Acetylcholine Suppresses Ventricular Arrhythmias and Improves Conduction and Connexin-43 Properties During Myocardial Ischemia in Isolated Rabbit Hearts.
Acetylcholine Suppresses Ventricular Arrhythmias and Improves Conduction and Connexin-43 Properties During Myocardial Ischemia in Isolated Rabbit Hearts.
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乙酰胆碱可抑制离体兔心脏心肌缺血期间的室性心律失常并改善传导和连接蛋白 43 特性。
DOI：
10.1111/jce.12663
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Sugimachi M.
中科院分区：
文献类型：
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作者：
③Aiba T;Noda T;Hidaka I;Inagaki M;Katare RG;Ando M;Sunagawa K;Sato T;Sugimachi M.
乙酰胆碱（ACh）是一种迷走神经传出神经递质，通过防止间隙连接（Gj）的缺血性丢失和诱导抗凋亡级联反应，显著改善心肌缺血（MI）大鼠的生存率。方法采用Langendorff灌流法，结扎兔冠状动脉左前降支（LAD），在结扎前5 min开始连续给予ACh（ACh（+）：n = 11）或不给予ACh（ACh（-）：n = 12），建立急性MI模型。在从左心室心外膜起搏（BCL = 500毫秒）期间，通过光学标测记录左心室（LV）前表面（2cm ×2 cm）上的动作电位。计算256个部位的传导速度（CV），并在MI前和MI后30分钟通过程序电刺激评估室性心动过速/室颤（VT/VF）易感性。结果ACh（-）组的缺血边缘区（IBZ）平均CV明显低于ACh（+）组（21 ± 7 vs. 34 ± 6 cm/s; P < 0.01）。短耦合额外刺激进一步降低ACh（-）IBZ的CV（13 ± 4 cm/s），但不改变ACh（+）的CV（34 ± 5 cm/s），导致ACh（-）IBZ传导阻滞的发生率较高，但ACh（+）的IBZ传导阻滞的发生率不高（83% vs 0%）。ACh（-）组心肌梗死后VT/VF发生率明显高于ACh（+）组（10/12 vs.3/11; P < 0.01）。结论ACh可能通过抑制Gj的丢失和改善IBZ区的CV来抑制VT/VF。
ACh Prevents Ischemic Loss of Gj and ArrhythmiasIntroductionAcetylcholine (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 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.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.