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Continuous, Automated Breathing Rate and Body Motion Monitoring of Rats With Paraquat-Induced Progressive Lung
Szczepan W Baran1, Ayan Das Gupta2, Maria A Lim3
1Emerging Technologies, Laboratory Animal Services, Scientific Operations, Novartis Institutes for BioMedical Research (NIBR), Inc., Cambridge, MA, United States.
Frontiers in Physiology
|November 12, 2020
Summary
Continuous monitoring of animal breathing rate and body motion offers a more detailed view of lung injury progression and drug efficacy in preclinical studies. This technology complements standard methods for enhanced safety and pharmacology research.
Area of Science:
- Pharmacology and Toxicology
- Animal Models
- Respiratory Physiology
Background:
- Standard in-life measurements in preclinical research can lack granularity for detecting subtle physiological changes.
- Respiratory response and animal activity are critical endpoints in drug pharmacology and safety assessments.
- Paraquat (PQ) toxicity is a well-established rodent model for studying lung injury.
Purpose of the Study:
- To evaluate the utility of continuous, direct monitoring of breathing rate and body motion in home-caged animals.
- To assess if this technology can provide more granular detection of lung injury onset and severity.
- To determine if the technology can complement standard measurements in drug pharmacology and safety research.
Main Methods:
- Utilized the Vum Digital Smart House for continuous monitoring of breathing rate and body motion in rats.
- Administered paraquat (PQ) to induce lung injury and assessed the effects on monitored parameters.
- Investigated the response to a potential ameliorative test article, bardoxolone.
- Correlated continuous monitoring data with standard clinical pathology and terminal pathology measurements.
Main Results:
- Paraquat administration significantly elevated breathing rate and reduced body motion in rats throughout the study.
- Time course differences in response to bardoxolone were readily detected.
- Continuous monitoring data aligned with and informed on interval changes in clinical pathology.
- Breathing rates correlated with terminal pathology measurements, including normalized lung weights and histological damage.
Conclusions:
- Continuously measured breathing rate and body motion serve as physiologically relevant readouts for assessing lung injury progression.
- This technology offers a more complete assessment than standard in-life measurements over the full study period.
- The findings demonstrate the potential of this technology to enhance respiratory injury animal models and drug response evaluation.
