Effect of gender on the development of hypocapnic apnea/hypopnea during NREM sleep.
ABSTRACT We hypothesized that a decreased susceptibility to the development of hypocapnic central apnea during non-rapid eye movement (NREM) sleep in women compared with men could be an explanation for the gender difference in the sleep apnea/hypopnea syndrome. We studied eight men (age 25-35 yr) and eight women in the midluteal phase of the menstrual cycle (age 21-43 yr); we repeated studies in six women during the midfollicular phase. Hypocapnia was induced via nasal mechanical ventilation for 3 min, with respiratory frequency matched to eupneic frequency. Tidal volume (VT) was increased between 110 and 200% of eupneic control. Cessation of mechanical ventilation resulted in hypocapnic central apnea or hypopnea, depending on the magnitude of hypocapnia. Nadir minute ventilation in the recovery period was plotted against the change in end-tidal PCO(2) (PET(CO(2))) per trial; minute ventilation was given a value of 0 during central apnea. The apneic threshold was defined as the x-intercept of the linear regression line. In women, induction of a central apnea required an increase in VT to 155 +/- 29% (mean +/- SD) and a reduction of PET(CO(2)) by -4.72 +/- 0.57 Torr. In men, induction of a central apnea required an increase in VT to 142 +/- 13% and a reduction of PET(CO(2)) by -3.54 +/- 0.31 Torr (P = 0.002). There was no difference in the apneic threshold between the follicular and the luteal phase in women. Premenopausal women are less susceptible to hypocapnic disfacilitation during NREM sleep than men. This effect was not explained by progesterone. Preservation of ventilatory motor output during hypocapnia may explain the gender difference in sleep apnea.
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ABSTRACT: Sleep-disordered Breathing (SDB) is highly prevalent in patients with spinal cord injury (SCI); the exact mechanism(s) or the predictors of disease are unknown. We hypothesized that patients with cervical (C-SCI) are more susceptible to central apnea than patients with thoracic (T-SCI) or able-bodied controls. Methods: Sixteen patients with chronic SCI, level T6 or above, (8 C-SCI, 8 T-SCI) (age 42.5±15.5 years; BMI 25.9±4.9 kg/m(2)) and 16 matched controls were studied. The hypocapnic apneic threshold and CO2 reserve were determined using non-invasive ventilation (NIV). For participants with spontaneous central apnea, CO2 was administered until central apnea was abolished and CO2 reserve was measured as the difference in end-tidal CO2 (PETCO2) before and after. Steady-state plant gain (PG) was calculated from PETCO2 and VE ratio during stable sleep. Controller gain (CG) was defined as the ratio of change in VE between control and hypopnea or apnea to the Δ PETCO2. Results: Central SDB was more common in C-SCI than T-SCI (63% vs. 13%, respectively; p<0.05). Mean CO2 reserve for all participants was narrower in C-SCI than in T- SCI or control group (-0.4±2.9 vs. -2.9±3.3 vs. -3.0±1.2 L/min/mmHg, respectively; p<0.05). PG was higher in C-SCI than in T-SCI or control groups (10.5±2.4 vs. 5.9±2.4 vs. 6.3±1.6 mmHg/L/min, respectively; p<0.05) and CG was not significantly different. The CO2 reserve was an independent predictor of AHI. Conclusion: C-SCI had higher rates of central SDB, indicating that tetraplegia is a risk factor for central sleep apnea. Sleep-related hypoventilation may play a significant role in the mechanism of SDB in higher SCI levels.Journal of Applied Physiology 10/2013; · 3.43 Impact Factor
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ABSTRACT: Spinal cord injury (SCI) is associated with 2-5 times greater prevalence of sleep disordered breathing (SDB) than the general population. The contribution of SCI on sleep and breathing at different levels of injury using two scoring methods has not been assessed. The objectives of this study were to characterize the sleep disturbances in the SCI population and the associated physiological abnormalities using quantitative polysomnography and to determine the contribution of SCI level on the SDB mechanism. We studied 26 consecutive patients with SCI (8 females; age 42.5 ± 15.5 years; BMI 25.9 ± 4.9 kg/m(2); 15 cervical and 11 thoracic levels) by spirometry, a battery of questionnaires