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Electrophysiologic effects of mexiletine in children
Insights
Mexiletine administration in children with heart disease did not significantly alter cardiac refractory periods or conduction intervals. However, it consistently increased heart rate without reported side effects, unlike in adults.
Area of Science:
- Cardiology
- Pharmacology
- Pediatric Electrophysiology
Background:
- Mexiletine is an antiarrhythmic medication.
- Its effects on cardiac electrophysiology, particularly in pediatric populations, require further elucidation.
Purpose of the Study:
- To investigate the impact of intravenous mexiletine on atrial and atrioventricular (AV) node refractory periods in children with heart disease.
- To assess mexiletine's effects on cardiac conduction intervals and heart rate in this cohort.
Main Methods:
- Ten children with heart disease received intravenous mexiletine (3 mg/Kg bolus, then 1 mg/Kg/hr infusion).
- His bundle recordings and atrial pacing with extrastimulus technique were used.
- Measurements included sinus cycle length, AH and HV intervals, and functional/effective refractory periods of the atrium and AV node.
Main Results:
- Mexiletine significantly reduced sinus cycle length (heart rate increased).
- No significant changes were observed in atrial or AV node refractory periods, or in AH and HV intervals.
- These findings contrast with adult studies where sinus cycle length is unaffected.
Conclusions:
- Intravenous mexiletine in children with heart disease primarily affects heart rate, increasing it without significantly altering cardiac refractory periods or conduction.
- The observed lack of side effects in children differs from adult experiences with parenteral mexiletine, suggesting a potentially better pediatric tolerability profile.
Abstract:
The effects of intravenous administration of mexiletine on the refractory periods of the atrium and atrioventricular (AV) node were studied using His bundle recordings and the extrastimulus technique with atrial pacing. The drug was administered to 10 children with heart disease in an intravenous bolus dose of 3 mg/Kg, injected over a 5-min period, followed by an infusion of 1 mg/Kg/hr of mexiletine, achieving a mean therapeutic plasma concentration of 0.762 +/- 0.270 microgram/ml. The AH and HV intervals, the resting sinus cycle length, and the functional and effective refractory periods of the atrium and AV node were measured before and 5 min after initiation of the mexiletine infusion. The sinus cycle length was reduced significantly. However, neither the refractory periods nor the AH and HV intervals changed in a significant manner. Except for the heart rate, these results are similar to those reported in adults without conduction disturbances. In adults, mexiletine did not affect the sinus cycle length. However, in children, it consistently increased the heart rate. The lack of side effects in children is in contrast to adults, who usually suffer from gastrointestinal and neurologic symptoms upon receiving comparable doses parenterally.