Increased vulnerability to inducible atrial fibrillation caused by partial cellular uncoupling with heptanol.
We hypothesized that partial cellular uncoupling produced by low concentrations of heptanol increases the vulnerability to inducible atrial fibrillation (AF). The epicardial surface of 12 isolated-perfused canine left atria was optically mapped before and after 1-50 microM heptanol infusion. At baseline, no sustained (>30 s) AF could be induced in any of the 12 tissues. However, after 2 microM heptanol infusion, sustained AF was induced in 9 of 12 tissues (P < 0.001). Heptanol >5 microM caused loss of 1:1 capture during rapid pacing, causing no AF to be induced. AF was initiated by conduction block across the fiber leading to reentry, which broke up after one to two rotations into two to four independent wavelets that sustained the AF. Heptanol at 2 microM had no effect on the cellular action potential duration restitution or on the maximal velocity rate over time of the upstroke. The effects of heptanol were reversible. We conclude that partial cellular uncoupling by heptanol without changing atrial active membrane properties promotes wavebreak, reentry, and AF during rapid pacing.
Division of Cardiology, Cedars-Sinai Research Institute, Department of Medicine, University of California of Los Angeles School of Medicine, Los Angeles, California 90048, USA.
Toshihiko
T
Ohara
Zhilin
Z
Qu
Moon-Hyoung
MH
Lee
Keiko
K
Ohara
Chikaya
C
Omichi
William J
WJ
Mandel
Peng-Sheng
PS
Chen
Hrayr S
HS
Karagueuzian
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001281:Atrial Fibrillation / Q000139:chemically induced / Q000503:physiopathology*; D002450:Cell Communication / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology; D019850:Heptanol / Q000494:pharmacology*; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000187:drug effects; D009206:Myocardium / Q000166:cytology*; D010138:Pacemaker, Artificial
D019850:Heptanol