Biomedical subjects

M S Badr

Publications and source records attributed to M S Badr.

35 records · Page 2Linked to original sources

PubMed1996

Effect of ventilatory drive on upper airway patency in humans during NREM sleep.

The pharynx is the site of upper airway obstruction during sleep. As a collapsible tube, pharyngeal patency is determined by transmural pressure and the compliance of the pharyngeal wall. Thus, several factors may influence upper airway patency including the activity of upper airway dilating muscles, the magnitude of caudal traction generated by thoracic inspiratory activity, vascular tone and mucosal surface forces. Changing ventilatory motor output influences upper airway patency primarily by altering dilating muscle activity or caudal traction. Increased ventilatory motor output enhances upper airway patency. Isolated reduction of ventilatory motor output has no significant effect on upper airway patency. However, upper airway narrowing or occlusion occur at the nadir of ventilatory drive during induced periodic breathing and during central apnea. The latter indicates that negative intraluminal pressure is not required for upper airway obstruction during sleep. Therefore, upper airway occlusion during sleep may be due to: (1) passive collapse of a compliant upper airway by gravitational factors or (2) active closure generated by the contraction of the pharyngeal constrictors.

Airway Obstruction↗

PubMed1996

Post-hyperventilation hypopnea in humans during NREM sleep.

We wished to determine if mild hypocapnia above the "apneic threshold" would result in apnea or hypopnea during NREM sleep. Hypocapnia was induced by nasal mechanical hyperventilation for 1 min either under normoxia (51 trials, n = 7) or hyperoxia (43 trials, n = 5). Cessation of mechanical ventilation resulted in hypopnea due to reduced VT without a change in f. Central apnea occurred mostly under hyperoxic conditions (9/43 versus 2/51 trials under normoxic conditions), and only when complete inhibition of ventilatory motor output occurred during mechanical ventilation. Significant correlation between the magnitude of hypocapnia and nadir VE was noted under both normoxic and hyperoxic conditions. However, nadir VE was variable when hypocapnia was modest (-2 mmHg); further hypocapnia (-4 mmHg) was associated with consistent reduction in nadir VE below 30% of control under normoxic conditions, and central apnea under hyperoxic conditions. We conclude that: (1) Brief hyperventilation during NREM sleep is followed by hypocapnic hypopnea due to reduced VT and not breathing frequency; (2) Hypocapnia due to brief mild hyperventilation does not cause central apnea unless peripheral chemoreceptors are also inhibited; (3) Sustained hyperventilation or more severe hypocapnia may be required for the development of hypocapnic central apnea during NREM sleep.

Adult↗

PubMed1996

Neurocirculatory consequences of abrupt change in sleep state in humans.

The arterial pressure elevations that accompany sleep apneas may be caused by chemoreflex stimulation, negative intrathoracic pressure, and/or arousal. To assess the neurocirculatory effects of arousal alone, we applied graded auditory stimuli during non-rapid-eye-movement (NREM) sleep in eight healthy humans. We measured muscle sympathetic nerve activity (intraneural microelectrodes), electroencephalogram (EEG; C4/A1 and O1/A2), arterial pressure (photoelectric plethysmography), heart rate (electrocardiogram), and stroke volume (impedance cardiography). Auditory stimuli caused abrupt increases in systolic and diastolic pressures (21 +/- 2 and 15 +/- 1 mmHg) and heart rate (11 +/- 2 beats/min). Cardiac output decreased (-10%). Stimuli that produced EEG evidence of arousal evoked one to two large bursts of sympathetic activity (316 +/- 46% of baseline amplitude). Stimuli that did not alter EEG frequency produced smaller but consistent pressor responses even though no sympathetic activation was observed. We conclude that arousal from NREM sleep evokes a pressor response caused by increased peripheral vascular resistance. Increased sympathetic outflow to skeletal muscle may contribute to, but is not required for, this vasoconstriction. The neurocirculatory effects of arousal may augment those caused by asphyxia during episodes of sleep-disordered breathing.

Adult↗

PubMed1995

The assessment of upper airway patency during apnea using cardiogenic oscillations in the airflow signal.

