Related Experiment Videos
Acceleration-induced action potential prolongation and early afterdepolarizations
A Burashnikov1, C Antzelevitch
1Masonic Medical Research Laboratory, Utica, New York 13501, USA.
Journal of Cardiovascular Electrophysiology
|October 24, 1998
Summary
Heart rate acceleration can trigger early afterdepolarizations and action potential prolongation in M cells, potentially leading to Torsades de Pointes (TdP) in long QT syndrome patients.
Area of Science:
- Cardiac Electrophysiology
- Molecular Cardiology
Background:
- Torsades de Pointes (TdP) is linked to heart rate acceleration.
- Investigating cellular mechanisms of acceleration-induced TdP is crucial.
Purpose of the Study:
- To examine the effect of pacing rate acceleration on canine ventricular M cells pretreated with an IKr blocker (E-4031).
- To elucidate the cellular mechanisms underlying acceleration-induced TdP.
Main Methods:
- Utilized standard microelectrode techniques on canine ventricular epicardial, M region, endocardial, and Purkinje fiber preparations.
- Administered E-4031 to induce early afterdepolarizations (EADs) and manipulated pacing rates.
Main Results:
- E-4031 induced EADs in M cells and Purkinje fibers.
- Sudden pacing acceleration significantly increased EAD activity and action potential duration (APD) prolongation in M cells.
- Ryanodine, flunarizine, and low sodium abolished acceleration-induced EADs and APD prolongation.
Conclusions:
- Pacing acceleration can induce EADs and APD prolongation in M cells via intracellular calcium loading.
- Electrogenic Na/Ca exchange current contributes to these changes.
- These findings explain TdP precipitation in long QT syndrome.