nam 22 uu 4500 dbt_mods_00054007 10.3389/fphys.2021.733868 doi dbt_mods_00054007 ger DE-601 rda eng 610 sdnb Christ, Bruno Author aut Cell Transplantation/Molecular Hepatology Lab, Department of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Center ,Leipzig ,Germany Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function Christ, Bruno;Collatz, Maximilian;Dahmen, Uta;Herrmann, Karl-Heinz;Höpfl, Sebastian;König, Matthias;Lambers, Lena;Marz, Manja;Meyer, Daria;Radde, Nicole;Reichenbach, Jürgen R.;Ricken, Tim;Tautenhahn, Hans-Michael 2021-11-18 34 Seiten text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Zweitveröffentlichung Liver resection causes marked perfusion alterations in the liver remnant both on the organ scale (vascular anatomy) and on the microscale (sinusoidal blood flow on tissue level). These changes in perfusion affect hepatic functions via direct alterations in blood supply and drainage, followed by indirect changes of biomechanical tissue properties and cellular function. Changes in blood flow impose compression, tension and shear forces on the liver tissue. These forces are perceived by mechanosensors on parenchymal and non-parenchymal cells of the liver and regulate cell-cell and cell-matrix interactions as well as cellular signaling and metabolism. These interactions are key players in tissue growth and remodeling, a prerequisite to restore tissue function after PHx. Their dysregulation is associated with metabolic impairment of the liver eventually leading to liver failure, a serious post-hepatectomy complication with high morbidity and mortality. Though certain links are known, the overall functional change after liver surgery is not understood due to complex feedback loops, non-linearities, spatial heterogeneities and different time-scales of events. Computational modeling is a unique approach to gain a better understanding of complex biomedical systems. This approach allows (i) integration of heterogeneous data and knowledge on multiple scales into a consistent view of how perfusion is related to hepatic function; (ii) testing and generating hypotheses based on predictive models, which must be validated experimentally and clinically. In the long term, computational modeling will (iii) support surgical planning by predicting surgery-induced perfusion perturbations and their functional (metabolic) consequences; and thereby (iv) allow minimizing surgical risks for the individual patient. Here, we review the alterations of hepatic perfusion, biomechanical properties and function associated with hepatectomy. Specifically, we provide an overview over the clinical problem, preoperative diagnostics, functional imaging approaches, experimental approaches in animal models, mechanoperception in the liver and impact on cellular metabolism, omics approaches with a focus on transcriptomics, data integration and uncertainty analysis, and computational modeling on multiple scales. Finally, we provide a perspective on how multi-scale computational models, which couple perfusion changes to hepatic function, could become part of clinical workflows to predict and optimize patient outcome after complex liver surgery. multi-scale modeling liver regeneration liver surgery liver perfusion perfusion/function relationship mechanoperception rodent models of liver surgery article Collatz, Maximilian Author aut RNA Bioinformatics and High-Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena Optisch-Molekulare Diagnostik und Systemtechnologié, Leibniz Institute of Photonic Technology (IPHT) ,Jena ,Germany InfectoGnostics Research Campus Jena ,Jena ,Germany (DE-588)1214760317 Dahmen, Uta Author aut Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Jena University Hospital (DE-588)114498405X Herrmann, Karl-Heinz Author aut Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital (DE-588)123420628 Höpfl, Sebastian Author aut Faculty of Engineering Design, Production Engineering and Automotive Engineering, Institute for Systems Theory and Automatic Control, University of Stuttgart ,Stuttgart ,Germany König, Matthias Author aut Systems Medicine of the Liver Lab, Institute for Theoretical Biology, Humboldt-University Berlin ,Berlin ,Germany Lambers, Lena Author aut Faculty of Aerospace Engineering and Geodesy, Institute of Mechanics, Structural Analysis and Dynamics, University of Stuttgart ,Stuttgart ,Germany Marz, Manja Author aut RNA Bioinformatics and High-Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena (DE-588)140462732 Meyer, Daria Author aut RNA Bioinformatics and High-Throughput Analysis, Faculty of Mathematics and Computer Science, Friedrich Schiller University Jena (DE-588)122155493X Radde, Nicole Author aut Faculty of Engineering Design, Production Engineering and Automotive Engineering, Institute for Systems Theory and Automatic Control, University of Stuttgart ,Stuttgart ,Germany Reichenbach, Jürgen R. Author aut Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital (DE-588)172628067 Ricken, Tim Author aut Faculty of Aerospace Engineering and Geodesy, Institute of Mechanics, Structural Analysis and Dynamics, University of Stuttgart ,Stuttgart ,Germany Tautenhahn, Hans-Michael Author aut Department of General, Visceral and Vascular Surgery, Jena University Hospital (DE-588)1044672463 Friedrich-Schiller-Universität Jena Medizinische Fakultät host institution his 12:733868 Technische Universität Ilmenau, Universitätsbibliothek Frontiers in physiology 1664-042X dbt_mods_00038737 https://www.db-thueringen.de/receive/dbt_mods_00054007 object in context https://www.db-thueringen.de/servlets/MCRFileNodeServlet/dbt_derivate_00057769/fphys-12-733868.pdf raw object https://www.db-thueringen.de/rsc/thumbnail/dbt_mods_00054007.png preview https://www.db-thueringen.de/receive/dbt_mods_00054007 uri