Evaluating a non-invasive telemetry jacket as an alternative to the reference methods for cardio-respiratory safety pharmacological testing in rats

Abstract

The gold standard methods used to assess cardiorespiratory system in rats, whether telemetry implants or whole-body plethysmography (WBP), have their shortcomings. One method requires surgery, while the other involves the isolation of rats. In a 3Rs approach, alternatives such as the use of non-invasive telemetry jackets, allowing simultaneous cardiorespiratory assessment, without hemodynamic parameters evaluation have been considered. No peer-reviewed publication to date has investigated the concordance between cardiorespiratory parameters recorded simultaneously via the jackets and the reference methods, following the administration of a pharmacological compound. Goal: to test and potentially validate the telemetry jackets by comparing data generated using this device with those obtained using gold standard methods at the same time, in the same animal, in an integrative interpretation approach. We compared cardiac (heart rate (HR)) and respiratory (respiratory rate (RR), minute ventilation (MV), tidal volume (TV)) parameters recorded via the invasive (DSI implant), non-invasive (Jacket DECRO) telemetry systems, and via the WBP (Buxco + Notocord HEM), simultaneously in the same male rats (n = 8rats/ pharmacological compound in a cross-over design). The recording lasted 7 h after the per-os administration of vehicle or pharmacological reference compounds tested (Ivabradine or Theophylline) at 3 doses. A generalized linear model was used to assess the effects of the pharmacological compounds. The Bland-Altman method was used to study the agreement between the jackets and the two reference methods. The jackets and reference methods both captured the expected pharmacological effects. For Ivabradine, a significant dose-dependent decrease in HR was observed, while no changes were noted in respiratory variables. Theophylline induced a dose-dependent increase in heart rate and RR. No significant change on TV and MV was noticed with the WBP, whereas a significant increase was shown with the jackets. Bland-Altman analysis revealed an increasing discrepancy in high TV, RR and MV values between the two devices under the experimental conditions of the studies. Jackets can be used as an alternative to implanted telemetry for recording HR without hemodynamic parameters. Although the two respiratory methods detect pharmacological effects, further investigation is needed to determine what is the current state of the respiratory parameters.