Clinician Scientist-Programm 2022

Thema: "Impact of surgery-related impaired hepatic perfusion on function and regeneration of the remnant liver. A translational study on rats and patients."

Zusammenfassung:
Patients subjected to extended liver resection are at risk of postoperative liver failure, which is potentiated by the hyperperfusion state of the liver. Therefore, it is important to quantify the risk of postoperative liver failure for the individual patient. So far, the complex interplay between changes in liver volume, liver perfusion and hepatic functions, especially in the clinical context of liver resection, has not been in the focus of research. We hypothesize that liver size and liver function are not necessarily proportional, not even in healthy livers undergoing resection. We will perform an experimental study in rats in parallel to a small exploratory clinical study. Based on well-established MR-imaging techniques, we will quantify liver volume, perfusion, regeneration and function in vivo before and at defined time points after surgery. In addition, liver regeneration and function will be investigated in vitro by quantifying hepatocyte proliferation rate and distribution, as well as the expression level of proliferation related proteins. Liver function will be assessed in terms of expression level, distribution and activity of the drug metabolizing enzyme cytochrome p450 (CYP) 1A2. Distribution of proteins will be assessed using immunohistochemistry, expression levels based on western blots and CYP activity with the help of spectrophotometric assay.