A New Telemetry-Based System for Assessing Cardiovascular Function in Group-Housed Large Animals. Taking the 3Rs to a New Level With the Evaluation of Remote Measurement via Cloud Data Transmission

J Pharmacol Toxicol Methods. Sep-Oct 2018;93:90-97. doi: 10.1016/j.vascn.2018.03.006. Epub 2018 Mar 26.

Abstract

Introduction: A newly developed total implant telemetry system for cardiovascular (CV), electrophysiological and body temperature measurement was evaluated. A cloud-based transmission of the physiological signals allowed an assessment of the quality of the physiological signals despite the physical separation between the instrumented animals and the evaluating home laboratory. The new system is intended to be used for safety pharmacological evaluations of drug candidates in various species.

Methods: Two female minipigs, 6 Labrador-mixed breed dogs and 4 female Cynomolgus monkeys were instrumented with a newly developed total implant system (TSE SYSTEMS). The implants feature a microprocessor, internal memory (1 GB), 2 solid state pressure-tipped catheters, amplifiers and a radio transmitter. Sampling rates for each measurement can be selected within a range between 0.1 and 1 kHz. Biological signals are selected in a programmable fashion on a session-by-session basis according to a user-defined protocol. The pressure sensors are at the tip of an electrical lead having a length customized to each species. Core temperature measurement and activity monitoring (3D accelerometer) are included in the system. Digital transmission range using a single antenna is 5 m with up to 16 animals held together and monitored simultaneously. The range can be expanded with more antennas in an array coupled to a single receiver. The antenna/receiver station consists of a single USB powered mobile unit connected to a PC or laptop. The battery life provides 110 days of continuous recording. The dogs and minipigs were instrumented and monitored in Germany. A novel cloud-based data transmission system was developed to monitor the physiological signals in real-time from the Cynomolgus monkeys, still kept in Mauritius, from the data evaluation laboratory in Germany. After recovery from the surgical implantation, aortic pressure (AP), left ventricular pressure (LVP), ECG and body temperature were recorded for 24 hr monitoring sessions in all animals. Additionally, moxifloxacin (10, 30 and 100 mg/kg) was tested in the dog model using a modified Latin square cross-over study design.

Results: The implant was well tolerated and the animals recovered rapidly from the implantation procedure. Excellent signal quality was obtained and stable hemodynamic and electrophysiological parameters could be measured, with little signal artefact or drop-out, over 24 h in each species. After oral dosing of moxifloxacin to the dogs, a substantial, dose-dependent increase in the QT-interval duration could be shown, as anticipated for this agent. Cloud-based data acquisition from the animals in Mauritius and the data evaluation lab in Germany worked well.

Conclusion: This new CV telemetry system provides a novel alternative to fluid-filled catheter telemetry systems and the coupling to a cloud-based data transmission allows for flexibility in the location of the instrumented animals and data acquisition and the location of the site for data analysis. For the first time it is technically feasible to conduct a CV safety pharmacology study in Cynomolgus monkeys without having to ship them long distances to the home laboratory.

Keywords: Blood pressure; Cardiovascular; Cloud data; Conscious dogs; Conscious minipig; Conscious non-human primate; ECG; Methods; Safety pharmacology; Stellar implants; TSE SYSTEMS; Telemetry.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Blood Pressure / drug effects
  • Blood Pressure / physiology*
  • Body Temperature / drug effects
  • Body Temperature / physiology*
  • Cloud Computing* / trends
  • Cross-Over Studies
  • Dogs
  • Female
  • Heart Rate / drug effects
  • Heart Rate / physiology*
  • Macaca fascicularis
  • Male
  • Moxifloxacin / pharmacology
  • Remote Sensing Technology / instrumentation
  • Remote Sensing Technology / methods*
  • Remote Sensing Technology / trends
  • Swine
  • Swine, Miniature
  • Telemetry / instrumentation
  • Telemetry / methods*
  • Telemetry / trends

Substances

  • Anti-Bacterial Agents
  • Moxifloxacin