The dynamics of the respiratory and cardiovascular systems were studied by continuously slowing respiration from 0.46 to 0.05 Hz. The time-frequency distribution and global spectral analysis were used to assess the R-R interval (R-R) and the systolic and diastolic blood pressure fluctuations in 16 healthy subjects. During rest, the nonrespiratory-to-respiratory frequency ratios were not affected by occasional slow breathing, whereas the low- (0.01-0.15 Hz) to high- (0.15-0.3 Hz) frequency indexes for blood pressure were increased (P < 0.05). The respiratory fluctuations in R-R and the systolic and diastolic pressures were paced over the 0.46- to 0.05-Hz range. As respiration slowed to 0.07-0.09 Hz, the frequency content of the respiration and cardiovascular variables increased sharply and nonlinearly to a maximum that exceeded values at higher frequencies (P < 0.001). The nonrespiratory frequency content remained stable in the 0.01- to 0.05-Hz range and did not significantly differ from that at rest. In contrast, the nonstable 0.05- to 0.1-Hz component was suppressed. A slow 0.012- to 0.017-Hz rhythm modulated respiration and hemodynamic fluctuations at both respiratory and nonrespiratory frequencies. The study indicated that respiration input should be considered in the interpretation of global spectra. Furthermore the time-frequency distributions demonstrated that a close nonlinear coupling exists between the respiratory and cardiovascular systems.

A B S T R A C T To determine the characteristics of and mechanisms causing the bradycardia during sleep apnea (SA), both patients with SA and normals were studied. Evaluation of six consecutive SA patients demonstrated that bradycardia occurred during 95% of all apneas (central, obstructive, and mixed) and became marked with increased apnea length (P < 0.01) and increased oxyhemoglobin desaturation (P < 0.01). Heart rate slowed 9.5 beats per minute (bpm) during apneas of 10-19 s in duration, 11.4 bpm during 20-39-s apneas, and 16.6 bpm during 40-59-s apneas. Sleep stage had no effect unexplained by apnea length or degree of desaturation.Oxygen administration to four SA patients completely prevented the bradycardia although apneas lengthened (P < 0.05) in three. Sleeping normal subjects did not develop bradycardia during hypoxic hyperpnea but, instead, HR increased with hypoxia in all sleep stages, although the increase in HR was not as great as that which occurred while awake.Breath holding in awake normals did not result in bradycardia during hyperoxia (SaO2 = 99%), but was consistently (P < 0.01) associated with heart rate slowing during room air breath-holds (-6 bpm) at SaO2 = 93%, with more striking slowing (-20 bpm) during hypoxic breath-holds (P < 0.01) at SaO2 = 78%. Breath holding during hyperoxic hypercapnia had no significant effect on rate. Breath holding in awake SA subjects demonstrated similar findings. We conclude that the bradycardia of SA is a consistent feature of apnea and results from the combined effect of cessation of breathing plus hypoxemia.

The purposes of this investigation were to describe the changes in 1) dynamic compliance of the lungs, 2) airflow resistance, and 3) breathing pattern that occur during sleep in normal adult humans. Six subjects wore a tightly fitting face mask. Flow and volume were obtained from a pneumotachograph attached to the face mask. Transpulmonary pressure was calculated as the difference between esophageal pressure obtained with a balloon and mask pressure. At least 20 consecutive breaths were analyzed for dynamic compliance, airflow resistance, and breathing pattern during wakefulness, non-rapid-eye-movement stage 2 and rapid-eye-movement (REM) sleep. Dynamic compliance did not change significantly. Airflow resistance increased during sleep; resistance was 3.93 +/- 0.56 cmH2O X 1–1 X s during wakefulness, 7.96 +/- 0.95 in stage 2 sleep, and 8.66 +/- 1.43 in REM sleep (P less than 0.02). By placing a catheter in the retroepiglottic space and thus dividing the airway into upper and lower zones, we found the increase in resistance occurred almost entirely above the larynx. Decreases in tidal volume, minute ventilation, and mean inspiratory flow observed during sleep were not statistically significant.

To assess the effect of sleep on functional residual capacity (FRC) in normal subjects and asthmatic patients, 10 adult subjects (5 asthmatic patients with nocturnal worsening, 5 normal controls) were monitored overnight in a horizontal volume-displacement body plethysmograph. With the use of a single inspiratory occlusion technique, we determined that when supine and awake, asthmatic patients were hyperinflated relative to normal controls (FRC = 3.46 +/- 0.18 and 2.95 +/- 0.13 liters, respectively; P less than 0.05). During sleep FRC decreased in both groups, but the decrease was significantly greater in asthmatic patients such that during rapid-eye-movement (REM) sleep FRC was equivalent between the asthmatic and normal groups (FRC = 2.46 +/- 0.23 and 2.45 +/- 0.09 liters, respectively). Specific pulmonary conductance decreased progressively and significantly in the asthmatic patients during the night, falling from 0.047 +/- 0.007 to 0.018 +/- 0.002 cmH2O-1.s-1 (P less than 0.01). There was a significant linear relationship through the night between FRC and pulmonary conductance in only two of the five asthmatic patients (r = 0.55 and 0.65, respectively). We conclude that 1) FRC falls during sleep in both normal subjects and asthmatic patients, 2) the hyperinflation observed in awake asthmatic patients is diminished during non-REM sleep and eliminated during REM sleep, and 3) sleep-associated reductions in FRC may contribute to but do not account for all the nocturnal increase in airflow resistance observed in asthmatic patients with nocturnal worsening.

