Louise F. Kozar

Obstructive sleep apnea as a cause of systemic hypertension. Evidence from a canine model.

Several epidemiological studies have identified obstructive sleep apnea (OSA) as a risk factor for systemic hypertension, but a direct etiologic link between the two disorders has not been established definitively. Furthermore, the specific physiological mechanisms underlying the association between OSA and systemic hypertension have not been identified. The purpose of this study was to systematically examine the effects of OSA on daytime and nighttime blood pressure (BP). We induced OSA in four dogs by intermittent airway occlusion during nocturnal sleep. Daytime and nighttime BP were measured before, during, and after a 1-3-mo long period of OSA. OSA resulted in acute transient increases in nighttime BP to a maximum of 13.0+/-2.0 mmHg (mean+/-SEM), and eventually produced sustained daytime hypertension to a maximum of 15.7+/-4.3 mmHg. In a subsequent protocol, recurrent arousal from sleep without airway occlusion did not result in daytime hypertension. The demonstration that OSA can lead to the development of sustained hypertension has considerable importance, given the high prevalence of both disorders in the population.

The ventilatory response to arousal from sleep is not fully explained by differences in CO2 levels between sleep and wakefulness

1 Arousal from sleep is associated with transient stimulation of ventilation above normal waking levels that predisposes to subsequent breathing instability and central apnoea. The transient hyperpnoea at arousal is normally explained by differences in arterial partial pressure of CO2 (P  a,CO 2) between sleep and wakefulness, with a higher P  a,CO 2 in sleep leading to stimulation of ventilation at arousal according to the awake ventilatory response to CO2. Surprisingly, however, the validity of this current model in fully explaining the increased ventilation at arousal from sleep has not been directly tested. 2 This study tests the hypothesis that the level of ventilation at arousal from non‐rapid eye movement (non‐REM) sleep is greater than that produced by elevating P  a,CO 2 in wakefulness to the sleeping level, i.e. the ventilation predicted by the current model. 3 Studies were performed in five dogs. Inspired CO2 was used to increase end‐tidal partial pressure of CO2 (P  ET,CO 2) in wakefulness and measure the ventilatory response. The same P  ET,CO 2 was then maintained in non‐REM sleep. Ventilation was measured for 10 breaths before and after arousal from non‐REM sleep induced by a 72 dB tone. 4 Arousal from sleep produced a transient surge in ventilation of 1.42 ± 0.35 l min−1 (P= 0.005). This increased ventilation was due to arousal from sleep per se as the tone alone produced no change in awake ventilation. In support of the hypothesis, ventilation at wake onset from sleep was greater by 0.83 ± 0.28 l min−1 (P= 0.031) than the ventilation elicited in wakefulness by raising P  ET,CO 2 to the sleeping level. 5 The results show that > 50% of the increase in ventilation at wake onset from sleep is not attributable to the awake ventilatory response to the elevated P  a,CO 2 that was previously present in sleep. This result leads to important modifications of the physiological model currently used to explain the ventilatory consequences of arousal from sleep.

Effects of sleep on the tonic drive to respiratory muscle and the threshold for rhythm generation in the dog.

