Effects of 12 Months Continuous Positive Airway Pressure on Sympathetic Activity Related Brainstem Function and Structure in Obstructive Sleep Apnea.

Luke A Henderson,Vaughan G Macefield,David K Mckenzie,Rania H Fatouleh,Linda C Lundblad

doi:10.3389/fnins.2016.00090

Abstract

Muscle sympathetic nerve activity (MSNA) is greatly elevated in patients with obstructive sleep apnea (OSA) during normoxic daytime wakefulness. Increased MSNA is a precursor to hypertension and elevated cardiovascular morbidity and mortality. However, the mechanisms underlying the high MSNA in OSA are not well understood. In this study we used concurrent microneurography and magnetic resonance imaging to explore MSNA-related brainstem activity changes and anatomical changes in 15 control and 15 OSA subjects before and after 6 and 12 months of continuous positive airway pressure (CPAP) treatment. We found that following 6 and 12 months of CPAP treatment, resting MSNA levels were significantly reduced in individuals with OSA. Furthermore, this MSNA reduction was associated with restoration of MSNA-related brainstem activity and structural changes in the medullary raphe, rostral ventrolateral medulla, dorsolateral pons, and ventral midbrain. This restoration occurred after 6 months of CPAP treatment and was maintained following 12 months CPAP. These findings show that continual CPAP treatment is an effective long-term treatment for elevated MSNA likely due to its effects on restoring brainstem structure and function.

Highlights

Obstructive sleep apnea (OSA) is characterized by repetitive complete or partial cessation of airflow during sleep, owing to collapse of the upper airways
We found that OSA patients used continuous positive airway pressure (CPAP) for an average of 5.5 ± 0.3 h/night during the first 6 month period and 5.5 ± 0.3 h/night during the 6–12 month period and there was a significant reduction in apnea-hypopnea index (AHI) after 6 months of CPAP treatment (AHI 3.0 ± 0.8; range 0.6–9.9) which reduced further after 12 months treatment (AHI 1.6 ± 0.4; range 0.3– 7.1)
We found that the increase in resting muscle sympathetic nerve activity (MSNA) in individuals with OSA was significantly reduced toward control levels following 6 and 12 months of CPAP treatment

Summary

Introduction

Obstructive sleep apnea (OSA) is characterized by repetitive complete or partial cessation of airflow during sleep, owing to collapse of the upper airways. Brainstem Changes in OSA individuals with OSA display significant gray matter volumetric changes, primarily gray matter concentration reductions in numerous higher brain regions, including some that can significantly modulate changes in MSNA (Macey et al, 2002; Morrell et al, 2003; Canessa et al, 2011) Some of these studies have shown that OSA is associated with altered arterial pressure and heart rate responses during numerous challenges and these altered responses appear to be associated with alterations in regional brain activity (Harper et al, 2003, 2012; Henderson et al, 2003; Macey et al, 2003, 2006). These studies investigated evoked changes in brain activity during various cardiovascular challenges, they did not explore brain sites responsible for the increased resting MSNA and associated hypertension in individuals with OSA

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