Abstract
Simultaneous assessment of excretory liver and kidney function is still an unmet need in experimental stress models as well as in critical care. The aim of the study was to characterize two polymethine-dyes potentially suitable for this purpose in vivo. Plasma disappearance rate and elimination measurements of simultaneously injected fluorescent dyes DY-780 (hepato-biliary elimination) and DY-654(renal elimination) were conducted using catheter techniques and intravital microscopy in animals subjected to different organ injuries, i.e. polymicrobial sepsis by peritoneal contamination and infection, ischemia-reperfusion-injury and glycerol-induced acute kidney-injury. DY-780 and DY-654 showed organ specific and determined elimination routes in both healthy and diseased animals. They can be measured simultaneously using near-infrared imaging and spectrophotometry. Plasma-disappearance rates of DY-780 and DY-654 are superior to conventional biomarkers in indicating hepatic or kidney dysfunction in different animal models. Greatest impact on liver function was found in animals with polymicrobial sepsis whereas glomerular damage due to glycerol-induced kidney-injury had strongest impact on DY-654 elimination. We therefore conclude that hepatic elimination and renal filtration can be assessed in rodents measuring plasma-disappearance rates of both dyes. Further, assessment of organ dysfunction by polymethine dyes correlates with, but outperforms conventional biomarkers regarding sensitivity and the option of spatial resolution if biophotonic strategies are applied. Polymethine-dye clearance thereby allows sensitive point-of-care assessment of both organ functions simultaneously.
Highlights
(Multi-)organ dysfunction after systemic infection defines sepsis[1] and is one of the most common causes of death in intensive care units worldwide
Their distinct spectral properties allow to simultaneously analyze liver and renal dysfunction in vivo applying plasma-disappearance rate (PDR) measurement in animal models for liver and kidney ischemia-reperfusion (IR) injury, glycerol-induced acute kidney injury (AKI) and a model for sepsis, i.e. peritoneal contamination and infection, which can lead to multiple organ dysfunction and would allow to study the organ-organ interactions critical for the pathophysiology of acute care
indocyanine green (ICG) is already approved as a clinical test to analyze liver function
Summary
(Multi-)organ dysfunction after systemic infection defines sepsis[1] and is one of the most common causes of death in intensive care units worldwide. There is an ongoing search for better diagnostics and new biomarkers such as up-regulated proteins, e.g. neutrophil gelatinase-associated lipocalin (NGAL)[7,8,9], urinary kidney injury molecule (KIM-1)[10,11,12], insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2)[13,14,15] Enzymes measured, such as NAG, a- and p-glutathione s-transferase (GST), γ-glutanyl transpeptidase (γ-GT) and alkaline phosphatase (AP) as well as the functional marker plasma/serum Cystatin C have limited clinical utility:[16] These markers cannot be applied at point-of-care, when immediate assessment of the effect of a treatment is needed. Their distinct spectral properties allow to simultaneously analyze liver and renal dysfunction in vivo applying plasma-disappearance rate (PDR) measurement in animal models for liver and kidney ischemia-reperfusion (IR) injury, glycerol-induced acute kidney injury (AKI) and a model for sepsis, i.e. peritoneal contamination and infection, which can lead to multiple organ dysfunction and would allow to study the organ-organ interactions critical for the pathophysiology of acute care
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
