Patterson Eugene, Yu Xichun, Huang Shijun, Garrett Marion, Kem David C
University of Oklahoma Health Sciences Center, OU Medical Center, Oklahoma City, Oklahoma 73104, USA.
J Cardiovasc Electrophysiol. 2006 Jul;17(7):763-70. doi: 10.1111/j.1540-8167.2006.00507.x.
Rapid arrhythmia originating within pulmonary veins (PVs) precipitates atrial fibrillation (AF) in man. To determine a possible basis for an increased incidence of AF observed peri-myocardial infarction in man, we compared AF induction in vivo and triggered arrhythmia formation within isolated PVs in vitro in normal dogs and dogs studied 24 hours postcoronary artery ligation.
The incidence of AF initiated by atrial premature stimuli was increased in dogs postcoronary artery ligation (6/9) versus normal (2/12) (P = 0.03). In isolated PVs from normal hearts, pause-dependent early afterdepolarizations (EADs) were enhanced by catecholamines. Rapid arrhythmia (1,182 +/- 213 beats/min) was triggered during isoproterenol/norepinephrine (32 nM) + acetylcholine (100 nM) (N = 16/23) using the same pacing pauses eliciting EADs. Rapid arrhythmia (802 +/- 161 beats/min) was also triggered by local autonomic nerve stimulation (ANS; N = 18/23). Despite equivalent pause-dependent afterdepolarization formation in PVs from infarcted hearts, a rightward 45-fold and 28-fold shift in the dose-response curve for afterdepolarization enhancement was observed for isoproterenol and norepinephrine, respectively (P < 0.02). ANS (N = 1/19) and isoproterenol/norepinephrine (32 nM) + acetylcholine (100 nM) (N = 0/9 and 0/12, respectively) (P = 0.0001) failed to elicit arrhythmia formation. Beta-adrenergic receptor desensitization was associated with a 2.5-fold increase in PV beta-adrenergic receptor kinase (ARK).
The data demonstrate decreased susceptibility of isolated canine PVs for arrhythmia triggered by local ANS, or pacing pauses in the presence of a catecholamine + acetylcholine, postmyocardial infarction, despite a greater susceptibility of the intact heart to AF. The decreased arrhythmia susceptibility was observed coincident with an increase in beta-ARK and a decreased responsiveness to beta-adrenergic receptor agonists.
起源于肺静脉（PVs）的快速心律失常可诱发人类房颤（AF）。为了确定人类心肌梗死周围观察到的房颤发生率增加的可能原因，我们比较了正常犬和冠状动脉结扎24小时后犬的体内房颤诱发情况以及体外分离PVs中触发心律失常的形成情况。
冠状动脉结扎后的犬（6/9）由房性早搏刺激引发房颤的发生率高于正常犬（2/12）（P = 0.03）。在正常心脏分离的PVs中，儿茶酚胺可增强依赖于长间歇的早期后除极（EADs）。使用引发EADs的相同起搏长间歇，在异丙肾上腺素/去甲肾上腺素（32 nM）+乙酰胆碱（100 nM）作用期间触发了快速心律失常（1,182±213次/分钟）（N = 16/23）。局部自主神经刺激（ANS）也触发了快速心律失常（802±161次/分钟）（N = 18/23）。尽管梗死心脏的PVs中依赖于长间歇的后除极形成相当，但异丙肾上腺素和去甲肾上腺素的后除极增强剂量反应曲线分别向右移位45倍和28倍（P < 0.02）。ANS（N = 1/19）以及异丙肾上腺素/去甲肾上腺素（32 nM）+乙酰胆碱（100 nM）（分别为N = 0/9和0/12）（P = 0.0001）未能诱发心律失常形成。β-肾上腺素能受体脱敏与PVs中β-肾上腺素能受体激酶（ARK）增加2.5倍相关。
数据表明，尽管完整心脏对房颤更易感，但心肌梗死后，分离的犬PVs对局部ANS或儿茶酚胺+乙酰胆碱存在时的起搏长间歇触发的心律失常的易感性降低。心律失常易感性降低与β-ARK增加以及对β-肾上腺素能受体激动剂的反应性降低同时出现。
