Effect of IKr blocker nifekalant on atrial action potential duration after successful internal cardioversion of chronic atrial fibrillation.
BACKGROUND
Chronic atrial fibrillation (AF) is characterized by a marked decrease in the atrial effective refractory period (ERP) and in the ERP adaptation to rate as well as a decrease in the atrial conduction velocity. Little information is available about the ionic mechanisms underlying AF in humans.


METHODS
We studied the effect of IKr blocker nifekalant on the rate-dependent changes in atrial action potential duration in 11 patients after successful internal cardioversion of chronic AF of >2 months duration and in 7 patients without AF. In AF patients, right atrial (RA) monophasic action potential (MAP) was recorded at pacing cycle lengths (CLs) of 800-250 ms before and after administration of nifekalant. In control patients, RAMAP was recorded at CLs of 600 and 350 ms before and after administration of nifekalant.


RESULTS
Nifekalant significantly increased RAMAPD at 90% repolarization (RAMAPD90) at CLs of 800-300 ms in the AF patients. The increase in RAMAPD90 by nifekalant became significantly smaller at shorter CLs (42.5 +/- 12.4 ms at a CL of 600 ms vs 32.8 +/- 14.5 ms at a CL of 350 ms, P < 0.05). Effect of nifekalant on RAPMAPD was attenuated at CL of 600 ms in AF patients in comparison to control patients (increase in RAMAPD in control; 73.0 +/- 36.6 ms vs increase in RAMAPD in AF; 42.5 +/- 12.4 ms, P < 0.05); however, it was similar at a CL of 350 ms between control and AF patients.


CONCLUSIONS
Electrophysiological effects of nifekalant are significantly attenuated in the chronically remodeled human atrium at slower heart rates, but the beneficial effect of RAMAPD prolongation by IKr blocker was well-preserved even at shorter CLs after chronic AF.
Kofune
Tatsuya
T
Division of Cardiovascular Disease, Department of Medicine, Nihon University School of Medicine, Oyaguchi-kami, Itabashi-ku, Tokyo, Japan.
Watanabe
Ichiro
I
Okubo
Kimie
K
Okumura
Yasuo
Y
Masaki
Riko
R
Shindo
Atsushi
A
Saito
Satoshi
S
D000200:Action Potentials / Q000187:drug effects; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000503:physiopathology* / Q000628:therapy*; D002908:Chronic Disease; D004554:Electric Countershock; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000494:pharmacology* / Q000627:therapeutic use; D012032:Refractory Period, Electrophysiological
D000889:Anti-Arrhythmia Agents; D011744:Pyrimidinones; C076259:nifekalant