11C-N-CH3-Dopamine神经显像对心肌"缺血记忆"的实验研究

Myocardial ischemia can lead to reduced myocardial perfusion, abnormal metabolism of fatty acid and glucose as well as malfunction of cardiac nerve system. Myocardial perfusion can be normal shortly after coronary blood supply restoration , but the change of metabolic and nervous function persists for longer. The prolonged change in metabolism and nervous function remarks occurring of ischemia, therefore, it is termed ischemic memory. Ischemic memory is of importance in patients with symptom relief or disappearing after brief ischemia, especially with acute coronary syndrome without elevated ST-segment elevation and increased cardiac enzyme. It is very high risky for patients without assessment of ischemia. Routine clinical examinations, such as ECG, cardiac enzyme, ultrasound and imaging of myocardial perfusion, are difficult to figure out the past ischemia, leading to misdiagnosis. Routine metabolic imaging methods with fatty acid or glucose can detect ischemic memory with short window time (less than 24 hours). Therefore, new imaging methods with high efficient are required to investigate the probability, severity, duration, reversibility in detection of ischemic memory. The current study is designed to investigate whether novel cardiac nervous imaging agent, 11C-N-NH3-Dopamine developed by us, can provide longer window and more sensitivity for ischemic memory by comparison with glucose and fatty acid metabolism.

心肌缺血可引起心肌灌注减低、脂肪酸和葡萄糖代谢异常及神经功能异常等。心肌血流灌注短时间内可恢复正常，而代谢和神经功能异常却可持续较长时间，是心肌曾经发生缺血的标志，被称为心肌的"缺血记忆"。"缺血记忆"的识别对于就诊时症状已有所改善或消失的急性胸痛患者，特别心电图和心肌酶学正常的急性冠脉综合征患者很有意义。其发生心血管事件几率很高。常规心电图、酶学、普通超声和常规心肌血流灌注显像方法很难判断曾经发生过的缺血，易导致漏诊，而诊断灵敏度较高的的脂肪酸、葡萄糖代谢显像方法诊断缺血记忆的时间窗较短（24小时）,寻找更加高效的方法去回忆先前的缺血对于不同的缺血事件引起的"缺血记忆"发生的概率、程度、持续时间、可逆性非常重要，本研究采用自主研发的神经显像剂11C-N-NH3-Dopamine对心肌"缺血记忆"进行研究并与糖代谢及脂代谢显像对比，可能对心肌"缺血记忆"提供更长的时间窗和更高的灵敏度。

本项目利用心肌代谢18F-FDG显像与心肌血流灌注[13N]-ammonia显像进行对比研究并评价心肌缺血时心脏代谢功能的敏感性。缺血研究采用12只巴马小型猪形成心肌缺血模型，分为8分钟组、15分钟组和假手术组，每组4只。在造模前、造模成功后24小时、48小时、72小时及1周后分别进行 [13N]-ammonia显像和18F-FDG代谢显像进行对比分析。结果为（1）相同时间段显像结果为：缺血模型心肌代谢18F-FDG的缺损体积>心肌血流灌注[13N]-ammonia的缺损体积。（2）随着缺血时间的延长，缺血程度加重，心肌缺血区域增大。结论（1）18F-FDG代谢显像与[13N]-ammonia静息心肌血流灌注显像相比，缺血状态下心脏代谢的损伤远比灌注损伤范围大且程度重，因而18F-FDG代谢显像诊断心肌缺血更灵敏。（2）心肌缺血后，轻中度缺血组与重度缺血组相比，18F-FDG代谢显像重度心肌缺血组心肌的缺血区域较轻中度大。（3）心肌代谢的缺损区在缺血后的24小时最大，随着时间的延长缺血范围逐渐减小-消失。