Obstructive sleep apnea (OSA) is common and has major health implications but treatment
options are limited. OSA patients show a marked reduction in upper airway (UA) dilator
muscle activity at sleep onset and this phenomenon leads to increased collapsibility of UA
compared to normal subjects. Until recently, the search for medicines to activate pharyngeal
muscles in sleeping humans has been discouraging. However, exciting new animal research has
shown that drugs with noradrenergic and antimuscarinic effects can restore pharyngeal muscle
activity to waking levels. In this protocol the investigators will test the effect of
desipramine (a tricyclic antidepressant with strong noradrenergic and antimuscarinic
effects) on genioglossus muscle activity (EMG GG) during sleep in healthy control subjects.
Two overnight sleep studies, a placebo night and a drug night, will be performed
approximately one week apart in random order. The placebo or drug will be administered 2
hours before lights out. At least 15 minutes of quiet wakefulness will be recorded to
quantify the subject's awake EMG GG activity. Subjects will then sleep in the lateral
position to minimize pharyngeal resistance similar to previous studies of this kind.
The same will be done for stable NREM and REM sleep (free of arousals and other artifacts).
Both NREM and REM sleep will be analyzed, recognizing that REM is less frequent on these
During the second part of the night, the subjects will be connected to a modified continuous
positive airway pressure (CPAP) machine (Pcrit3000, Respironics) which can provide a wide
range of pressures between 20 and -20 cmH2O in order to modify upper airway pressure and
measure change in EMG GG as a function of epiglottic pressure (muscle responsiveness).
- Healthy control subjects
- Cardiovascular disease other than well controlled hypertension