Am. J. Respir. Crit. Care Med., Volume 162, Number 3, September 2000, 925-929

Serotonergic Stimulation of the Genioglossus and the Response to Nasal Continuous Positive Airway Pressure

JAGADEESHAN SUNDERRAM, RICHARD A. PARISI, and RICHARD J. STROBEL

Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey

In obstructive sleep apnea (OSA), abnormal pharyngeal collapsibility may be offset by increased mechanoreflex-mediated activity of dilator muscles while awake, but this reflex is inhibited during sleep and during application of nasal continuous positive airway pressure (CPAP). Direct activation of upper airway (UA) motor neurons in the hypoglossal nucleus by a selective serotonin reuptake inhibitor (SSRI), paroxetine hydrochloride, may increase genioglossal electromyographic (EMG) activity (EMGgg) in a manner resistant to mechanoreflex inhibition. We studied the effects of paroxetine on EMGgg using an intraoral surface electrode during eupnea or room air breathing (RA), hypercapnia (HYP), and CPAP application in the presence of hypercapnia (CPAP + HYP) in 11 normal volunteers, using a double-blind, placebo-controlled crossover design. After 5 d of paroxetine, EMGgg activity increased significantly within each condition (p = 0.02). EMGgg during the conditions of HYP and HYP + CPAP were significantly greater than during RA for both placebo and paroxetine treatments (p = 0.006). EMGgg activity in HYP persisted during HYP + CPAP on paroxetine (183% versus 182% of placebo, respectively). We conclude that paroxetine produces an augmentation in EMGgg in normal subjects during wakefulness and that this effect persists during mechanoreflex inhibition. This is consistent with a central serotonergic effect.

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