Effect of Renal Denervation on Neurohumoral Activation Triggering Atrial Fibrillation in Obstructive Sleep Apnea

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 β-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.