Johnstone M T, Botnar R M, Perez A S, Stewart R, Quist W C, Hamilton J A, Manning W J
Department of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston University School of Medicine, Boston, Massachusetts, USA.
Arterioscler Thromb Vasc Biol. 2001 Sep;21(9):1556-60. doi: 10.1161/hq0901.094242.
The process of atherosclerotic plaque disruption has been difficult to monitor because of the lack of an animal model and the limited ability to directly visualize the plaque and overlying thrombus in vivo. Our aim was to validate in vivo magnetic resonance imaging (MRI) of the thrombus formation after pharmacological triggering of plaque disruption in the modified Constantinides animal model of plaque disruption. Atherosclerosis was induced in 9 New Zealand White male rabbits (3 kg) with aortic balloon endothelial injury followed by a high cholesterol (1%) diet for 8 weeks. After baseline (pretrigger) MRI, the rabbits underwent pharmacological triggering with Russell's viper venom and histamine, followed by another MRI 48 hours later. Contiguous cross-sectional T2-weighted fast spin echo images of the abdominal aorta were compared by histopathology. In all animals, aortic wall thickening was present on the pretrigger MRI. On MRIs performed 48 hours after triggering, a histologically confirmed intraluminal thrombus was visualized in 6 (67%) of the 9 animals. MRI data correlated with the histopathology regarding aortic wall thickness (R=0.77, P<0.0005), thrombus size (R=0.82, P<0.0001), thrombus length (R=0.86, P<0.005), and anatomic location (R=0.98, P<0.0001). In vivo, MRI reliably determines the presence, location, and size of the thrombus in this animal model of atherosclerosis and plaque disruption. The combination of in vivo MRI and the modified Constantinides animal model could be an important research tool for our understanding of the pathogenesis of acute coronary syndromes.
由于缺乏动物模型以及在体内直接观察斑块和覆盖其上的血栓的能力有限,动脉粥样硬化斑块破裂的过程一直难以监测。我们的目的是在改良的康斯坦丁尼德斯斑块破裂动物模型中,通过药物触发斑块破裂后,验证体内磁共振成像(MRI)对血栓形成的检测能力。对9只新西兰雄性白兔(体重3千克)进行主动脉球囊内皮损伤,随后给予高胆固醇(1%)饮食8周,诱导动脉粥样硬化。在基线(触发前)MRI检查后,用罗素蝰蛇毒和组胺对兔子进行药物触发,48小时后再进行一次MRI检查。通过组织病理学比较腹主动脉连续的横断面T2加权快速自旋回波图像。在所有动物中,触发前的MRI显示主动脉壁增厚。在触发后48小时进行的MRI检查中,9只动物中有6只(67%)可见经组织学证实的管腔内血栓。MRI数据与主动脉壁厚度(R=0.77,P<0.0005)、血栓大小(R=0.82,P<0.0001)、血栓长度(R=0.86,P<0.005)和解剖位置(R=0.98,P<0.0001)的组织病理学结果相关。在这个动脉粥样硬化和斑块破裂的动物模型中,MRI能够可靠地确定体内血栓的存在、位置和大小。体内MRI与改良的康斯坦丁尼德斯动物模型相结合,可能成为我们理解急性冠状动脉综合征发病机制的重要研究工具。