# The Impact of Anesthetics on Lymphatic Vessel Contractility and Extracellular Fluid Uptake

> **NIH NIH K08** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $197,080

## Abstract

Project Summary / Abstract
The lymphatic system, integral to fluid balance, fat absorption, and immunity, actively propels lymph fluid via
specialized lymphatic muscle cells (LMCs) and coordinated contractile behavior. Lymphatic vessels play a crucial
role in maintaining fluid balance. The entire plasma volume extravasates from the blood roughly every 9 hours
and is reclaimed by the lymphatic system and returned to the central circulation. Disruption to lymphatic function,
from factors like inflammation or medications, can lead to edema. In critical illness, edema increases morbidity
and mortality. Despite extensive use of anesthetics like isoflurane, propofol, ketamine, and dexmedetomidine,
their impact on lymphatic function remains unknown. In this innovative proposal, the goal is to study the impact
of these anesthetics on lymphatic function using advanced lymphatic functional imaging techniques in a novel
murine model of critical care. The translational model includes tracheostomy, controlled mechanical ventilation,
an intra-arterial line, a central venous catheter for infusion of drugs, and vital sign monitoring. This is combined
with three imaging modalities: intravital fluorescence lymphangiography to quantitatively measure lymphatic
contractions, intravital near infrared fluorescence lymphangiography to measure lymphatic network behavior,
and a novel bioluminescent assay to quantify the rate of clearance of interstitial fluid. In Aim 1, experiments will
probe the effects of various anesthetics on lymphatic contractility in a critical care mouse model. Both systemic
influences and direct vascular effects of anesthetics on lymphatic function and fluid clearance will be measured.
Electrophysiology will complement in vivo lymphatic imaging to directly observe changes in LMC excitability
mediated by anesthetics. In Aim 2, the study will explore the relationship between anesthetics and lymphatic
adrenergic receptor activation, examining whether anesthetics influence lymphatic contractility via the
sympathetic nervous system, the potential functional rescue effects of norepinephrine, and the distribution of
adrenergic receptors in human lymphatic tissue. The proposed research aspires to profoundly shape future
clinical practice by elucidating the impact of anesthetics on lymphatic pumping and tissue edema. This will allow
for future tailored anesthetic selection in the operating room and intensive care unit based on the patient’s level
of edema. The Mentored Clinical Scientist Research Career Development Award candidate, an MD, PhD with a
research background in electrophysiology and lymphatics, serves as an anesthesiologist and intensivist at
Massachusetts General Hospital and is dedicated to advancing an academic trajectory in translational research.
An expert mentorship team in lymphatic imaging (Dr. Padera, PhD), instrumented mouse models (Dr. Ichinose,
MD, PhD), and electrophysiology (Dr. Logothetis, PhD) will help the candidate combine thes...

## Key facts

- **NIH application ID:** 10949288
- **Project number:** 1K08GM155886-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Katarina J Ruscic
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $197,080
- **Award type:** 1
- **Project period:** 2024-09-01 → 2030-01-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10949288

## Citation

> US National Institutes of Health, RePORTER application 10949288, The Impact of Anesthetics on Lymphatic Vessel Contractility and Extracellular Fluid Uptake (1K08GM155886-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10949288. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*