评分的移植物失败更多（p<0.001）且更早失败（p<0.001）。本研究表明，微血管的早期变化与心脏同种异体移植受者即将发生的冠状动脉疾病和移植物衰竭相关，并提示需要在移植后早期开始治疗以改善结局。
