Determinants of Age Related Breathing Instability During Non-Rapid-Eye-Movement (NREM) Sleep

• Long-term facilitation [ Time Frame: 4-6 wks for each participant ] [ Designated as safety issue: No ]
• Upper airway resistance [ Time Frame: 4-6 wks for each participant ] [ Designated as safety issue: No ]

The purpose for our research protocol is to examine the role of breathing control mechanisms that determine the development of sleep-disordered breathing in the elderly. This proposal will focus on key factors that contribute to the control of ventilation in healthy individuals and in subjects with sleep-disordered breathing. We will study the age-specific changes in both normal persons and sleep individuals with sleep apnea.

Sleep apnea-hypopnea syndrome (SAS) is a relatively common disorder in the US population with significant adverse health consequences. Despite the high prevalence of SAS in elderly individuals, the underlying mechanisms have remained elusive. Specifically, we do not know whether the high prevalence of sleep apnea in older adults is due to increased central breathing instability. This proposal focuses on investigating age-specific differences in the susceptibility to central breathing instability in healthy individuals as well as individuals with sleep apnea.

This project will investigate the following specific objectives:

• Determine age-specific changes in the hypocapnic apneic threshold during sleep in

  • elderly vs young individuals without sleep apnea
  • elderly vs young individuals with sleep apnea.

• Determine age-specific changes in long-term facilitation during sleep in

  • elderly versus young individuals without sleep apnea
  • elderly vs young individuals with sleep apnea.
• We will investigate the susceptibility to central breathing instability by mechanically ventilating the subjects during NREM sleep using pressure support ventilation. We will compare the hypocapnic apneic threshold in old (age>60-65 years) and young (age 18-40years) individuals who are healthy as well as in those with sleep-disordered breathing. We will also measure the parameters over a continuum of age from 18 to 89y.
• We will investigate whether there is a difference in the susceptibility to long term facilitation of genioglossus activity and ventilation between young and old healthy individuals in response to episodic hypoxia, while maintaining isocapnia. We will conduct similar experiments in young and old individuals with sleep apnea.

Sleep apnea is very common in older veterans and is associated with significant cardiovascular complications. Greater insight into the pathogenesis will have a positive impact on the health of veterans suffering from this condition. This proposal will further our understanding of the pathogenesis of breathing instability leading to sleep-disordered breathing during sleep. Thus, we anticipate our findings will provide a basis for new approaches to prevention and management of SAS in veterans.

• Sleep Apnea
• Age

• Arm 1
  Young adults, age 18-40 yrs
  Intervention: Other: hyperventilation and episodic hypoxia
• Experimental: Arm 2
  Older adults, age >40-65yrs
  Intervention: Other: hyperventilation and episodic hypoxia

Inclusion Criteria:

• Normal subjects without sleep apnea (controls) and individuals with sleep apnea.

Exclusion Criteria:

• Pregnancy,
• history of active coronary artery disease-including stable and unstable angina,
• myocardial infarction,
• history of congestive heart failure,
• stroke, who have excessive daytime sleepiness with Epworth Sleepiness Scale of >15 will not be included in the study
• patient with OSA who
• depression,
• schizophrenia,
• untreated hypothyroidism,
• diabetes on insulin,
• seizure disorder,
• intrinsic renal and liver disorders,
• failure to give informed consent,
• patients with evidence of pulmonary diseases based on history and abnormal pulmonary function testing, including obstructive (ratio of predicted forced expiratory volume to forced vital capacity, <80% predicted) or restrictive lung disorders (total lung capacity <80% predicted) with resting oxygen saturation of <96% and kyphoscoliosis (chest wall deformities) will be excluded,
• patients on certain medications including, opiates derivatives, stimulants, antidepressants, tranquilizers, anti-psychotic agents, theophylline and other central nervous system altering medications will be ineligible,
• history of alcohol or recreational drug use will also serve as grounds for exclusion,
• patients with body mass index (BMI) >34kg/m2 will be excluded,
• subjects with sleep apnea are already using continuous positive airway pressure for more than 7 days as therapy will not be eligible.