Acetylcholine Suppresses Ventricular Arrhythmias and Improves Conduction and Connexin-43 Properties During Myocardial Ischemia in Isolated Rabbit Hearts

作者：Aiba Takeshi^*; Noda Takashi; Hidaka Ichiro; Inagaki Masashi; Katare Rajesh G; Ando Motonori; Sunagawa Kenji; Sato Takayuki; Sugimachi Masaru

来源：Journal of Cardiovascular Electrophysiology, 2015, 26(6): 678-685.

DOI：10.1111/jce.12663

• acetylcholine
• conduction
• connexin-43
• gap junction
• ischemia
• optical mapping
• ventricular arrhythmias

ACh Prevents Ischemic Loss of Gj and Arrhythmias
IntroductionAcetylcholine (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.
MethodsAcute 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 mol/L ACh delivered continuously starting at 5 minutes before LAD ligation. Action potentials on the left ventricular (LV) anterior surface (approximate to 2x2 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.
ResultsAveraged 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(+).
ConclusionACh may suppress VT/VF by preventing loss of Gj and improving CV in IBZ during acute MI.

• 出版日期2015-6