Whether you are working with in vivo pharmacology, toxicology, basic physiology, or another in vivo field, catheter models are probably one of the most versatile and valuable tools you can add to your experimental line-up.
Most catheter models can be set up with swivels and tethers, which allows the animals to move around freely in the cage for the duration of the entire study. Using the infusion equipment from Instech combined with the high-precision syringe pumps from Harvard Bioscience, I have worked with countless different configurations for short-term or chronic vascular access.
Some of the applications I have experience with are described here, but the list is far from exhaustive, so don't hesitate to reach out to discuss your specific needs.
The gold-standard technique for evaluating whole-body and tissue-specific insulin action. The freely moving dual-catheter model requires implantation of catheters in the jugular vein and carotid artery, respectively. Involves a complex infusion/sampling setup for three simultaneous IV infusions (insulin, glucose, and tracers) and frequent arterial blood sampling. At the annual glucose clamp course (GCC) at RRSSC we teach the whole procedure from surgery to data analysis and reporting. For more information about the GCC, please visit the RRSSC course page here.
Studying metabolic flux requires steady infusion of stable isotope-labeled tracers (typically 13C and 2H) combined with regular collection of blood samples which are subjected to metabolomic analyses. There are numerous different flux models available utilizing different combinations of labeled metabolites which will allow mapping of metabolic processes in vivo in extraordinary detail. The dual-catheter infusion/sampling setup used for the glucose clamp is also perfectly suited for running metabolic flux studies.
When studying systemic effects of interventions targeting specific organs or tissues, transfusion of conditioned serum or plasma from experimental animals to naïve recipients provides an elegant approach to distinguish organ crosstalk through secreted circulating factors from central signaling pathways. A catheter in the jugular or femoral vein of the recipient animals will allow for IV transfusion of considerable volumes of conditioned serum or plasma either acutely or repeatedly over extended periods.
If you need long-term dosing, a catheter model provides a convenient and robust approach for reliable and reproducible delivery of compounds with minimal stress to the animals. There is no need for restraint or use of needles when dosing, and there will be no more injections missing the target. All common routes of delivery can be accommodated, with jugular/femoral vein catheters for IV delivery, gastric catheters for oral delivery, or catheters in the abdominal cavity or subcutaneous space for IP and SC delivery, respectively. Whether used for intermittent bolus-dosing or long-term continuous infusion, these models enable study designs spanning up to several months of delivery of any fluid, for example experimental compounds, tracers, or liquid diets.
Through my role in establishing a state-of-the-art Rodent Metabolic Phenotyping unit, I have gained extensive experience with implementation and operation of several advanced technologies for continuous physiological monitoring.
Implantable telemetry is the ideal technique for measuring physiological parameters in high resolution without human interference. Depending on the choice of implant, measures such as blood glucose, respiratory rate, blood pressure, ECG, EEG, EMG, body temperature, and activity can be readily obtained over extended periods spanning weeks to months. I have designed and executed numerous studies using the PhysioTel HD system,and developed integrations with other technologies, such as synchronized food intake monitoring or freely moving infusion/sampling models, which expands the experimental capabilities of the system tremendously.
Based on RFID technology, the Mouse Matrix offers long-term continuous monitoring of activity and body temperature in individual mice in social housing. Unlike traditional RFID systems, which rely on handheld readers for manual scanning, the Mouse Matrix plates are placed under the cages and scans continuously in high resolution. Due to the small size of the RFID transponders and the minimally invasive insertion procedure, mice can be chipped at a very early age, and since there are no batteries or sensor degradation in the transponders, monitoring can proceed for the entire life of the animal. Taking advantage of the small chip size, and the support for multiple chips by the plates, I have adapted the system to establish a model, where surgical implantation of up to three transponders in the same animal allows for measurement of regional temperature differences. Using this model for high-resolution synchronous measurement of local temperature in brown adipose tissue, abdomen, and peripherally on the leg enables interrogation of rodent thermoregulation at an unprecedented level of detail.
A leading system for high-resolution metabolic and behavioral rodent phenotyping, the Promethion Core is a highly adaptable and flexible system, capable of simultaneous measurement of a wide range of metrics related to energy balance and behavior. With the core functionality centered around respirometry and measurement of food/water intake, body weight and ambulatory activity patterns, the capabilities of the system can be expanded tremendously. I am experienced in the additional use of climate control cabinets, running wheels and metabolic treadmills, access control doors for restriction of food intake, and add-on external gas analyzers for detecting stable isotopes and methane. In addition, I have established several non-standard modifications such as incorporation of externalized tethers for catheter models, whereby you can add infusion/bolus dosing and collection of blood or urine to the experimental design without compromising the respirometry measurements. Furthermore, I can help with incorporation of implantable device systems such as DSI telemetry or the UID Mouse Matrix system to provide additional physiological measures like body temperature, blood glucose, blood pressure etc., which can promote an even deeper understanding of your experimental model.
Designed with the ability to be used with virtually any cage type, the BioDAQ food and water intake monitoring system offers unparallelled configuration flexibility for measuring food and/or water intake and preference, and the E3 version includes programmable access control modules for caloric- or time-restricted feeding or pair-feeding studies. By combining the BioDAQ E3 with DSI blood glucose telemetry (pictured here), I have developed an experimental model enabling detailed investigation of blood glucose control in response to feeding behavior, dietary composition, and voluntary ingestion of controlled amounts of glucose.
The DVC system represents the next generation of rodent IVC housing where sensors integrated in the housing rack provide continuous, real-time, and non-invasive monitoring of a range of parameters and behaviors of the animals. Designed for scalability across entire animal facilities, the system is capable of tracking all cages in the vivarium and continuously monitor animal activity, bedding conditions, environmental conditions, and food and water availability.
When experimental systems are collecting continuous physiological data from multiple channels in high resolution, the handling, analysis, and interpretation of the recorded data represents a unique challenge. However, with the proper analytical tools for longitudinal and circadian analysis, the scientific benefits of undisturbed, stress-free continuous monitoring of experimental animals in their home environment can hardly be overestimated.
Having worked with numerous different types of continuous systems, I am highly competent in exploiting the tremendous amount of information contained in a continuous data trace, to derive meaningful novel metrics and digital biomarkers which can uncover novel physiological responses in unprecedented detail and accelerate your scientific discoveries.
My experience with complex data analysis and digital biomarkers include:
I’m always excited to connect with like-minded professionals who are looking to advance preclinical in vivo research or need expert guidance on navigating the complexities of advanced in vivo methodologies.
