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Mexiletine has no effect on defibrillation energy requirements in dogs
Abstract:
Many of the antiarrhythmic drugs produce a rise in the ventricular defibrillation threshold (DFT). Although mexiletine has also been reported as the probable cause of a significant elevation of DFT, there has been no previous study; therefore, the effect of mexiletine on DFT was investigated in the present study. The experiments were performed on ten mongrel dogs in the open-chest state using general anesthesia. Mexiletine 1, 2, 4, 6, or 8 mg/kg was administered as the loading dose, followed by the same dose/kg per hour. In these five groups, fibrillation/defibrillation (F/D) trials were performed repeatedly every 10 minutes, until 60 minutes after starting the maintenance dose. F/D trials were also performed at 30, 45, and 60 minutes after the completion of mexiletine infusion. The heart was allowed to fibrillate for a total of 30 seconds. Applying internal paddles to the heart, energies of 2, 3, 5, 7, 10, 20, and 30 J maximum were used. The minimal energy shock that caused defibrillation was defined as the DFT. The mexiletine concentration in each group changed from 0 to 6.11 micrograms/mL, DFT ranged from 2-10 J, and no statistical correlation was found between mexiletine concentration and DFT. We conclude that mexiletine does not induce an increase in DFT in dogs.
Insights
This study found that mexiletine does not increase the ventricular defibrillation threshold (DFT) in dogs. These findings suggest mexiletine may not pose a risk for defibrillation efficacy in canine models.
Area of Science:
- Cardiology
- Pharmacology
- Electrophysiology
Background:
- Antiarrhythmic drugs can elevate the ventricular defibrillation threshold (DFT).
- Mexiletine has been suspected to increase DFT, but prior research was lacking.
Purpose of the Study:
- To investigate the effect of mexiletine on ventricular defibrillation threshold (DFT) in a canine model.
- To determine if mexiletine administration alters the energy required for defibrillation.
Main Methods:
- Experiments were conducted on ten mongrel dogs under general anesthesia in an open-chest state.
- Mexiletine was administered at varying doses (1-8 mg/kg loading and maintenance).
- Fibrillation/defibrillation trials were performed at intervals up to 60 minutes post-infusion, measuring minimal defibrillation energy.
Main Results:
- Mexiletine concentrations ranged from 0 to 6.11 µg/mL.
- Ventricular defibrillation threshold (DFT) ranged from 2-10 Joules across all groups.
- No statistically significant correlation was observed between mexiletine concentration and DFT.
Conclusions:
- Mexiletine administration did not result in an increased ventricular defibrillation threshold (DFT) in the studied canine model.
- These results indicate that mexiletine may not negatively impact defibrillation efficacy in dogs.