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

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.