Long-term facilitation in obstructive sleep apnea patients during NREM sleep

Abstract

Repetitive hypoxia followed by persistently increased ventilatory motor output is referred to as long-term facilitation (LTF). LTF is activated during sleep after repetitive hypoxia in snorers. We hypothesized that LTF is activated in obstructive sleep apnea (OSA) patients. Eleven subjects with OSA (apnea/hypopnea index = 43.6 +/- 18.7/h) were included. Every subject had a baseline polysomnographic study on the appropriate continuous positive airway pressure (CPAP). CPAP was retitrated to eliminate apnea/hypopnea but to maintain inspiratory flow limitation (sham night). Each subject was studied on 2 separate nights. These two studies are separated by 1 mo of optimal nasal CPAP treatment for a minimum of 4-6 h/night. The device was capable of covert pressure monitoring. During night 1 (N1), study subjects used nasal CPAP at suboptimal pressure to have significant air flow limitation (>60% breaths) without apneas/hypopneas. After stable sleep was reached, we induced brief isocapnic hypoxia [inspired O(2) fraction (FI(O(2))) = 8%] (3 min) followed by 5 min of room air. This sequence was repeated 10 times. Measurements were obtained during control, hypoxia, and at 5, 20, and 40 min of recovery for ventilation, timing (n = 11), and supraglottic pressure (n = 6). Upper airway resistance (Rua) was calculated at peak inspiratory flow. During the recovery period, there was no change in minute ventilation (99 +/- 8% of control), despite decreased Rua to 58 +/- 24% of control (P < 0.05). There was a reduction in the ratio of inspiratory time to total time for a breath (duty cycle) (0.5 to 0.45, P < 0.05) but no effect on inspiratory time. During night 2 (N2), the protocol of N1 was repeated. N2 revealed no changes compared with N1 during the recovery period. In conclusion, 1) reduced Rua in the recovery period indicates LTF of upper airway dilators; 2) lack of hyperpnea in the recovery period suggests that thoracic pump muscles do not demonstrate LTF; 3) we speculate that LTF may temporarily stabilize respiration in OSA patients after repeated apneas/hypopneas; and 4) nasal CPAP did not alter the ability of OSA patients to elicit LTF at the thoracic pump muscle.

Long-term facilitation of genioglossus activity is present in normal humans during NREM sleep

“…Flow limitation was defined as a plateau in flow despite ≥1 cmH 2 O decrease in the supraglottic pressure. Inspiratory flow limitation (IFL) has been previously described in detail by our laboratory (Rowley et al 2001;Aboubakr et al 2001;Shkoukani et al 2002, Mansour et al 2002.…”

“…Phasic EMG activity was determined from the moving time average. Diaphragm EMG was analyzed similarly (Aboubakr et al 2001). The GG EMG activity was quantified as a percent of maximal activation.…”

“…Although we have not studied GG LTF in sleep apnea patients, it is likely that upper airway dilating muscle (GG) activity was responsible for the decreased upper airway resistance observed in the aftermath of episodic hypoxia (Aboubakr et al 2001) indicating an improvement in upper airway mechanics. The occurrence of GG LTF and the ensuing improvement in upper airway mechanics may represent a protective mechanism mitigating upper airway narrowing and preserving alveolar ventilation following recurrent upper airway obstruction, and episodic hypoxia in sleep apnea.…”

“…The signals were displayed on a polygraph recorder (model 7-D, Grass, West Warwick, RI) and recorded using Biobench data acquisition software (National Instruments, Austin, TX) for further analysis. The above technique has been used previously (Aboubakr et al 2001).…”

“…2004. In contrast, studies from our laboratory have demonstrated LTF in a subset of sleeping humans, specifically, in individuals who snore and who demonstrate inspiratory airflow limitation during sleep, (Babcock and Badr, 1998, Babcock et al 2003, as well as in patients with obstructive sleep apnea (OSA) (Aboubakr et al 2001). Experimental conditions also influence the development of LTF.…”