We investigated the relationship between airway patency and the occurrence of cardiogenic related oscillations in the airflow signal during 67 apneas occurring in non-rapid eye movement sleep in eight subjects. Spontaneously occurring apneas and apneas induced by mechanical ventilation were analyzed. Airway occlusion was determined by direct observation of the pharyngeal lumen using fiberoptic endoscopy. The presence or absence of cardiogenic oscillations was determined from an expanded airflow signal by an investigator blinded to the airway patency. Of the total 67 apneas, complete airway occlusion occurred during 51, and the airway remained patent throughout in 16. Cardiogenic oscillations were seen throughout 39 of the 51 occluded apneas and throughout 9 of the 16 apneas with the airway patent. There was no relationship between the occurrence of cardiogenic oscillations and airway patency. In addition, in a canine model where the upper airway was anatomically isolated, cardiogenic oscillations were evident during apneas in pressure signals recorded from the isolated upper airway and in airflow signals at the tracheal stoma. We conclude that cardiogenic oscillations cannot be used to predict airway patency during apnea.

Adult↗

PubMed1995

Pharyngeal narrowing/occlusion during central sleep apnea.

We hypothesized that subatmospheric intraluminal pressure is not required for pharyngeal occlusion during sleep. Six normal subjects and six subjects with sleep apnea or hypopnea (SAH) were studied during non-rapid-eye-movement sleep. Pharyngeal patency was determined by using fiber-optic nasopharyngoscopy during spontaneous central sleep apnea (n = 4) and induced hypocapnic central apnea via nasal mechanical ventilation (n = 10). Complete pharyngeal occlusion occurred in 146 of 160 spontaneously occurring central apneas in patients with central sleep apnea syndrome. During induced hypocapnic central apnea, gradual progressive pharyngeal narrowing occurred. More pronounced narrowing was noted at the velopharynx relative to the oropharynx and in subjects with SAH relative to normals. Complete pharyngeal occlusion frequently occurred in subjects with SAH (31 of 44 apneas) but rarely occurred in normals (3 of 25 apneas). Resumption of inspiratory effort was associated with persistent narrowing or complete occlusion unless electroencephalogram signs of arousal were noted. Thus pharyngeal cross-sectional area is reduced during central apnea in the absence of inspiratory effort. Velopharyngeal narrowing consistently occurs during induced hypocapnic central apnea even in normal subjects. Complete pharyngeal occlusion occurs during spontaneous or induced central apnea in patients with SAH. We conclude that subatmospheric intraluminal pressure is not required for pharyngeal occlusion to occur. Pharyngeal narrowing or occlusion during central apnea may be due to passive collapse or active constriction.

Adult↗

PubMed1994

Smoking as a risk factor for sleep-disordered breathing.

BACKGROUND: Recent evidence indicates that the prevalence of sleep-disordered breathing is remarkably high (24% for men and 9% for women) and that the public health burden attributable to sleep-disordered breathing is substantial. This investigation examines current and former cigarette smoking as potential risk factors for sleep-disordered breathing. METHODS: Data were from 811 adults enrolled in the University of Wisconsin Sleep Cohort Study, Madison. The Sleep Cohort Study is a longitudinal, epidemiologic study that uses nocturnal polysomnography to investigate sleep-disordered breathing and other disorders of sleep. The presence and severity of sleep-disordered breathing was quantified by the frequency of apneas and hypopneas per hour of sleep. RESULTS: Logistic regression analyses were used to control for potential confounding factors. Compared with never smokers, current smokers had a significantly greater risk of snoring (odds ratio, 2.29) and of moderate or worse sleep-disordered breathing (odds ratio, 4.44). Heavy smokers (> or = 40 cigarettes per day) had the greatest risk of mild sleep-disordered breathing (odds ratio, 6.74) and of moderate or worse sleep-disordered breathing (odds ratio, 40.47). Former smoking was unrelated to snoring and sleep-disordered breathing after adjustment for confounders. CONCLUSIONS: Current cigarette smokers are at greater risk for sleep-disordered breathing than are never smokers. Heavy smokers have the greatest risk while former smokers are not at increased risk for sleep-disordered breathing. Thus, smoking cessation should be considered in the treatment and prevention of sleep-disordered breathing.

Adult↗

PubMed1994

Effect of chemoreceptor stimulation and inhibition on total pulmonary resistance in humans during NREM sleep.

We investigated the effect of chemoreceptor stimulation and inhibition on total pulmonary resistance (RL) during non-rapid-eye-movement (NREM) sleep in healthy subjects. Chemoreceptor stimulation was accomplished with brief isocapnic hypoxia (n = 8). Minute ventilation increased to 150% of room air control. RL at peak inspiratory flow decreased to 66% of room air control. Resistive pressure-inspiratory flow plots demonstrated lower resistive pressures for a given inspiratory flow. Chemoreceptor inhibition was accomplished by abruptly terminating brief hypocapnic hypoxia with 100% O2 (n = 7). Minute ventilation decreased to 63% of room air control. RL calculated at peak inspiratory or fixed flow did not change significantly, and pressure-flow plots at nadir ventilation showed no systematic change from room air control. We conclude that 1) hypoxic chemoreceptor stimulation is associated with decreased RL and enhancement of pressure-flow relationships, suggesting increased upper airway caliber; 2) upper airway patency is not compromised during periods of low ventilatory drive in normal subjects; and 3) upper airway dilating muscles and thoracic pump muscles are optionally coordinated with increased and decreased ventilatory drive.

