PD19-04 A NOVEL, HIGH-THROUGHPUT UROSEPSIS MOUSE MODEL

Abstract

You have accessJournal of UrologyCME1 Apr 2023PD19-04 A NOVEL, HIGH-THROUGHPUT UROSEPSIS MOUSE MODEL Roman Herout, Sreeparna Vappala, Sarah Hanstock, Igor Moskalev, Ben H. Chew, Jayachandran N. Kizhakkedathu, and Dirk Lange Roman HeroutRoman Herout More articles by this author , Sreeparna VappalaSreeparna Vappala More articles by this author , Sarah HanstockSarah Hanstock More articles by this author , Igor MoskalevIgor Moskalev More articles by this author , Ben H. ChewBen H. Chew More articles by this author , Jayachandran N. KizhakkedathuJayachandran N. Kizhakkedathu More articles by this author , and Dirk LangeDirk Lange More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003285.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Murine models of sepsis, such as the cecal ligation and puncture (CLP) model, are typically polymicrobial and associated with a high mortality within hours after the specific intervention. Our aim was to develop a high-throughput, murine model that mimics a slow-paced, monomicrobial sepsis originating from the urinary tract. METHODS: 12-week-old male C57Bl/6 mice (n=23) underwent percutaneous insertion of a 4mm catheter piece into the urinary bladder. The following day Proteus mirabilis (PM) was introduced percutaneously into the bladder in 3 groups: group 1-50 μl of a 1x108 CFU/ml solution (n=10), group 2-50 μl of a 1x107 CFU/ml solution (n=10), and group 3 (sham mice)-50 μl of sterile saline (n=3). On day 4 mice were sacrificed. The number of bacteria in urine, adherent to bladder catheters, adherent to/invaded into the bladder tissue as well as a set of 32 pro-/anti-inflammatory cytokines and chemokines were analyzed. RESULTS: All 23 mice survived the postinterventional period. Mean weight loss was 11% in group 1, 9% in group 2 and 2% in the control group. Mean urine CFU counts were highest in group 1 and all sham mice had negative urine samples. All infected mice had high catheter-adhered bacterial counts. 18/20 infected mice had CFU counts in homogenized splenic tissue indicating septicemia. Cell-free DNA and D-Dimer was highest in group 1 and lowest in the control group. Serum levels of G-CSF were significantly increased in group 1 when compared to controls. Serum levels of IL-6, TNF-α, IFN-γ and IL-1β were all elevated (1.5 to 30-fold) compared to control mice. CONCLUSIONS: We present an easily reproducible, monomicrobial murine model of urosepsis that does not lead to rapid deterioration and death and can therefore be used as a model for prolonged urosepsis. Source of Funding: Roman Herout was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 447437311 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e578 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Roman Herout More articles by this author Sreeparna Vappala More articles by this author Sarah Hanstock More articles by this author Igor Moskalev More articles by this author Ben H. Chew More articles by this author Jayachandran N. Kizhakkedathu More articles by this author Dirk Lange More articles by this author Expand All Advertisement PDF downloadLoading ...