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

Samenvatting

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.

Materialen

Lijst van materialen gebruikt in dit artikel

Naam	Bedrijf	Catalogusnummer	Opmerkingen
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