Adult↗

PubMed1994

Treatment of refractory sleep apnea with supplemental carbon dioxide.

Sleep apnea syndrome is a relatively common disorder characterized by periodic cessation of breathing during sleep because of upper airway obstruction (obstructive sleep apnea) or by reduction of ventilatory drive (central sleep apnea). We report the case of a middle-aged, obese man who underwent tracheostomy for the treatment of obstructive sleep apnea documented by polysomnography. Although tracheostomy resulted in marked clinical improvement, relief of upper airway obstruction unmasked severe central sleep apnea. We report the successful treatment of this patient's central sleep apnea syndrome with the use of supplemental CO2 therapy.

Adult↗

PubMed1994

Impact of the aging pulmonary system on the response to exercise.

The older adult demonstrates several alterations in the ventilatory response to exercise relative to the young adult. These differences are primarily caused by the aging-induced loss of elastic recoil of the lung, which reduces expiratory airflow rates along the effort-independent portion of the maximal volitional flow-volume envelope. Despite these distinctions in the response to exercise of the aged adult, alveolar ventilation is adequate for carbon dioxide elimination (even during maximal exercise), and arterial oxygen homeostasis is generally maintained.

Adult↗

PubMed1992

Load compensation and respiratory muscle function during sleep.

The sleeping state places unique demands on the ventilatory control system. The sleep-induced increase in airway resistance, the loss of consciousness, and the need to maintain the sleeping state without frequent arousals require the presence of complex compensatory mechanisms. The increase in upper airway resistance during sleep represents the major effect of sleep on ventilatory control. This occurs because of a loss of muscle activity, which narrows the airway and also makes it more susceptible to collapse in response to the intraluminal pressure generated by other inspiratory muscles. The magnitude and timing of the drive to upper airway vs. other inspiratory pump muscles determine the level of resistance and can lead to inspiratory flow limitation and complete upper airway occlusion. The fall in ventilation with this mechanical load is not prevented, as it is in the awake state, because of the absence of immediate compensatory responses during sleep. However, during sleep, compensatory mechanisms are activated that tend to return ventilation toward control levels if the load is maintained. Upper airway protective reflexes, intrinsic properties of the chest wall, muscle length-compensating reflexes, and most importantly chemoresponsiveness of both upper airway and inspiratory pump muscles are all present during sleep to minimize the adverse effect of loading on ventilation. In non-rapid-eye-movement sleep, the high mechanical impedance combined with incomplete load compensation causes an increase in arterial PCO2 and augmented respiratory muscle activity. Phasic rapid-eye-movement sleep, however, interferes further with effective load compensation, primarily by its selective inhibitory effects on the phasic activation of postural muscles of the chest wall. The level and pattern of ventilation during sleep in health and disease states represent a compromise toward the ideal goal, which is to achieve maximum load compensation and meet the demand for chemical homeostasis while maintaining sleep state.

Animals↗

PubMed1992

Determinants of poststimulus potentiation in humans during NREM sleep.

To test whether active hyperventilation activates the "afterdischarge" mechanism during non-rapid-eye-movement (NREM) sleep, we investigated the effect of abrupt termination of active hypoxia-induced hyperventilation in normal subjects during NREM sleep. Hypoxia was induced for 15 s, 30 s, 1 min, and 5 min. The last two durations were studied under both isocapnic and hypocapnic conditions. Hypoxia was abruptly terminated with 100% inspiratory O2 fraction. Several room air-to-hyperoxia transitions were performed to establish a control period for hyperoxia after hypoxia transitions. Transient hyperoxia alone was associated with decreased expired ventilation (VE) to 90 +/- 7% of room air. Hyperoxic termination of 1 min of isocapnic hypoxia [end-tidal PO2 (PETO2) 63 +/- 3 Torr] was associated with VE persistently above the hyperoxic control for four to six breaths. In contrast, termination of 30 s or 1 min of hypocapnic hypoxia [PETO2 49 +/- 3 and 48 +/- 2 Torr, respectively; end-tidal PCO2 (PETCO2) decreased by 2.5 or 3.8 Torr, respectively] resulted in hypoventilation for 45 s and prolongation of expiratory duration (TE) for 18 s. Termination of 5 min of isocapnic hypoxia (PETO2 63 +/- 3 Torr) was associated with central apnea (longest TE 200% of room air); VE remained below the hyperoxic control for 49 s. Termination of 5 min of hypocapnic hypoxia (PETO2 64 +/- 4 Torr, PETCO2 decreased by 2.6 Torr) was also associated with central apnea (longest TE 500% of room air). VE remained below the hyperoxic control for 88 s. We conclude that 1) poststimulus hyperpnea occurs in NREM sleep as long as hypoxia is brief and arterial PCO2 is maintained, suggesting the activation of the afterdischarge mechanism; 2) transient hypocapnia overrides the potentiating effects of afterdischarge, resulting in hypoventilation; and 3) sustained hypoxia abolishes the potentiating effects of after-discharge, resulting in central apnea. These data suggest that the inhibitory effects of sustained hypoxia and hypocapnia may interact to cause periodic breathing.