The purpose of this study was to determine whether hypoventilation contributes to the sleep hypoxemia observed in chronic obstructive pulmonary disease (COPD) patients and to examine breathing pattern and respiratory muscle electromyographic (EMG) activity during these episodes. Seven COPD patients who experienced at least a 10% decrease in arterial O2 saturation (SaO2) during rapid-eye-movement sleep (REM) sleep, six COPD patients with a minimal fall in SaO2, and five healthy subjects were studied. An inductance vest was used to quantitate ventilation. Skin electrodes were used to estimate diaphragmatic and intercostal electromyographic activity. Minute ventilation and EMG activity decreased in all three groups during sleep. Ventilation was irregular during REM sleep in the patients. During REM sleep, desaturating patients had longer episodes of hypopneic breathing [30 +/- 8 s (SE)] than nondesaturating patients (13 +/- 1 s, P less than 0.01). Desaturating patients spent a greater proportion of REM time hypopneic (53 +/- 5 vs. 28 +/- 5%, P less than 0.01) and had a greater decrease in functional residual capacity during hypopnea (P less than 0.05). SaO2 followed the hypopneic and hyperpneic breathing in REM sleep so that desaturating patients had more time for desaturation to occur. Thus hypoventilation appears to be a primary factor in sleep O2 desaturation in these patients. Because of the fall in lung volume, maldistribution of ventilation may also contribute.

The effect of an increased end-expiratory lung volume on inspiratory and expiratory duration was examined in 13 term infants at 4, 30, and 70 h of age. This was accomplished by the administration of a continuous positive airway pressure (CPAP) of 0, 3, and 6 cmH2O by use of a face mask connected to a pneumotachometer, and by measurement of the timing of the respiratory cycle over 1-min intervals. At increasing functional residual capacity (FRC) there was a progressive increase in expiratory time (TE) and fall in respiratory rate, with a variable effect on inspiratory time (TI). As CPAP increased from 0 to 6 cmH2O, the TI/TE ratio fell from 0.75 to 0.62 (P less than 0.01), 0.90 to 0.66 (P less than 0.001), and 0.87 to 0.64 (P less than 0.001) at 4, 30, and 70 h, respectively. We conclude that alterations in end-expiratory lung volume significantly alter expiratory duration in the newborn infant at term. This may be analogous to the vagally mediated tonic control of expiratory time with changing FRC recently described in anesthetized animals.

To characterize ventilatory responses to bronchoconstriction during sleep and to assess the effect of prior sleep deprivation on ventilatory and arousal responses to bronchoconstriction, bronchoconstriction was induced in eight asthmatic subjects while they were awake, during normal sleep, and during sleep after a 36-h period of sleep deprivation. Each subject was bronchoconstricted with increasing concentrations of aerosolized methacholine while ventilatory patterns and lower airway resistance (Rla) were continually monitored. The asthmatic patients maintained their minute ventilation as Rla increased under all conditions, demonstrating a stable tidal volume with a mild increase in respiratory frequency. Inspiratory drive, as measured by occlusion pressure (P0.1), increased progressively and significantly as Rla increased under all conditions (slopes of P0.1 vs. Rla = 0.249, 0.112, and 0.154 for awake, normal sleep, and sleep after sleep deprivation, respectively, P less than 0.0006). Chemostimuli did not appear to contribute significantly to the observed increases in P0.1. Prior sleep deprivation had no effect on ventilatory and P0.1 responses to bronchoconstriction but did significantly raise the arousal threshold to induced bronchoconstriction. We conclude that ventilatory responses to bronchoconstriction, unlike extrinsic loading, are not imparied by the presence of sleep, nor are they chemically mediated. However, prior sleep deprivation does increase the subsequent arousal threshold.

The transient ventilatory responses to hypercapnia were studied in nine healthy preterm infants. We administered 4% CO2 in air for at least 7 min during quiet sleep and measured frequency (f), inspiratory time (TI), expiratory time (TE), tidal volume (VT), and minute ventilation (VI). Frequency increased over the first 2 min of CO2 inhalation (P less than 0.05) and then decreased to control values (P less than 0.05). This response was secondary to changes in TE, which decreased over the first 2 min (P less than 0.05) and then returned to control values, whereas TI did not change. The late increase in TE was associated with an increased percent of breaths exhibiting retardation of expiratory flow (braking) (P less than 0.05). These breaths had longer TE than the breaths without braking (P less than 0.05). Exponential curves made to fit the increases in VI and VT revealed that only 67% of the infants reached 90% of steady state for both VI and VT over the 7-min study period. The time to 90% of steady state was always shorter for VI than VT (P less than 0.05) due to the transient changes in f. The results indicate that the transient changes of f in response to hypercapnia are secondary to changes in TE, which appear unique to human infants. We speculate that the expiratory braking that develops during the course of CO2 inhalation increases lung volume, resulting in prolongation of TE via mechanoreceptor-mediated reflexes.