title: Acetylcholine Suppresses Ventricular Arrhythmias and Improves Conduction and Connexin-43 Properties During Myocardial Ischemia in Isolated Rabbit Hearts.
abstract: BACKGROUND
  Acetylcholine (ACh), a vagal efferent neurotransmitter, markedly improves survival in rats with myocardial ischemia (MI) by preventing ischemic loss of gap junction (Gj) and by inducing anti-apoptotic cascades. However, electrophysiological mechanisms of the antiarrhythmic effect of ACh after acute MI are still unclear.
  
  
  METHODS
  Acute MI was induced by ligation of the left anterior descending (LAD) coronary artery in Langendorff-perfused rabbit hearts with (ACh(+):n = 11) or without (ACh(-):n = 12) 10 μmol/L ACh delivered continuously starting at 5 minutes before LAD ligation. Action potentials on the left ventricular (LV) anterior surface (≈2×2 cm) were recorded by optical mapping during pacing from the LV epicardium (BCL = 500 milliseconds). Conduction velocities (CVs) at 256 sites were calculated and the ventricular tachycardia/ventricular fibrillation (VT/VF) susceptibility was also assessed by programmed electrical stimulation before and 30 minutes after MI. The amount and distribution of Gj protein connexin-43 was analyzed by immunoblotting and immunohistochemistry.
  
  
  RESULTS
  Averaged CV in the ischemic border zone (IBZ) was significantly slower in ACh(-) than in ACh(+) (21 ± 7 vs. 34 ± 6 cm/s; P < 0.01). Short-coupled extra stimulus further decreased CV of IBZ in ACh(-) (13 ± 4 cm/s) but did not change that in ACh(+) (34 ± 5 cm/s), leading to a high incidence of conduction block in IBZ in ACh(-) but not in ACh(+) (83% vs. 0%). VT/VF after MI were induced in ACh(-) but suppressed in ACh(+) (10/12 vs. 3/11; P < 0.01). Connexin-43 in the LV anterior wall was significantly reduced after MI in ACh(-) but not in ACh(+).
  
  
  CONCLUSIONS
  ACh may suppress VT/VF by preventing loss of Gj and improving CV in IBZ during acute MI.
authors.affiliation: Division of Arrhythmia and Electrophysiology, Department of Cardiovascular Medicine.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Aiba
authors.affiliation: Division of Arrhythmia and Electrophysiology, Department of Cardiovascular Medicine.
authors.forename: Takashi
authors.initials: T
authors.lastname: Noda
authors.affiliation: Department of Cardiovascular Dynamics, Research Institute, National Cerebral and Cardiovascular Center Suita, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hidaka
authors.affiliation: Department of Cardiovascular Dynamics, Research Institute, National Cerebral and Cardiovascular Center Suita, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Inagaki
authors.affiliation: Department of Cardiovascular Control, Kochi Medical School, Nankoku, Japan.
authors.forename: Rajesh G
authors.initials: RG
authors.lastname: Katare
authors.affiliation: Department of Cardiovascular Control, Kochi Medical School, Nankoku, Japan.
authors.forename: Motonori
authors.initials: M
authors.lastname: Ando
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sunagawa
authors.affiliation: Department of Cardiovascular Control, Kochi Medical School, Nankoku, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Cardiovascular Dynamics, Research Institute, National Cerebral and Cardiovascular Center Suita, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Sugimachi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000200:Action Potentials; D000818:Animals; D018679:Cholinergic Agonists / Q000494:pharmacology*; D018031:Connexin 43 / Q000378:metabolism*; D006329:Heart Conduction System / Q000187:drug effects*; D015151:Immunoblotting; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism; D010477:Perfusion / Q000379:methods; D011817:Rabbits; D017180:Tachycardia, Ventricular / Q000378:metabolism / Q000517:prevention & control*; D014693:Ventricular Fibrillation / Q000378:metabolism / Q000517:prevention & control*; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D018679:Cholinergic Agonists; D018031:Connexin 43; D000109:Acetylcholine
keywords: acetylcholine; conduction; connexin-43; gap junction; ischemia; optical mapping; ventricular arrhythmias