Dr. Ruscic’s Research

The Effects of Anesthetics on Lymphatic Vessel Contractility

Systemic lymphatic dysfunction is rarely considered in critically ill patients with tissue edema. However, the lymphatics reclaim 8L of plasma to the circulation each day to maintain fluid homeostasis. To do this, lymphatic vessels have spontaneous contractile behavior which can be decreased during inflammation or infection. This study will explore the effects of commonly used anesthetics on lymphatic contractility and the interaction of the sympathetic nervous system (SNS) with these effects. Hypothesis 1: isoflurane and propofol decrease lymphatic pumping while ketamine increases it, Hypothesis 2: these phenomena are due to systemic effects rather than direct effects on lymphatic vasculature, Hypothesis 3: pharmacologic manipulation of SNS-lymphatic vessel signaling will modify the effects of isoflurane, propofol and ketamine on lymphatic pumping. 

This study explores novel consequences of anesthetic exposure with critical implications for fluid balance in patients.  These effects could be even more profound with prolonged exposure to anesthetics, such as in critical illness.

Related Publications

A multiresolution approach with method-informed statistical analysis for quantifying lymphatic pumping dynamics
Mohammad S. Razavi, Katarina J. Ruscic, et al.

Despite significant strides in lymphatic system imaging, the timely diagnosis of lymphatic disorders remains elusive. This elusiveness is driven by the absence of standardized, non-invasive, reliable, quantitative methods for real-time functional analysis of lymphatic contractility with adequate spatial and temporal resolution. The authors address this unmet need by integrating near-infrared fluorescence lymphangiography imaging with an innovative analytical workflow that combines data acquisition, signal processing, and statistical analysis to integrate traditional peak-and-valley analysis with advanced wavelet time-frequency analyses. This approach significantly boosts measurement reliability by incorporating multiple regions of interest and evaluating the lymphatic system under various gravitational loads. Improved imaging and quantification methods allowed researchers to offer a new standard approach for the imaging and analysis of lymphatic function that can improve understanding, diagnosis, and treatment of lymphatic diseases. The results highlight the importance of comprehensive data acquisition strategies to fully capture the dynamic behavior of the lymphatic system.

Aging-induced changes in lymphatic muscle cell transcriptomes are associated with reduced pumping of peripheral collecting lymphatic vessels in mice
Pin-Ji Lei, Katarina J. Ruscic, et al.

Lymphatic muscle cells (LMCs) within the wall of collecting lymphatic vessels exhibit tonic and autonomous phasic contractions, which drive active lymph transport to maintain tissue-fluid homeostasis and support immune surveillance. Damage to LMCs disrupts lymphatic function and is related to various diseases. Despite their importance, knowledge of the gene transcriptional signatures in LMCs and how they relate to lymphatic function in normal and disease contexts is largely missing. The authors generated a comprehensive transcriptional single-cell atlas—including LMCs—of peripheral collecting lymphatic vessels from mice across the lifespan. They identified genes that distinguish LMCs from other types of muscle cells, characterized the phenotypical and transcriptomic changes in LMCs in aged vessels, and identified a proinflammatory microenvironment that suppresses the contractile apparatus in LMCs from advanced-aged mice. The findings provide a valuable resource to accelerate future research for the identification of potential drug targets on LMCs to improve lymphatic vessel function.