Faculty Collaboration Database

Fluorescein clearance kinetics in blood and bile indicates hepatic ischemia-reperfusion injury in rats. Am J Physiol Gastrointest Liver Physiol 2022 Aug 01;323(2):G126-G133

Date

06/15/2022

Pubmed ID

35700191

DOI

10.1152/ajpgi.00038.2022

Scopus ID

2-s2.0-85134761396 (requires institutional sign-in at Scopus site)   1 Citation

Abstract

Quantitative measurement of the degree of hepatic ischemia-reperfusion injury (IRI) is crucial for developing therapeutic strategies for its treatment. We hypothesized that clearance of fluorescent dye through bile metabolism may reflect the degree of hepatic IRI. In this study, we investigated sodium fluorescein clearance kinetics in blood and bile for quantifying the degree of hepatic IRI. Warm ischemia times (WITs) of 0, 30, or 60 min followed by 1 h or 4 h of reperfusion, were applied to the median and lateral lobes of the liver in Sprague-Dawley rats. Subsequently, 2 mg/kg of sodium fluorescein was injected intravenously, and blood and bile samples were collected over 60 min to measure fluorescence intensities. The bile-to-plasma fluorescence ratios demonstrated an inverse correlation with WIT and were distinctly lower in the 60-min WIT group than in the control or 30-min WIT groups. Bile-to-plasma fluorescence ratios displayed superior discriminability for short versus long WITs when measured 1 h after reperfusion versus 4 h. We conclude that the bile-to-blood ratio of fluorescence after sodium fluorescein injection has the potential to enable the quantification of hepatic IRI severity.NEW & NOTEWORTHY Previous attempts to use fluorophore clearance to test liver function have relied on a single source of data. However, the kinetics of substrate processing via bile metabolism include decreasing levels in blood and increasing levels in bile. Thus, we analyzed data from blood and bile to better reflect fluorescein clearance kinetics.

Author List

Kim J, Yang Y, Hong SK, Zielonka J, Dash RK, Audi SH, Kumar SN, Joshi A, Zimmerman MA, Hong JC

Authors

Said Audi PhD Professor in the Biomedical Engineering department at Marquette University
Ranjan K. Dash PhD Professor in the Biomedical Engineering department at Medical College of Wisconsin
Seung-Keun Hong PhD Research Scientist II in the Surgery department at Medical College of Wisconsin
Amit Joshi PhD Professor in the Biomedical Engineering department at Medical College of Wisconsin
Joohyun Kim MD, PhD Associate Professor in the Surgery department at Medical College of Wisconsin
Suresh Kumar PhD Associate Professor in the Pathology department at Medical College of Wisconsin
Jacek M. Zielonka PhD Assistant Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Bile
Fluorescein
Kinetics
Liver
Rats
Rats, Sprague-Dawley
Reperfusion Injury