Interactions between antiarrhythmic drugs and cardiac memory.
OBJECTIVE
Ventricular pacing or arrhythmias can induce cardiac memory (CM). We hypothesized that clinically administered antiarrhythmic drugs alter the expression of CM, and that the repolarization changes characteristic of CM can modulate the effects of antiarrhythmic drugs.


METHODS
We studied conscious, chronically-instrumented dogs paced for two 1-h periods to study the effects of drugs on the evolution of memory (protocol 1) or for 21 days (protocol 2) to observe the effects of steady-state memory on drug actions. Dogs were treated in both settings with quinidine, lidocaine or E4031, in random order, and within therapeutic serum concentration ranges.


RESULTS
Pacing, alone, for 2 h significantly prolonged ERP only near the left ventricular pacing site, whereas pacing alone for 21 days prolonged ERP at all sites (P<0.05). Quinidine and E4031, but not lidocaine, prolonged repolarization and ERP and suppressed evolution of CM in protocol 1. However, quinidine's effect in prolonging repolarization was diminished in both protocols, while its effect in prolonging ERP was diminished in the 21-day protocol only. In contrast, the effects of E4031 were additive to those of CM, prolonging repolarization and ERP in both protocols, while lidocaine showed no changes in effect at all.


CONCLUSIONS
Pacing to induce CM significantly affects ventricular repolarization and refractoriness, and there are interactions between CM, quinidine and E4031. Depending on the specific drug, these interactions have the potential to be anti- or proarrhythmic, and may impact importantly on the clinical efficacy of drugs as well as on electrophysiologic testing of drug actions.
Plotnikov
A N
AN
Center for Molecular Therapeutics, Departments of Pharmacology and Pediatrics, College of Physicians and Surgeons of Columbia University, New York, NY, USA
Shvilkin
A
A
Xiong
W
W
de Groot
J R
JR
Rosenshtraukh
L
L
Feinmark
S
S
Gainullin
R
R
Danilo
P
P
Rosen
M R
MR
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects*; D004594:Electrophysiology; D005246:Feedback / Q000187:drug effects; D008012:Lidocaine / Q000097:blood / Q000494:pharmacology; D010880:Piperidines / Q000097:blood / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D011725:Pyridines / Q000097:blood / Q000494:pharmacology; D011802:Quinidine / Q000097:blood / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D015221:Potassium Channels; D011725:Pyridines; C063968:E 4031; D008012:Lidocaine; D011802:Quinidine