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 nearinfrared fluorophore, ZW8001, to assess renal and cardiac function. We performed murine cardiac arrest and cardiopulmonary resuscitation followed by transthoracic echocardiography, 2 and 24h later. Transcutaneous fluorescence of ZW8001 bolus dispersion and clearance was assessed with wholeanimal imaging and compared with glomerular filtration rate (GFR, inulin clearance), tubular cell death (using unbiased stereology), and serum creatinine. Correlation, Bland-Altman, and polar analysis 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 six-fold increase in serum creatinine 24h later (n=16, p<0.01). ZW800-1 biodistribution and clearance was exclusively renal. ZW8001 t1/2 and clearance correlated with GFR (r=0.92, n=31, p<0.0001). ZW8001 fluorescence was reduced in cardiac arrest and cardiopulmonary resuscitation-treated mice compared to sham animals 810s 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 leads to experimental cardiorenal syndrome type 1. ZW8001, a small near infrared fluorophore being developed for clinical intraoperative imaging is favorable for evaluating cardiac and renal function noninvasively.
- glomerular filtration rate
- acute kidney injury
- near-infrared fluorophore
- Copyright © 2016, American Journal of Physiology-Renal Physiology