Biomedical subjects

R L Horner

Publications and source records attributed to R L Horner.

At least 37 records · Page 2Linked to original sources

PubMed1997

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.

Animals↗

PubMed1997

Effect of obstructive sleep apnea versus sleep fragmentation on responses to airway occlusion.

Although the acute physiologic responses to apnea in patients with obstructive sleep apnea (OSA) have been well documented, the changes in these responses over the course of the disease have not been investigated. The purpose of this study was to use a canine model of OSA to examine the long-term effects of sleep apnea on the acute responses to airway occlusion during sleep. Four dogs were studied during a control period before induction of OSA, during a period of OSA (83-133 d), and following cessation of OSA. At least 6 mo after completion of the OSA protocol, the dogs were re-studied on a sleep fragmentation protocol (30-60 d) to determine the impact of a similar degree of sleep disruption, without OSA, on the acute responses to airway occlusion. OSA and sleep fragmentation both resulted in lengthening of the time to arousal in response to acute airway occlusion (p < 0.02) and in greater arterial oxygen desaturation (p < 0.05), peak inspiratory pressures (p < 0.003), and surges in maximum systolic and diastolic blood pressure during airway occlusion (p < 0.01). There were no differences between the changes observed during OSA and during sleep fragmentation. We conclude that the changes in the acute responses to airway occlusion resulting from OSA are primarily the result of the associated sleep fragmentation.

Airway Obstruction↗

PubMed1997

Ventilatory and arousal responses to hypoxia and hypercapnia in a canine model of obstructive sleep apnea.

We have previously described a canine model of obstructive sleep apnea (OSA) in which sleep-wake state is monitored continuously by a computer that produces tracheal occlusion when sleep occurs. Our aim was to assess the effects of long-term application of this model on resting ventilation and on the ventilatory and arousal responses to hypercapnia and hypoxia. Five dogs were maintained on the model for 15.5 +/- 1.7 (mean +/- SE) wk, with a mean apnea index of 57.5 +/- 4.5 occlusions/h of sleep. Resting ventilation and the ventilatory and arousal responses to progressive hypoxic and hypercapnic rebreathing were assessed during wakefulness (W) and both slow-wave (SWS) and rapid-eye-movement (REM) sleep at baseline prior to intervention, at the end of the OSA phase, and following a 1 to 3-mo recovery period. During the period of OSA there were small changes in respiratory timing at rest, but no significant changes in PCO2 or SaO2. As compared with baseline, the ventilatory response to hypoxia during OSA was strikingly reduced during W, and significantly although less markedly reduced during SWS and REM. The reduction was due to a decreased breathing frequency response to hypoxia. In addition, during OSA there was a significant decrease from baseline in SaO2 at arousal during hypoxic rebreathing in both SWS and REM. All responses returned to normal during recovery. In contrast to hypoxia, hypercapnic ventilatory responses during OSA were slightly increased over their baseline values both in W and SWS, owing to a leftward shift of the ventilation-versus-PCO2 relationship. During recovery, these responses reverted partly to baseline for W and reverted completely to baseline for SWS. There were no significant changes in arousal PCO2 during hypercapnic rebreathing in either SWS or REM across the pre-OSA baseline, OSA, and post-OSA recovery periods. We conclude that long-term application of the OSA model is associated with a selective, reversible decrease in ventilatory and arousal responses to hypoxia.

Animals↗

PubMed1996

Motor control of the pharyngeal musculature and implications for the pathogenesis of obstructive sleep apnea.

Obstructive sleep apnea is a common breathing problem that results in recurrent episodes of nighttime hypoxemia, hypercapnia, bradytachycardia, and hypertension, as well as sleep disturbance and daytime hypersomnolence. The obstruction is located in the oropharynx and is caused by hypotonia of the pharyngeal dilator muscles. In this paper, the various mechanisms affecting motor output to the upper airway muscles are reviewed. In particular, the respiratory function of the pharyngeal dilator muscles, the various reflex mechanisms underlying their control, and the effects of sleep on these mechanisms are discussed. The literature relevant to the central neuronal circuits and neurotransmitters that may be involved in the state-dependent activity of the pharyngeal dilator muscles is also reviewed. In addition to an examination of these basic mechanisms, consideration is given throughout this review as to how these mechanisms may relate to the normal control of pharyngeal patency awake and asleep and how they may be involved in the pathogenesis of obstructive sleep apnea.

