Effect of Renal Denervation on Neurohumoral Activation Triggering Atrial Fibrillation in Obstructive Sleep Apnea
Effect of Renal Denervation on Neurohumoral Activation Triggering Atrial Fibrillation in Obstructive Sleep Apnea
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DOI：
10.1161/hypertensionaha.113.01728
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发表时间：
2013-10-01
期刊：
影响因子：
8.3
通讯作者：
Boehm, Michael
中科院分区：
文献类型：
--
作者：
Linz, Dominik;Hohl, Mathias;Boehm, Michael
阻塞性睡眠呼吸暂停的特征是上呼吸道的反复塌陷、胸压负期和间歇性缺氧，刺激自主神经系统。阻塞性睡眠呼吸暂停期间交感神经驱动增加导致呼吸暂停后血压升高和神经体液激活，可能参与永久性房颤（AF）的发生和进展。在模拟阻塞性睡眠呼吸暂停的猪模型中，我们研究了持续4小时的重复阻塞性呼吸事件对自发性AF发作、呼吸暂停后血压升高和神经体液激活的影响。此外，进行肾交感神经去支配以研究交感神经系统的影响。重复性阻塞性呼吸事件导致明显的呼吸暂停后血压升高，自发性心房搏动触发的自发性AF发作持续时间延长，血浆肾素活性和醛固酮浓度升高。这与烟酰胺腺嘌呤二核苷酸磷酸氧化酶活性增加、抗氧化能力降低和结缔组织生长因子（一种氧化还原敏感的纤维化介质）表达升高有关。去肾交感神经可抑制呼吸暂停后血压升高，降低血浆肾素活性和醛固酮浓度。与血管紧张素受体和β-肾上腺素受体的联合药物阻滞剂相比，自发性AF的发生率和持续时间减少。增加心房氧化应激，连同激活的促纤维化途径和间歇性缺氧，肾交感神经去神经后没有减弱。反复的阻塞性呼吸事件触发自发性房颤，增加心房氧化应激，激活心房内的促纤维化通路。去肾交感神经可通过减少交感神经驱动和循环中的肾素-血管紧张素系统的成分来减少自发性房颤和呼吸暂停后血压升高。然而，心房氧化应激的产生并未受到调节。
Obstructive sleep apnea is characterized by repetitive collapses of the upper airway, negative thoracic pressure periods, and intermittent hypoxia, stimulating the autonomic nervous system. The increased sympathetic drive during obstructive sleep apnea results in postapneic blood pressure rises and neurohumoral activation potentially involved in the initiation and progression to permanent atrial fibrillation (AF). In a pig model mimicking obstructive sleep apnea, we studied the effects of repetitive obstructive respiratory events for 4 hours on the occurrence of spontaneous AF episodes, postapneic blood pressure rises, and neurohumoral activation. In addition, renal sympathetic denervation was performed to investigate the impact of the sympathetic nervous system. Repetitive obstructive respiratory events caused pronounced postapneic blood pressure rises, prolonged duration of spontaneous AF episodes triggered by spontaneous atrial beats, and increased plasma renin activity and aldosterone concentrations. This was associated with increased nicotinamide adenine dinucleotide phosphate-oxidase activity, reduced antioxidative capacity, and elevated expression of connective tissue growth factor, a redox-sensitive mediator of fibrosis. Renal sympathetic denervation inhibited postapneic blood pressure rises and decreased plasma renin activity and aldosterone concentrations. The occurrence and duration of spontaneous AF were reduced comparable with a combined pharmacological blockade of angiotensin receptor and beta-adrenoceptor. Increased atrial oxidative stress, together with the activation of profibrotic pathways and intermittent hypoxia, was not attenuated after renal sympathetic denervation. Repetitive obstructive respiratory events triggered spontaneous AF, increased atrial oxidative stress, and activated profibrotic pathways in the atrium. Renal sympathetic denervation reduced spontaneous AF and postapneic blood pressure rises by combined reduction of sympathetic drive and components of the circulating renin-angiotensin system. However, the generation of atrial oxidative stress was not modulated.