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A comprehensive approach to visual and functional assessment of experimental vascular lesions in vivo.

机译:一种对体内实验性血管病变进行视觉和功能评估的综合方法。

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The rat carotid injury model is the most widely used model to study the pathophysiology of neointimal hyperplasia as well as the value of novel therapeutic approaches to limit vasoproliferative diseases such as restenosis. For lesion assessment, the current gold standard of histomorphometry neither provides integral insight into the vascular lesion in vivo nor assesses of functional lesion-associated flow alterations and the time course of lesion development. To overcome these limitations, we applied and validated duplex sonography as a novel tool for comprehensive lesions assessment in vivo. Left rat common carotid arteries (CCA) were balloon injured. Duplex sonography was performed in both injured and noninjured CCAs before and up to 14 days postinjury. Sham-operated animals served as controls. The parameters determined were vessel lumen diameter as well as systolic and end-diastolic flow velocity, time-dependent lesion development, and intra- and interobserver variability. Subsequently, the model was applied to validate the therapeutic effect of gene transfer into the vessel wall and compared with histomorphometry. We show that duplex sonography in the experimental carotid injury model allows accurate follow-up of lesion development in vivo with low intra- and interobserver variability. It can be easily adopted to assess the efficacy of therapeutic approaches even with limited technical experience and adds valuable functional data to mere postmortem histomorphometric analysis, thereby closing the gap between experimental approaches and clinical importance of vascular lesions.
机译:大鼠颈动脉损伤模型是研究新内膜增生的病理生理以及限制血管增生性疾病(如再狭窄)的新型治疗方法的价值的最广泛使用的模型。对于病灶评估,当前的组织形态计量学金标准既不能提供对体内血管病灶的完整了解,也不能评估功能性病灶相关的血流改变和病灶发展的时程。为了克服这些局限性,我们应用并验证了双工超声作为一种新颖的工具,可以在体内进行全面的病变评估。左大鼠颈总动脉(CCA)球囊受伤。在受伤前和受伤后14天,均在受伤和未受伤的CCA中进行了双重超声检查。假手术动物作为对照。确定的参数是血管内腔直径以及收缩和舒张末期流速,随时间变化的病变发展以及观察者内和观察者间的变异性。随后,该模型用于验证基因转移至血管壁的治疗效果,并与组织形态计量学进行比较。我们显示,在实验性颈动脉损伤模型中进行双工超声检查,可以在体内观察到的和观察者之间的变异性低的情况下,对病灶发展进行准确的随访。即使在技术经验有限的情况下,也可以很容易地采用它来评估治疗方法的有效性,并且仅在事后组织形态分析中就可以添加有价值的功能数据,从而缩小了实验方法与血管病变的临床重要性之间的差距。

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