165 Label-free autofluorescence lifetime to assess changes in myocardial fibrosis and metabolism in vivo in a doxorubicin cardiomyopathy heart failure model
165 Label-free autofluorescence lifetime to assess changes in myocardial fibrosis and metabolism in vivo in a doxorubicin cardiomyopathy heart failure model
复制标题
165 无标记自发荧光寿命评估阿霉素心肌病心力衰竭模型中心肌纤维化和体内代谢的变化
DOI：
10.1136/heartjnl-2015-308066.165
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发表时间：
2015
期刊：
影响因子：
5.7
通讯作者：
Dyer B
中科院分区：
文献类型：
--
作者：
Dyer B
我们正在开发一种基于自体荧光（AFL）寿命的技术，以确定与心肌疾病的组织学，代谢和功能变化相关的签名。AFL光谱利用了许多内源性分子的特性，并提供了避免可能改变生理环境的外源性标记物使用的可能性。分子如NADH和黄素的AFL测量可以报告能量状态的变化，而来自基质如胶原蛋白的特征可以报告结构改变。我们研究了一种基于光纤的单点仪器结合时间分辨荧光光谱和漫反射光谱的应用程序，阿霉素心肌病心力衰竭模型（DOX-HF）在vivo.Sprague-Dawley雄性大鼠接受1.25 mg/kg阿霉素或溶剂（0.9%氯化钠）通过尾静脉注射每周8周。一旦心力衰竭表型建立良好，在第11周体内测量AFL信号。DOX-HF（n = 8）LVEF为49.6%，对照组为80.4%（n = 4）（**p = 0.006）。在11周时，在LV、RV和LV后壁中观察到DOX-HF（n = 6）和对照（n = 3）之间的AFL信号的显著差异（*p < 0.05）。在DOX-HF（n = 6）中与对照（n = 3）相比，在所有区域中观察到胶原AFL的比例显著增加（*p < 0.05）。AFL预测的胶原含量先前与定量组织学高度相关（r = 0.984，*p < 0.05）。并入冠状动脉导管或起搏电极导线可以提供额外的诊断信息和监测。早期变化的识别可以允许开发一种筛查策略，以识别发展为心肌病的癌症患者，从而允许明智地调整化疗。
We are developing an autofluorescence (AFL) lifetime-based technique to characterise the signatures associated with histological, metabolic and functional changes in myocardial disease. AFL spectroscopy exploits the properties of a number of endogenous molecules and offers the potential to avoid exogenous label use that could potentially alter the physiological environment. AFL measurements of molecules such as NADH and flavins may report energetic state changes, whilst signatures from matrix such as collagen inform of structural alterations. We investigated the application of a fibre-optic based single-point instrument combining time-resolved spectrofluorometry and diffuse reflectance spectroscopy to a doxorubicin cardiomyopathy heart failure model (DOX-HF)in vivo.Sprague-Dawley male rats received 1.25 mg/kg doxorubicin or vehicle (0.9% NaCl) via tail vein injection weekly for 8 weeks. AFL signals were measuredin vivoin week 11, once heart failure phenotype was well established. DOX-HF(n = 8) LVEF 49.6% vs. 80.4% in controls (n = 4)(**p = 0.006). At 11 weeks, significant differences in AFL signals between DOX-HF(n = 6) and control (n = 3) in LV, RV and LV posterior wall were observed (*p < 0.05). A significantly increased proportion of collagen AFL was seen across all areas in DOX-HF (n = 6) vs. control (n = 3)(*p < 0.05). AFL-predicted collagen content was previously highly correlated with quantitative histology (r = 0.984,*p < 0.05).Our instrument has sensitivity to characterisein vivochanges in DOX-HF model without use of exogenous compounds. Incorporation into coronary catheters or pacing leads could offer additional diagnostic information and monitoring. Identification of earlier changes could permit development of a screening strategy to identify cancer patients developing cardiomyopathy to permit judicious adjustment of chemotherapy.