Carbon Dioxide↗

PubMed1991

Effect of sleep-induced increases in upper airway resistance on respiratory muscle activity.

To investigate the response of inspiratory and expiratory muscles to naturally occurring inspiratory resistive loads in the absence of conscious control, five male "snorers" were studied during non-rapid-eye-movement (NREM) sleep with and without continuous positive airway pressure (CPAP). Diaphragm (EMGdi) and scalene (EMGsc) electromyographic activity were monitored with surface electrodes and abdominal EMG activity (EMGab) with wire electrodes. Subjects were studied in the following conditions: 1) awake, 2) stage 2 sleep, 3) stage 3/4 sleep, 4) CPAP during stage 3/4 sleep, 5) CPAP plus end-tidal CO2 pressure (PETCO2) isocapnic to stage 2 sleep, and 6) CPAP plus PETCO2 isocapnic to stage 3/4 sleep. Inspired pulmonary resistance (RL) at peak flow rate and PETCO2 increased in all stages of sleep. Activity of EMGdi, EMGsc, and EMGab increased significantly in stage 3/4 sleep. CPAP reduced RL at peak flow, increased tidal volume and expired ventilation, and reduced PETCO2. EMGdi and EMGsc were reduced, and EMGab was silenced. During CPAP, with CO2 added to make PETCO2 isocapnic to stage 3/4 sleep, EMGsc and EMGab increased, but EMGdi was augmented in only one-half of the trials. EMG activity in this condition, however, was only 75% (EMGsc) and 43% (EMGab) of the activity observed during eupneic breathing in stage 3/4 sleep when PETCO2 was equal but RL was much higher. We conclude that during NREM sleep 1) inspiratory and expiratory muscles respond to internal inspiratory resistive loads and the associated dynamic airway narrowing and turbulent flow developed throughout inspiration, 2) some of the augmentation of respiratory muscle activity is also due to the hypercapnia that accompanies loading, and 3) the abdominal muscles are the most sensitive to load and CO2 and the diaphragm is the least sensitive.

Airway Resistance↗

PubMed1991

Effect of hypercapnia on total pulmonary resistance during wakefulness and during NREM sleep.

We investigated the effect of different levels of hypercapnia on total pulmonary resistance (RL) in 13 subjects ranging from nonsnorers with low RL to snorers with high RL and dynamic narrowing of the upper airway during inspiration. Added CO2 was adjusted to achieve a steady-state increase in PETCO2 of +2, +4, or +6 mm Hg. RL was measured at peak inspiratory flow (RLpf), at maximal resistance within breath (RLmax), and at 10 equally spaced points within inspiration in several trials. During wakefulness, hypercapnia was associated with decreased RLmax. During steady state +6 mm Hg hypercapnia, RLmax decreased by 30% (p less than 0.01). During NREM sleep, low levels of hypercapnia did not affect RL. However, +6 mm Hg hypercapnia was associated with decreased RLmax in six of eight subjects (p = 0.07), especially in subjects with high RLmax during room air breathing. The effects of hypercapnia on RLpf paralleled its effect on RLmax. We concluded that (1) the decrease in RL during awake hypercapnia suggests an increase in upper airway dimensions and stiffness, (2) the absence of increased RL during low level NREM hypercapnia (despite the increase in inspiratory flows and collapsing pressures) also suggests an increase in upper airway dimensions and stiffness, and (3) upper airway dilating muscles appear to be recruited in a coordinated fashion with inspiratory muscles in normal humans during NREM sleep. The implications of these findings in patients with obstructive sleep apnea are not clear at this point.

