Determination of renal function and injury using near-infrared fluorimetry in experimental cardiorenal syndrome
Determination of renal function and injury using near-infrared fluorimetry in experimental cardiorenal syndrome
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DOI：
10.1152/ajprenal.00573.2016
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发表时间：
2017-04-01
影响因子：
4.2
通讯作者：
Hutchens, Michael P.
中科院分区：
文献类型：
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作者：
Ikeda, Mizuko;Wakasaki, Rumie;Hutchens, Michael P.
1 型心肾综合征会导致急性肾损伤，但人们对此知之甚少；缺乏动物模型和诊断辅助工具。损伤模型和临床应用需要对肾小球滤过率进行稳健的无创测量。有几种已经被描述，但未经转化模型测试，并且受到生物干扰。我们开发了心肾综合征小鼠模型，并测试了新型近红外荧光团 ZW800-1 以评估肾脏和心脏功能。我们对小鼠进行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。通过整体动物成像评估 ZW800-1 丸剂分散和清除的经皮荧光，并与肾小球滤过率（GFR；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。使用相关性、Bland-Altman 和极性分析来比较 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，左心室缩短分数减半（n = 12，P = 0.03）。急性肾损伤导致 GFR 接近于零，24 小时后血清肌酐增加六倍（n = 16，P = 0.01）。 ZW800-1 的生物分布和清除完全是肾脏的。 ZW800-1 t(1/2) 和清除率与 GFR 相关（r = 0.92，n = 31，P < 0.0001）。注射后 810 秒，与假手术动物相比，心脏骤停和心肺复苏治疗的小鼠 ZW800-1 荧光减弱（P < 0.01），推注时间色散曲线表明 ZW800-1 荧光色散与左心室功能相关（r = 0.74，P < 0.01）。心脏骤停和心肺复苏会导致实验性心肾综合征 1 型。ZW800-1 是一种用于临床术中成像的小型近红外荧光团，有利于无创评估心脏和肾功能。
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 (n = 12, P = 0.03). Acute kidney injury resulted with near-zero GFR and sixfold increase in serum creatinine 24 h later (n = 16, P = 0.01). ZW800-1 biodistribution and clearance were exclusively renal. ZW800-1 t(1/2) and clearance correlated with GFR (r = 0.92, n = 31, P < 0.0001). ZW800-1 fluorescence was reduced in cardiac arrest, and cardiopulmonary resuscitation-treated mice compared with sham animals 810 s after injection (P < 0.01) and bolus time-dispersion curves demonstrated that ZW800-1 fluorescence dispersion correlated with left ventricular function (r = 0.74, P < 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.