Multisystem Monitoring in Rabbit Model: A Method to Assess Neuro-Cardiac and Respiratory Parameters to Study the Oral Drug-induced Triggers for Arrhythmia and Seizures

Published: April 30, 2023

Abstract

Source: Bosinski, C., et al. Multi-system Monitoring for Identification of Seizures, Arrhythmias and Apnea in Conscious Restrained Rabbits. J. Vis. Exp. (2021).

In this video, we describe simultaneous recording of video, EEG, ECG and respiratory cues in a rabbit model in response to orally administered drug to understand the sequence of events leading to seizure. The model can be used for testing potential drugs for their neuro-cardiac safety.

Protocol

All procedures involving animal models have been reviewed by the local institutional animal care committee and the JoVE veterinary review board.

1. Oral administration of medications

  1. As many drugs are taken orally, prepare oral compounds by mixing with food-grade apple sauce. Mix 0.3 mg/kg of E-4031 in 3 mL of apple sauce and load into a 3 mL oral/irrigation syringe without a needle.
    NOTE: Several medications can be administered in this fashion including, test compounds, drugs that are known to alter the QT duration (moxifloxacin or E-4031), and a negative control or vehicle. Some drugs are not available in an intravenous formulation. In addition, many medications are prescribed in an oral formulation and therefore an intravenous administration may have less clinical relevance.
  2. Lift the upper lips and slide the tip of the oral syringe into the side of the rabbit's mouth, which is unobstructed by the rabbit's teeth, and inject all of the medication and apple sauce into the rabbit's mouth.
  3. Continue the video-EEG-ECG recording for 2 h and then return the animal to its home cage for routine care.
  4. On the experimental day 2 and 3, connect the rabbit to the video-EEG-ECG, record 10-20 min of baseline, then inject the same medication and record for 2 h.
  5. After 1 week of washout, perform 10-20 min of baseline, and then give each rabbit a single dose of placebo for 3 consecutive days and record for 2 h.
    NOTE: Administration of oral medications may be designed as a crossover study, in which the placebo is given during week 1 and the medication in week 2.

Divulgations

The authors have nothing to disclose.

Materials

Apple Sauce Kirkland 897971 Vehicle for oral medications
Computer Dell Optiplex 5040 Acquisition computer
E-4031 Tocris 1808 Agent known to prolong the QT interval
ECG Electrode RhythmLink RLSND116-2.5 13mm 35-degree bent (0.4 mm diameter) subdermal pin electrodes
EEG Electrode RhythmLink RLSP513 5-twist 13mm straight (0.4mm diameter) subdermal pin electrodes
EEGLAB (2020) Swartz Center for Computational Neuroscience Open Access Can perform spectral analysis of EEG
Ethernet-to-ethernet adapter Linksys USB3G16 Adapter for connecting the camera to the computer
LabChart Pro (2019, Version 8.1.16) ADInstruments N/A ECG Analysis
MATLAB (R2019b, Update 5) MathWorks N/A Required to run EEGLAB
Microphone Sony Stereo ECM-D570P Recording of audible manifestions of seizures
Natus NeuroWorks Natus LC101-8 Acquisition and review software
Plastic wire organizer / bundler 12Vwire.com LM-12-100-BLK Bundle wires to cut down on noise
PVC pipe Generic N/A Prevents small rabbits from kicking their hind legs and causing spinal injury
Quantum Amplifier Natus 13926 Amplifier / digitizer
Quantum HeadBox Amplifier Natus 22134 64-pin breakout box
Rabbit Restrainer Plas-Labs 501-TC Various size rabbit restrainers are available. 6" x 18" x 6" in this study.
Rubber pad (booster) Generic N/A Raises small rabbits up in the restrainer to prevent neck compression
SpO2 ear clip NONIN 61000 PureSAT/SpO2
SpO2 sensor adapter NONIN 13931 XPOD PureSAT/SpO2
SRG-X120 1080p PTZ Camera with HDMI, IP & 3G-SDI Output Sony SRG-X120 Impela Camera

Tags

Play Video

Citer Cet Article
Multisystem Monitoring in Rabbit Model: A Method to Assess Neuro-Cardiac and Respiratory Parameters to Study the Oral Drug-induced Triggers for Arrhythmia and Seizures. J. Vis. Exp. (Pending Publication), e20825, doi: (2023).

View Video