1. The present study was designed to determine the effect of sleep on the tonic output to respiratory muscle and on the level of chemical respiratory stimulation required to produce rhythmic respiratory output. 2. Chronically implanted electrodes recorded expiratory (triangularis sterni) and inspiratory (diaphragm and parasternal intercostal) electromyographic (EMG) activities in three trained dogs during wakefulness and sleep. The dogs were mechanically hyperventilated via an endotracheal tube inserted into a permanent tracheostomy. During the studies, a cold block of the cervical vagus nerves was maintained to avoid the complicating effects of vagal inputs on respiratory drive and rhythm. 3. During wakefulness, steady‐state hypocapnia (partial pressure of CO2, PCO2 = 30 mmHg) abolished inspiratory EMG activity, resulting in apnoea, but the expiratory muscle became tonically active. Compared to wakefulness, the level of the tonic expiratory EMG activity was decreased in non‐REM (non‐rapid eye movement) sleep (median decrease = 34%, P = 0.005) and was further decreased in REM sleep (median decrease = 78%, P < 0.0001). During REM sleep, the tonic expiratory EMG activity was highly variable (mean coefficient of variation = 39% compared to 7% awake, P < 0.0001) and in some periods of REM, bursts of inspiratory EMG activity and active breathing movements were observed despite the presence of hypocapnia. 4. During constant mechanical hyperventilation, progressive increases in arterial PCO2 (in hyperoxia) were produced by rebreathing. Measurement of the CO2 threshold for the onset of spontaneous breathing showed that this threshold was not different between wakefulness and non‐REM sleep (mean difference = 0.1 mmHg from paired observations, 95% confidence interval for the difference = ‐1.0 to +1.1 mmHg, P = 0.898). 5. The results show that sleep reduces the tonic output to respiratory muscles but does not increase the CO2 threshold for the generation of rhythmic respiratory output. These observations suggest that changes in the tonic drives to the respiratory motoneurones may be a principal mechanism by which changes in sleep‐wake states produce changes in respiratory output.

Respiratory activity of laryngeal muscles in awake and sleeping dogs

Experiments were conducted in adult dogs to determine the respiratory activity of laryngeal muscles during wakefulness and sleep. We studied the EMG activity of three laryngeal muscles in five trained dogs, two of which were completely intact, and three of which had a previously-formed side-hole tracheal stoma. Pairs of electrodes were implanted chronically into the posterior cricoarytenoid muscle (PCA), a laryngeal dilator, cricothyroid (CT), and thyroarytenoid (TA), a laryngeal adductor. EMG electrodes were also inserted into the costal portion of the diaphragm. In wakefulness (W), slow wave sleep (SWS) and rapid eye movement (REM) sleep the EMGs of the PCA and CT muscles increased in intensity during diaphragm activation, with varying levels of basal activity during expiration. However, the greatest levels of inspiratory activity in PCA and CT during sleep were found in REM sleep, usually in the absence of augmented diaphragm EMG activity. This laryngeal muscle activity was associated with laryngeal dilation. There were also marked state-related changes in the level of activity of CT during expiration, suggestive of changes in the degree of expiratory adduction of the larynx. The adductor muscles (TA) were not active during expiration, except during alert W. There were no consistent differences in respiratory activity of the laryngeal muscles between the two intact dogs and those with a tracheal stoma (whether or not an endotracheal tube was in place), nor was laryngeal muscle activity affected by the subsequent creation of a tracheal stoma in the two intact dogs. The findings indicate that sleep-wakefulness state exerts important influences on the respiratory activity of laryngeal muscles in the adult dog.

The flutter device and expiratory pressures.

PURPOSE Flutter therapy uses a handheld instrument that consists of a pipe-like device with a ball in the central core that oscillates during exhalation, providing oscillating positive expiratory pressure. The purpose of this study was to determine the effect of airflow and the incline of the device at the mouth on expiratory pressure and oscillation frequency. METHODS A Flutter device was attached to a circuit that consisted of a pneumotachograph and a ventilator. The ventilator generated different flows and expiratory pressure was measured with a pressure transducer. The angles considered were +40 degrees to -40 degrees in increments of 10 degrees , with the reference for incline being the horizontal line. Expiratory pressure, airflow, angle of incline, and oscillation frequency were measured. RESULTS There was a strong and significant correlation between flow and expiratory pressure at each level of incline (P < or =006; r > 0.93). There also was a significant and strong correlation between expiratory pressure and oscillation frequency (P <.05; r = 0.81-0.97). There was a significant reduction in expiratory pressure at a negative incline of -40 degrees. CONCLUSIONS The results of this study indicate that a positive incline and a large airflow result in an increase in expiratory pressure. This information will assist clinicians to better understand the effects of the Flutter device.