Bethesda, MD -- Sleep apnea/hypopnea syndrome is characterized by repetitive upper airway obstruction with ensuing cyclical hypoxia, or a decreased level of oxygen in the blood. Repetitive hypoxia is followed by persistently increased ventilatory motor output, commonly referred to as long-term facilitation (LTF). This excitatory mechanism occurs after repetitive stimulation of the carotid bodies as ventilation returns to baseline over a long duration, up to several hours.
Background
LTF is drawn out by repetitive hypoxia during sleep, but only in those who snore regularly and have evidence of inspiratory (timed during inhalation) flow limitation during sleep. Given the occurrence of repetitive hypoxemia in patients with sleep apnea, researchers set out to investigate the occurrence of LTF in patients with obstructive sleep apnea/hypopnea syndrome (OSA).
A new study tested the hypothesis that episodic hypoxic exposure activates LTF in OSA patients during stable non-rapid eye movement (NREM) sleep. The study was undertaken by inducing repetitive hypoxia in OSA patients using nasal continuous positive airway pressure (CPAP) to maintain upper airway patency and stable sleep state for the duration of the experiments.
The authors of the study, “Long-term Facilitation in Obstructive Sleep Apnea Patients During NREM Sleep,” are Salah E. Aboubakr, Amy Taylor, Reason Ford, Sarosh Siddiqi, and M. Safwan Badr, all from the Medical Service, John D. Dingell Veterans Affairs Medical Center, and the Division of Pulmonary/Critical Care and Sleep Medicine, Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan. The study is published in the December 2001 edition of the Journal of Applied Physiology.
Methodology
The 11 test subjects selected or this study had recently documented and untreated sleep apnea. Subjects with other medical problems, such as daytime hypoxemia or cor pulmonale (hypertrophy of the right ventricle resulting from disease of the lungs), were excluded. There were nine men and two women with a mean age of 52.2 ± 10.7 years (range 31-70), body mass index of 33.9 ± 4.0 kg/m2, and apnea/hypopnea index of 43.6 ± 18.7 event/hour.
Night 1. Eleven patients were studied on the first night (N1). The suboptimal pressure was 7.1 ± 2.7 cmH2O. After reaching stage 2 or stage 3 sleep, the subjects breathed room air for five minutes (control period), followed by three minutes of hypoxic gas (eight percent O2); this sequence was repeated 10 timnes. Hypoxia was rapidly induced by having the subject breathe one or two breaths of 100 percent nitrogen followed by continuous eight percent O2 for three minutes to maintain hypoxia (O2 saturation: 80-84 percent). Care was taken to ensure that arterial CO2 pressure remained constant or unchanged throughout the hypoxia period by measuring end-tidal CO2 (PETCO2), and five percent CO2 was supplemented as needed. Hypoxia was abruptly terminated with one breath of 100 percent O2. The breathing pattern was monitored at 5, 20, and 40 minutes of the recovery period after the 10th exposure to hypoxia.
Night 2. Each patient received a nasal CPAP machine set to the optimal volumetric analysis pressure and was asked to use it for a minimum of six hours a night for at least four weeks. After four weeks of treatment with optimal pressure CPAP, eight patients returned for the second night (N2) study, which followed the same protocol as the first night study.
Sham study. Seven patients had a third study during which the CPAP was reiterated to suboptimal pressure (mean = 5 ± 1.4 cmH2O). The pressure was maintained throughout the study night without any hypoxic periods.
Wakefulness/sleep stage was scored according to standard criteria. The subjects were in stable stage 2 or stage 3 (slow wave percentage = 20-25 percent) sleep during the hypoxic exposures and data collection, and there were no arousals found during the data collection periods. Inspired tidal volume, inspiration time (TI), total time for a breath (TT), breathing frequency, PETCO2, and arterial O2 saturation were calculated breath by breath during stable sleep during the first normoxic period (control period) and at five, 20, and 40 min after the 10th hypoxic exposure. Breaths for analysis were selected during a period of stable sleep with no evidence of an arousal by an independent observer. Upper airway resistance was calculated at peak inspiratory flow.
Results
Key findings of the study revealed:
- For the 11 patients under observation during the first night, hypoxia caused increased minute ventilation and decreased upper airway resistance. During the recovery period, decreased upper airway resistance persisted at 5, 20, and 40 min into the recovery period, although the findings returned to control. For the group as a whole, hypoxia resulted in increased one from 11.4 ± 2.6 to 14.8 ± 3.1 l/m (132 percent of control). Supplemental CO2 maintained PETCO2 at near-normoxic levels.
- The decrease in upper airway resistance was not matched by changes in ventilation. During the first night study, the recovery period was 10.7 ± 2.6 l/min. There was no change in tidal volume or breathing frequency.
- An examination of the eight subjects in the second night study using CPAP found that there was no difference in the findings between the first and second night readings. Likewise, there was no change in respiratory frequency or TI. The slight but consistent reduction in TI/TT was the only timing variable to change to a statistically significant degree. Finally, upper airway resistance during the recovery period decreased to 83 ± 9 percent of control.
Conclusions
The researchers found reduced upper airway resistance in the recovery period after repetitive hypoxia. Additionally, they found:
- reduced upper airway resistance in the recovery period indicated LTF of upper airway dilators;
- lack of hyperpnea (breathing that is deeper and more rapid than is normal at rest) in the recovery period, suggesting that thoracic pump muscles do not demonstrate LTF;
- LTF may temporarily stabilize respiration in OSA patients after repeated apneas/hypopneas; and
- nasal CPAP did not alter the ability of OSA patients to elicit LTF at the thoracic pump muscle.
Source
December 2001 edition of the Journal of Applied Physiology.
The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.
Journal
Journal of Applied Physiology