Project Details
Projekt
Effect of different anesthetic agents on lymphatic pumping – an experimental and translational approach
Applicant
Dr. Judith-Elisabeth Riemer
Subject Area
Anaesthesiology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 565674550
INTRODUCTION: Spontaneous contraction of specialized lymphatic muscle cells is key in creating unidirectional flow of fluid from primary lymph vessels back to the circulatory system. This mechanism is called lymphatic pumping and is essential to sustain fluid homeostasis. Inflammatory signaling events and certain medications, like anesthetic agents, can disrupt this system and subsequently cause severe complications, such as edema or hypovolemia. However, it is still unknown which anesthetic agents specifically cause lymphoplegia and what mechanisms are the reason for this phenomenon. Additionally, there is a significant lack of technology for accurate measurements of lymphatic function in humans. AIMS: This proposed project aims to investigate the impact of different anesthetic agents (isoflurane, propofol and ketamine) on lymphatic pumping in a murine model of intensive care, specifically focusing on the role of the sympathetic nervous system (SNS) (AIMs 1 and 2). It further addresses the need of functional imaging tools in an approach to translate near-infrared (NIR) lymphangiography from mice to human subjects (AIM 3). METHODS: In AIM 1 and 2, an already established murine model of critical care will be utilized. Mice will be anesthetized with isoflurane, propofol or ketamine and the positive end-expiratory pressure (PEEP) and oxygen saturation (SpO2) will be monitored. Lymphatic pumping will then be measured using live NIR lymphangiography and data will be analyzed using MATLAB. In experiments of AIM 3, brachial indocyanine green (ICG) injections will be performed in a group of 20 healthy volunteers, followed by NIR lymphangiography recordings. Measurements will be conducted in three different positions (baseline, up and down) for 5 minutes each and will be repeated on the contralateral arm. Recordings will again be analyzed using MATLAB. IMPACT: The knowledge, which anesthetic agents might effect the lymphatic function is crucial, in order to establish better, more individualized choices regarding the anesthetic regimen based on the clinical need of the patients. Elucidating whether the SNS might mediate this effect could help develop therapeutic strategies (e.g. using vasoactive agents to counteract inhibitory effects). In addition, establishing a reliable and non-invasive method to assess human lymphatic function would promote the field of lymphatic medicine even more. This could allow for future investigations evaluating the effect of pharmacologic agents (e.g. general anesthesia) or pathophysiological processes (like inflammation and septic shock) on the human lymphatic function.
DFG Programme
WBP Fellowship
International Connection
USA
