Muscle Sympathetic Nerve Activity During Wakefulness in Heart Failure Patients With and Without Sleep Apnea

Abstract

Abstract-Sympathetic activation and sleep apnea are present in most patients with symptomatic systolic heart failure (HF). Acutely, obstructive and central apneas increase muscle sympathetic activity (MSNA) during sleep by eliciting recurrent hypoxia, hypercapnia, and arousal. In obstructive sleep apnea patients with normal systolic function, this increase persists after waking. Whether coexisting sleep apnea augments daytime MSNA in HF is unknown. We tested the hypothesis that its presence exerts additive effects on MSNA during wakefulness. Overnight sleep studies and morning MSNA recordings were performed on 60 subjects with ejection fraction Ͻ45%. Of these, 43 had an apnea-hypopnea index Ն15 per hour. Subjects with and subjects without sleep apnea were similar for age, ejection fraction, HF etiology, body mass index, blood pressure, and heart rate.

Sleep Apnea and Cardiovascular Disease

“…In patients with heart failure, the coexistence of OSA may be associated with higher sympathetic nerve activity and higher systolic BP during wakefulness, despite more intense antihypertensive therapy. 177 Responses to cytokines, catecholamines, endothelin, and other growth factors produced in OSA also may contribute to ventricular hypertrophy independently of hypertension. Indeed, there is evidence to suggest that OSA is associated with altered cardiac structure and function 121,123,178,179 and that some of these changes may be reversible with effective CPAP treatment.…”

“…343 Urine and plasma norepinephrine levels and muscle sympathetic nerve traffic during wakefulness are greater in heart failure patients with CSA compared with those without CSA. 177,344 However, it has been proposed that heightened sympathetic drive in heart failure patients with CSA may simply be a consequence of more severe heart failure rather than a direct consequence of CSA. 345 The role of inflammatory and other mechanisms in CSA remains unclear, in contrast to OSA, in which hypoxemia is usually more severe.…”

Theophylline Therapy for Cheyne-Stokes Respiration During Sleep in a 41-Year-Old Man With Refractory Arterial Hypertension

“…A major effect of sleep apnea on the cardiovascular system is sympathetic excitation. 10 Since we had previously sought to alleviate effects of neurohormonal activation in this patient (two b -blockers, angiotensin-converting enzyme inhibitor, and angiotensin receptor blocker), we then gave priority to eliminating CSR during sleep. There are peripheral and central mechanisms of theophylline actions that may result eventually in BP lower ing, including endothelium-dependent and -independent vasorelaxation, 11 , 12 a diuretic effect, and central apnea elimination via adenosine antagonism resulting in attenuation of hypoxemias and hypercapnias.…”

830 Heart failure and sleep disordered breathing

“…The ability of the failing left ventricle to cope with enhanced preload is further impaired by the increased transmural pressure during episodes of negative intrathoracic pressure, which in turn increases the afterload. Apnea and hypopnea activate the sympathetic nervous system, and levels of circulating catecholamines and muscle sympathetic nervous activity are higher in those with SDB and HF than HF without SDB 2,8,18) . These factors accompanied with inflammatory mediators cause hypertension, arrhythmia, coronary arterial disease, myocardial dysfunction and HF 4) .…”

“…In normal physiology, minute ventilation during sleep is primarily regulated by chemoreceptors in the brain stem and carotid bodies, which trigger an increase in respiratory drive in response to a rise in arterial carbon dioxide (PaCO 2 ), thus maintaining PaCO 2 within a narrow range 2,6) . Patients with HF and CSA tend to have an exaggerated respiratory response to carbon dioxide associated with excess sympathetic nervous activity, and so that a modest rise in PaCO 2 that may occur during sleep results in inappropriate hyperventilation 2,7,8) . This drives the PaCO 2 below the 'apneic threshold', at which point the neural drive to respire is too low to stimulate effective inspiration, and an apnea or hypopnea ensues.…”