Anesthesiology and Perioperative Medicine, Oregon Health & Science University, Portland, Oregon.
Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts.
Am J Physiol Renal Physiol. 2017 Apr 1;312(4):F629-F639. doi: 10.1152/ajprenal.00573.2016. Epub 2017 Jan 11.
Cardiorenal syndrome type 1 causes acute kidney injury but is poorly understood; animal models and diagnostic aids are lacking. Robust noninvasive measurements of glomerular filtration rate are required for injury models and clinical use. Several have been described but are untested in translational models and suffer from biologic interference. We developed a mouse model of cardiorenal syndrome and tested the novel near-infrared fluorophore ZW800-1 to assess renal and cardiac function. We performed murine cardiac arrest and cardiopulmonary resuscitation followed by transthoracic echocardiography, 2 and 24 h later. Transcutaneous fluorescence of ZW800-1 bolus dispersion and clearance was assessed with whole animal imaging and compared with glomerular filtration rate (GFR; inulin clearance), tubular cell death (using unbiased stereology), and serum creatinine. Correlation, Bland-Altman, and polar analyses were used to compare GFR with ZW800-1 clearance. Cardiac arrest and cardiopulmonary resuscitation caused reversible cardiac failure, halving fractional shortening of the left ventricle ( = 12, = 0.03). Acute kidney injury resulted with near-zero GFR and sixfold increase in serum creatinine 24 h later ( = 16, < 0.01). ZW800-1 biodistribution and clearance were exclusively renal. ZW800-1 and clearance correlated with GFR ( = 0.92, = 31, < 0.0001). ZW800-1 fluorescence was reduced in cardiac arrest, and cardiopulmonary resuscitation-treated mice compared with sham animals 810 s after injection ( < 0.01) and bolus time-dispersion curves demonstrated that ZW800-1 fluorescence dispersion correlated with left ventricular function ( = 0.74, < 0.01). Cardiac arrest and cardiopulmonary resuscitation lead to experimental cardiorenal syndrome type 1. ZW800-1, a small near-infrared fluorophore being developed for clinical intraoperative imaging, is favorable for evaluating cardiac and renal function noninvasively.
1 型心肾综合征导致急性肾损伤，但人们对此了解甚少；缺乏动物模型和诊断辅助工具。损伤模型和临床应用需要稳健的、非侵入性的肾小球滤过率测量方法。已经描述了几种方法，但在转化模型中尚未经过测试，并且存在生物学干扰。我们开发了一种 1 型心肾综合征的小鼠模型，并测试了新型近红外荧光染料 ZW800-1，以评估肾脏和心脏功能。我们进行了小鼠心脏骤停和心肺复苏，然后在 2 小时和 24 小时后进行经胸超声心动图检查。使用小动物成像评估 ZW800-1 团注弥散和清除的经皮荧光，并与肾小球滤过率（菊粉清除率）、肾小管细胞死亡（使用无偏立体学）和血清肌酐进行比较。使用相关分析、Bland-Altman 分析和极坐标分析比较 GFR 与 ZW800-1 清除率。心脏骤停和心肺复苏导致可逆性心力衰竭，左心室短轴缩短率减半（ = 12， = 0.03）。急性肾损伤导致肾小球滤过率几乎为零，24 小时后血清肌酐增加六倍（ = 16， < 0.01）。ZW800-1 的生物分布和清除仅为肾脏。ZW800-1 与 GFR 相关（ = 0.92， = 31， < 0.0001）。与假手术组相比，ZW800-1 荧光在心脏骤停和心肺复苏治疗的小鼠中分别在注射后 810 秒（ < 0.01）和团注时间弥散曲线中减少，并且 ZW800-1 荧光弥散与左心室功能相关（ = 0.74， < 0.01）。心脏骤停和心肺复苏导致实验性 1 型心肾综合征。ZW800-1 是一种为临床术中成像而开发的小型近红外荧光染料，非常适合非侵入性评估心脏和肾脏功能。