Airway Resistance↗

PubMed1991

Role of airway mechanoreceptors in the inhibition of inspiration during mechanical ventilation in humans.

The purpose of this study was to demonstrate a neuromechanical inhibitory effect on respiratory muscle activity during mechanical ventilation and to determine whether upper and lower airway receptors provide this inhibitory feedback. Several protocols were completed during mechanical ventilation: (1) positive and negative pressure changes in the upper airway, (2) airway anesthesia to examine the consequences of receptor blockade on respiratory muscle activity, (3) increasing FRC with positive end-expiratory pressure to study the effect of hyperinflation or stretch on respiratory muscle activity, and (4) use of heart-lung transplant patients to determine the effects of vagal denervation on respiratory muscle activity. All subjects were mechanically hyperventilated with positive pressure until inspiratory muscle activity was undetectable and the end-tidal PCO2 decreased to less than 30 mm Hg. End-tidal PCO2 (PETCO2) was increased by either adding CO2 to the inspired gas or decreasing tidal volume (50 ml/min). The PETCO2 where a change in inspiratory muscle activity occurred was taken as the recruitment threshold (PCO2RT). Neuromechanical feedback caused significant inspiratory muscle inhibition during mechanical ventilation, as evidenced by the difference between PCO2RT and PETCO2 during spontaneous eupnea (45 +/- 4 versus 39 +/- 4 mm Hg) and a lower PCO2RT when tidal volume was reduced with a constant frequency and fraction of inspired CO2. Recruitment threshold was unchanged during positive and negative pressure ventilation, during upper and lower airway anesthesia, and in vagally denervated lung transplant patients. These findings demonstrate that neuromechanical feedback causes highly significant inhibition of inspiratory muscle activity during mechanical ventilation; upper and lower airway receptors do not appear to mediate this effect.

Adult↗

PubMed1990

Effect of mechanical loading on expiratory and inspiratory muscle activity during NREM sleep.

We investigated the effect of acute and sustained inspiratory resistive loading (IRL) on the activity of expiratory abdominal muscles (EMGab) and the diaphragm (EMGdi) and on ventilation during wakefulness and non-rapid-eye-movement (NREM) sleep in healthy subjects. EMGdi and EMGab were measured with esophageal and transcutaneous electrodes, respectively. During wakefulness, EMGdi increased in response to acute loading (18 cmH2O.l-1.s) (+23%); this was accompanied by preservation of tidal volume (VT) and minute ventilation (VE). During NREM sleep, no augmentation was noted in EMGdi or EMGab. Inspiratory time (TI) was prolonged (+5%), but this was not sufficient to prevent a decrease in both VT and VE (-21 and -20%, respectively). During sustained loading (12 cmH2O.l-1 s) in NREM sleep, control breaths (C) were compared with the steady-state loaded breaths (SS) defined by breaths 41-50. Steady-state IRL was associated with augmentation of EMGdi (12%) and EMGab (50%). VT returned to control levels, expiratory time shortened, and breathing frequency increased. The net result was the increase in VE above control levels (+5%, P less than 0.01). No change was noted in end-tidal CO2 or O2. We concluded that 1) wakefulness is a prerequisite for immediate load compensation (in its absence, TI prolongation is the only compensatory response) and 2) during sustained IRL, the augmentation of EMGdi and EMGab can lead to complete ventilatory recovery without measurable changes in chemical stimuli.

Abdominal Muscles↗

PubMed1990

Positional changes in gas exchange after unilateral pulmonary embolism.

We describe positional changes in oxygenation in two patients with respiratory failure due to massive pulmonary embolism. In both patients, oxygenation improved when the "sick" lung was dependent and deteriorated when the "healthy" lung was in the dependent position. These positional changes are different from previously reported changes in unilateral pulmonary disease. We speculate that a combination of unilateral pulmonary embolism and mechanical ventilation was responsible for the improvement in gas exchange when the "sick" lung was placed in the dependent position. The relative contribution of these two components to the development of this phenomenon is unclear.

Aged↗

PubMedDate not supplied

Pathogenesis of obstructive sleep apnea.

Obstructive sleep apnea is a fairly common disorder with significant adverse health consequences. However, the pathogenetic mechanisms remain incompletely understood. Upper airway (UA) patency is determined by several neuromuscular and nonneuromuscular factors including (1) UA dilating muscle activity, (2) the collapsing transmural pressure generated during inspiration, (3) changes in caudal traction, (4) vasomotor tone, and (5) mucosal adhesive forces. This review addresses the effect of sleep on UA function and how these factors conspire to cause UA obstruction.

Humans↗