Zweier J L, Chzhan M, Samouilov A, Kuppusamy P
Department of Medicine, Division of Cardiology and the EPR Center, Johns Hopkins University, Baltimore, MD 21224, USA.
Phys Med Biol. 1998 Jul;43(7):1823-35. doi: 10.1088/0031-9155/43/7/002.
It has been hypothesized that free radical metabolism, oxygenation and nitric oxide generation in biological organs such as the heart may vary over the spatially defined tissue structure. To address fundamental questions regarding the role of spatially localized alterations in radical metabolism, oxygenation and nitric oxide in the pathophysiology of cellular injury during ischaemia, we have developed instrumentation optimized for 3D spatial and 3D or 4D spectral-spatial imaging of free radicals in the isolated perfused rat heart at 1.2 GHz. Using this instrumentation, high-quality 3D spectral-spatial imaging of nitroxide metabolism was performed as well as spatially localized measurements of oxygen concentrations, based on the oxygen-dependent linewidth broadening observed. In these spectral-spatial images, submillimetre resolution was observed enabling visualization of the left ventricular and right ventricular myocardium. With 3D spatial imaging using single-line labels, resolutions down to 100 to 200 microm were obtained enabling visualization of the ventricles, aortic root and proximal coronary arteries. Using metal complexes which trap nitric oxide, measurement and imaging of nitric oxide generation during ischaemia was performed. With the use of 15N isotope labelling it was possible to map the metabolic pathway of this nitric oxide generation. Thus, EPR imaging is a powerful tool which can provide unique information regarding the spatial localization of free radicals, oxygen and nitric oxide in biological organs and tissues.
据推测,诸如心脏等生物器官中的自由基代谢、氧合作用和一氧化氮生成可能会在空间定义的组织结构中有所不同。为了解决关于自由基代谢、氧合作用和一氧化氮的空间局部改变在缺血期间细胞损伤病理生理学中作用的基本问题,我们开发了一种仪器,该仪器针对在1.2GHz频率下对离体灌注大鼠心脏中的自由基进行三维空间和三维或四维光谱空间成像进行了优化。使用该仪器,基于观察到的氧依赖性线宽展宽,对氮氧化物代谢进行了高质量的三维光谱空间成像,并对氧浓度进行了空间局部测量。在这些光谱空间图像中,观察到了亚毫米级分辨率,从而能够可视化左心室和右心室心肌。使用单线标记进行三维空间成像时,获得了低至100至200微米的分辨率,从而能够可视化心室、主动脉根部和近端冠状动脉。使用捕获一氧化氮的金属配合物,对缺血期间一氧化氮的生成进行了测量和成像。通过使用15N同位素标记,有可能绘制出这种一氧化氮生成的代谢途径。因此,电子顺磁共振成像(EPR成像)是一种强大的工具,它可以提供有关生物器官和组织中自由基、氧和一氧化氮空间定位的独特信息。