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Interactions between antiarrhythmic drugs and cardiac memory.
A N Plotnikov1, A Shvilkin, W Xiong
1Center for Molecular Therapeutics, Departments of Pharmacology and Pediatrics, College of Physicians and Surgeons of Columbia University, New York, NY, USA
Cardiovascular Research
|May 4, 2001
Summary
Cardiac memory (CM) induced by pacing affects drug actions. Quinidine and E4031 interact with CM, altering repolarization and refractoriness, potentially impacting antiarrhythmic drug efficacy and proarrhythmic risk.
Area of Science:
- Cardiovascular Physiology
- Electrophysiology
- Pharmacology
Background:
- Cardiac memory (CM) is induced by ventricular pacing or arrhythmias.
- CM involves changes in ventricular repolarization and refractoriness.
- Antiarrhythmic drugs are used to treat arrhythmias.
Purpose of the Study:
- To investigate how antiarrhythmic drugs alter CM.
- To determine if CM modulates the effects of antiarrhythmic drugs.
- To examine the interactions between CM and specific drugs (quinidine, lidocaine, E4031).
Main Methods:
- Conscious dogs were instrumented and paced to induce CM.
- Two protocols were used: short-term pacing (1-h periods) and long-term pacing (21 days).
- Dogs received quinidine, lidocaine, or E4031 within therapeutic serum concentrations.
Main Results:
- Long-term pacing prolonged ventricular effective refractory period (ERP) globally.
- Quinidine and E4031 suppressed CM evolution and prolonged repolarization/ERP.
- E4031's effects were additive to CM; lidocaine's effects were unchanged.
Conclusions:
- CM significantly alters ventricular repolarization and refractoriness.
- Interactions between CM and drugs like quinidine and E4031 exist.
- These interactions can be anti- or proarrhythmic, influencing drug efficacy and testing.