Monitoring haemodynamic changes in rodent models to better inform safety pharmacology: Novel insights from in vivo studies and waveform analysis

Van Daele, Marieke; Cooper, Samantha L.; Pannucci, Patrizia; Wragg, Edward S.; March, Julie; de Jong, Iwan; Woolard, Jeanette

Abstract

Animal models are essential for assessing cardiovascular responses to novel therapeutics. Cardiovascular safety liabilities represent a leading cause of drug attrition and better preclinical measurements are essential to predict drug-related toxicities. Presently, radiotelemetric approaches recording blood pressure are routinely used in preclinical in vivo haemodynamic assessments, providing valuable information on therapy-associated cardiovascular effects. Nonetheless, this technique is chiefly limited to the monitoring of blood pressure and heart rate alone. Alongside these measurements,
Doppler flowmetry can provide additional information on the vasculature by simultaneously measuring changes in blood flow in multiple different regional vascular beds. However, due to the time-consuming and expensive nature of this approach, it is not widely used in the industry. Currently, analysis of waveform data obtained from telemetry and Doppler flowmetry typically examines averages or peak values of waveforms. Subtle changes in the morphology and variability of physiological waveforms have previously been shown to be early markers of toxicity and pathology. Therefore, a
detailed analysis of pressure and flowmetry waveforms could enhance the understanding of toxicological mechanisms and
the ability to translate these preclinical observations to clinical outcomes. In this review, we give an overview of the different approaches to monitor the effects of drugs on cardiovascular parameters (particularly regional blood flow, heart rate and blood pressure) and suggest that further development of waveform analysis could enhance our understanding of safety pharmacology, providing valuable information without increasing the number of in vivo studies needed.

Citation

Van Daele, M., Cooper, S. L., Pannucci, P., Wragg, E. S., March, J., de Jong, I., & Woolard, J. (2022). Monitoring haemodynamic changes in rodent models to better inform safety pharmacology: Novel insights from in vivo studies and waveform analysis. JRSM Cardiovascular Disease, 11, 1-9. https://doi.org/10.1177/20480040221092893

• Journal Article Type: Article
• Acceptance Date: Mar 22, 2022
• Online Publication Date: May 23, 2022
• Publication Date: Jan 1, 2022
• Deposit Date: Apr 29, 2022
• Publicly Available Date: Apr 29, 2022
• Journal: JRSM Cardiovascular Diseases
• Electronic ISSN: 2048-0040
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Pages: 1-9
• DOI: https://doi.org/10.1177/20480040221092893
• Public URL: https://nottingham-repository.worktribe.com/output/7838591
• Publisher URL: https://journals.sagepub.com/doi/full/10.1177/20480040221092893