and by attended polysomnography with flow and pharyngeal pressure measurements. Inclusion criteria for SCI: chronic SCI (> 6 months post injury), level T6 and above and not on mechanical ventilation. Ventilation, end-tidal CO2 (PETCO2), variability in minute ventilation (VI-CV) and upper airway resistance (RUA) were monitored during wakefulness and NREM sleep in all subjects. Each subject completed brief history and exam, Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Berlin questionnaire (BQ) and fatigue severity scale (FSS). Sleep studies were scored twice, first using standard 2007 American Academy of Sleep Medicine (AASM) criteria and second using new 2012 recommended AASM criteria. Mean PSQI was increased to 10.3 ± 3.7 in SCI patients and 92% had poor sleep quality. Mean ESS was increased 10.4 ± 4.4 in SCI patients and excessive daytime sleepiness (ESS ≥ 10) was present in 59% of the patients. Daytime fatigue (FSS > 20) was reported in 96% of SCI, while only 46% had high-risk score of SDB on BQ. Forced vital capacity (FVC) in SCI was reduced to 70.5% predicted in supine compared to 78.5% predicted in upright positions (p < 0.05). Likewise forced expiratory volume in first second (FEV1) was 64.9% predicted in supine compared to 74.7% predicted in upright positions (p < 0.05). Mean AHI in SCI patients was 29.3 ± 25.0 vs. 20.0 ± 22.8 events/h using the new and conventional AASM scoring criteria, respectively (p < 0.001). SCI patients had SDB (AHI > 5 events/h) in 77% of the cases using the new AASM scoring criteria compared to 65% using standard conventional criteria (p < 0.05). In cervical SCI, VI decreased from 7.2 ± 1.6 to 5.5 ± 1.3 L/min, whereas PETCO2 and VI-CV, increased during sleep compared to thoracic SCI. The majority of SCI survivors have symptomatic SDB and poor sleep that may be missed if not carefully assessed. Decreased VI and increased PETCO2 during sleep in patients with cervical SCI relative to thoracic SCI suggests that sleep related hypoventilation may contribute to the pathogenesis SDB in patients with chronic cervical SCI. Sankari A; Bascom A; Oomman S; Badr MS. Sleep disordered breathing in chronic spinal cord injury. J Clin Sleep Med 2014;10(1):65-72.Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine 01/2014; 10(1):65-72. · 2.93 Impact Factor
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ABSTRACT: Gender differences in the prevalence of sleep apnea/hypopnea syndrome may be mediated via male sex hormones. Our objective was to determine the exact pathway for a testosterone-mediated increased propensity for central sleep apnea via blockade of the 5α-reductase pathway of testosterone conversion by finasteride. Randomization to oral finasteride vs. sham, single-center study. Sleep research laboratory. Fourteen healthy young males without sleep apnea. Hypocapnia was induced via brief nasal noninvasive positive pressure ventilation during stable NREM sleep. Cessation of mechanical ventilation resulted in hypocapnic central apnea or hypopnea. The apnea threshold (AT) was defined as the end-tidal CO2 (PETCO2) that demarcated the central apnea closest to the eupneic PETCO2. The CO2 reserve was defined as the difference in PETCO2 between eupnea and AT. The apneic threshold and CO2 reserve were measured at baseline and repeated after at a minimum of 1 month. Administration of finasteride resulted in decreased serum dihydrotestosterone. In the finasteride group, the eupneic ventilatory parameters were unchanged; however, the AT was decreased (38.9 ± 0.6 mm Hg vs.37.7 ± 0.9 mm Hg, P = 0.02) and the CO2 reserve was increased (-2.5 ± 0.3 mm Hg vs. -3.8 ± 0.5 mm Hg, P = 0.003) at follow-up, with a significantly lower hypocapnic ventilatory response, thus indicating increased breathing stability during sleep. No significant changes were noted in the sham group on follow-up study. Inhibition of testosterone action via the 5α-reductase pathway may be effective in alleviating breathing instability during sleep, presenting an opportunity for novel therapy for central sleep apnea in selected populations. Chowdhuri S; Bascom A; Mohan D; Diamond MP; Badr MS. Testosterone conversion blockade increases breathing stability in healthy men during NREM sleep. SLEEP 2013;36(12):1793-1798.Sleep 01/2013; 36(12):1793-8. · 5.06 Impact Factor