British Heart Foundation Glasgow Cardiovascular Research Centre, Division of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK.
Naunyn Schmiedebergs Arch Pharmacol. 2010 Mar;381(3):235-49. doi: 10.1007/s00210-009-0474-0. Epub 2009 Dec 4.
Atrial fibrillation (AF) is the most common cardiac arrhythmia, and it causes substantial mortality. The autonomic nervous system, and particularly the adrenergic/cholinergic balance, has a profound influence on the occurrence of AF. Adrenergic stimulation from catecholamines can cause AF in patients. In human atrium, catecholamines can affect each of the electrophysiological mechanisms of AF initiation and/or maintenance. Catecholamines may produce membrane potential oscillations characteristic of afterdepolarisations, by increasing Ca(2+) current, Ca(2+) and consequent Na(+)-Ca(2+) exchange, and may also enhance automaticity. Catecholamines might affect reentry, by altering excitability or conduction, rather than action potential terminal repolarisation or refractory period. However, which arrhythmia mechanisms predominate is unclear, and likely depends on cardiac pathology and adrenergic tone. Heart failure (HF), a major cause of AF, causes adrenergic activation and adaptational changes, remodelling, of atrial electrophysiology, Ca(2+) homeostasis, and adrenergic responses. Chronic AF also remodels these, but differently to HF. Myocardial infarction and AF cause neural remodelling that also may promote AF. beta-Adrenoceptor antagonists (beta-blockers) are used in the treatment of AF, mainly to control the ventricular rate, by slowing atrioventricular conduction. beta-Blockers also reduce the incidence of AF, particularly in HF or after cardiac surgery, when adrenergic tone is high. Furthermore, the chronic treatment of patients with beta-blockers remodels the atria, with a potentially antiarrhythmic increase in the refractory period. Therefore, the suppression of AF by beta-blocker treatment may involve an attenuation of arrhythmic activity that is caused by increased Ca(2+), coupled with effects of adaptation to the treatment. An improved understanding of the involvement of the adrenergic system and its control in basic mechanisms of AF under differing cardiac pathologies might lead to better treatments.
心房颤动(AF)是最常见的心律失常,它会导致大量死亡。自主神经系统,特别是肾上腺素能/胆碱能平衡,对 AF 的发生有深远的影响。儿茶酚胺的肾上腺素能刺激可导致患者发生 AF。在人类心房中,儿茶酚胺可通过增加 Ca(2+)电流、[Ca(2+)]i 和随后的 Na(+)-Ca(2+)交换来影响 AF 起始和/或维持的每一个电生理机制。儿茶酚胺可能会产生特征性的后除极膜电位振荡,从而增加自动性。儿茶酚胺可能会通过改变兴奋性或传导,而不是动作电位终末复极或不应期来影响折返,而不是动作电位终末复极或不应期。然而,哪种心律失常机制占主导地位尚不清楚,而且可能取决于心脏病理学和肾上腺素能张力。心力衰竭(HF)是 AF 的主要原因,它会导致肾上腺素能激活和适应性改变,改变心房电生理、Ca(2+)稳态和肾上腺素能反应的重塑。慢性 AF 也会对此进行重塑,但与 HF 不同。心肌梗死和 AF 导致神经重塑,也可能促进 AF。β-肾上腺素能受体拮抗剂(β-受体阻滞剂)用于治疗 AF,主要通过减慢房室传导来控制心室率。β-受体阻滞剂还可降低 AF 的发生率,特别是在 HF 或心脏手术后,此时肾上腺素能张力较高。此外,β-受体阻滞剂对患者的慢性治疗会重塑心房,使不应期潜在地增加,从而具有抗心律失常作用。因此,β-受体阻滞剂治疗对 AF 的抑制可能涉及到通过抑制增加的 [Ca(2+)]i 引起的心律失常活动,同时还可能与治疗的适应作用有关。更好地了解在不同心脏病理条件下 AF 的基本机制中涉及的肾上腺素能系统及其控制,可能会导致更好的治疗方法。