Characterization of the Murine Septic Response Using Wireless Telemetry Technology

Anthony Lewis, University of Pittsburgh; Christopher Seymour, University of Pittsburgh; Du Yuan, University of Pittsburgh; Matthew Rosengart, University of Pittsburgh

Murine models are commonly utilized in the study of sepsis to test experimental treatments that are administered at fixed intervals after the insult. Yet, sepsis care in humans is prompted not by time on the clock, but by physiologic and behavioral changes that prompt medical care. These animal models ignore the inherent variability in the magnitude and temporality of the host response. Thus, animal models of time-based treatment lack any realistic clinical correlate. We sought to better characterize the murine septic response to cecal ligation and puncture with novel wireless telemetry technology.

We hypothesize that the murine septic response will show a range of variability in mice subjected to cecal ligation and puncture.

C57BL/6J mice aged 8-12 weeks were assigned to either control or cecal ligation and puncture (CLP) groups. CLP was performed using a 1 cm ligation/double 21-gauge puncture method. At the time of CLP, mice in both groups were implanted with a HD-X11 wireless telemetry monitor (Data Sci Intl). This device enables continuous monitoring of core temperature, EKG, and animal foraging activity. Mice were observed and parameters monitored for 24 hours.

During the 24-hour observational period, control mice showed fairly consistent and similar post-procedure recovery and return to physiologic baselines (Figure 1). By contrast, mice subjected to CLP showed considerable heterogeneity in thermoregulation, cardiac physiology, and the sick response to the septic insult (Figure 1). Responses of mice in the CLP group ranged from death within the first 16 hours to mild illness with near-normal vital signs and activity levels. Additionally, mice subjected to CLP began to develop septic states at a variety of time points after surgery.

Considerable heterogeneity in the murine response to CLP sepsis was observed. The testing of experimental treatments at fixed time points after septic insult ignores this variability. The use of continuous wireless telemetric monitoring may enable us to conduct future studies that test treatments at more physiologically relevant time points and that provide data of greater clinical relevance to, and thus guidance of, human trials.