Nicorandil ameliorates impulse conduction disturbances during ischemia in isolated arterially perfused canine atria.
BACKGROUND
Nicorandil has protective effects on the ischemic atrial myocardium. However, effects of nicorandil on ischemia-induced impulse conduction disturbances are still uncertain.


METHODS
Optical action potentials were recorded from 256 sites of the left atrium in isolated arterially perfused canine atria during the left atrial ischemia. Constant pacing (BCL = 350 ms) from the left superior pulmonary vein (LSPV) and the posterior left atrium (PLA) was performed, and local conduction velocity (CV) was calculated at the LSPV-left atrial (LA) junction and the right inferior PV (RIPV)-LA junction. Impulse conduction failure was elucidated within the optical mapping field during sinus rhythm.


RESULTS
In the control, ischemia slowed the local CV at both regions regardless of the pacing site, and impulse conduction failure occurred within the mapping field during sinus rhythm. Nicorandil suppressed the ischemic conduction slowing at both regions and prevented the conduction failure. Nicorandil also reduced the dispersion of local CV during ischemia. HMR1098, a blocker of cardiac sarcolemmal K(ATP) channels abolished suppression of the ischemic conduction slowing by nicorandil at the RIPV-LA junction but not at the LSPV-LA junction and induced the conduction failure. 5-HD, a blocker of mitochondrial K(ATP) channels also abolished it at both regions and induced the conduction failure. 5-HD abolished the decreased dispersion of local CV by nicorandil, and HMR1098 further increased the dispersion of local CV compared with the control.


CONCLUSIONS
These results indicate that nicorandil suppresses ischemia-induced impulse conduction disturbances by its action on both the mitochondrial and sarcolemmal K(ATP) channels.
Hirose
Masamichi
M
Department of Molecular Pharmacology, Shinshu University School of Medicine, Nagano 390-8621, Japan. mhirose@shinshu-u.ac.jp
Yano
Shiharu
S
Nakada
Tsutomu
T
Horiuchi-Hirose
Miwa
M
Tsujino
Natsuko
N
Yamada
Mitsuhiko
M
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D004285:Dogs; D006325:Heart Atria / Q000187:drug effects / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects* / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D020108:Nicorandil / Q000494:pharmacology / Q000627:therapeutic use*; D010477:Perfusion / Q000379:methods
D020108:Nicorandil