Carbachol↗

PubMed1996

Autonomic consequences of arousal from sleep: mechanisms and implications.

Normal spontaneous arousals from sleep are associated with transient increases in blood pressure, heart rate, and ventilation caused by large transient changes in autonomic output. These autonomic changes are out of proportion to obvious physiological need and are in excess of those observed in later periods of quiet wakefulness. This paper discusses some of the mechanisms underlying the cardio-respiratory consequences of arousal from sleep, and discusses why the normal onset of wakefulness may be associated with such large changes in autonomic output.

Arousal↗

PubMed1996

Validation of a telemetry system for long-term measurement of blood pressure.

We have used an implanted telemetry system to continuously monitor blood pressure (BP) in three dogs for durations ranging from 28 to 75 wk after implantation. Measurements of BP obtained by telemetry were compared every 3-12 wk, with measurements of BP recorded with a manometer-tipped catheter that was inserted into a femoral artery. Over a wide range of both physiological and pharmacologically manipulated pressures (40-200 mmHg), the values of BP obtained by the two methods were highly correlated (all r > 0.966; all P < or = 0.0001). However, the mean differences between the values obtained by the two systems were different from zero (range +29.6 to -1.5 mmHg; P < or = 0.0001), indicating an offset in the BP values recorded from the implanted system. Furthermore, this offset was dependent on the absolute level of the BP. The findings indicate that, for a period of at least 28 wk and up to 75 wk after implantation, the telemetry system accurately measures acute changes in BP and can reliably measure absolute BP provided that the system is properly validated.

Animals↗

PubMed1995

Respiratory-related heart rate variability persists during central apnea in dogs: mechanisms and implications.

The aim of this study was to determine the mechanism(s) responsible for the persistence of respiratory sinus arrhythmia (RSA) during central apnea. In five awake dogs, heart rate (HR) was recorded during constant mechanical ventilation (MV) and during central apneas produced by cessation of MV. For each of 10 control ventilator cycles before MV was stopped, instantaneous HR was plotted against the time from the onset of lung inflation; the fundamental and first harmonic of a sine wave (at the ventilator frequency) was then fitted to the HR data. For the control cycles, the mean r2 from the curve fits was 0.57 +/- 0.07, showing that a significant component of the HR variability was linked to the ventilator cycle. After MV was stopped, RSA persisted and only by the third "phantom" ventilator cycle during apnea had the degree of fit consistently decreased compared with control dogs (P < 0.02). The persistence of ventilator-linked RSA at the onset of central apnea supports the concept of a "memory" in the respiratory system. Toward the end of central apnea, HR variability reappeared and had the periodicity and rhythmic profile of RSA on 81% of occasions. The presence of RSA-like activity toward the end of central apnea suggests that subthreshold rhythmic respiratory-related activity may be present even before the onset of detectable lung volume changes.

Animals↗

PubMed1995

Immediate effects of arousal from sleep on cardiac autonomic outflow in the absence of breathing in dogs.

To determine the immediate effects of arousal from non-rapid-eye-movement (non-REM) sleep on cardiac sympathetic and parasympathetic activities, six dogs were studied breathing through an endotracheal tube inserted into a chronic tracheostomy. Mean heart rates (HRs) during non-REM sleep were compared with 1) awake periods immediately after spontaneous arousals (ARs) and 2) later periods of stable relaxed wakefulness (RW). During spontaneous breathing, HR increased after AR (mean = 31.0%; P < 0.001) and in RW (mean = 7.6%; P < 0.001). To avoid the confounding influence of changes in breathing pattern, lung volume, and blood gases accompanying AR on HR, further studies were performed during constant mechanical hyperventilation that eliminated spontaneous breathing. In this condition, HR still increased after AR (mean = 29.9%; P < 0.001) and in RW (mean = 5.7%; P < 0.001), suggesting that the HR increases could be mediated by an effect of the state change per se on autonomic activity. This interpretation was confirmed when the HR increases were essentially abolished by combined cardiac sympathetic and parasympathetic block. In contrast, parasympathetic block alone did not prevent the HR increases after AR (mean = 12.2%; P < 0.001) or in RW (mean = 12.3%; P < 0.001), whereas sympathetic block alone almost abolished the HR increases in RW (mean = 3.6%) but did not prevent the HR increases during AR (mean = 30.2%; P < 0.001). The results show that, compared with non-REM sleep, AR is associated with acute cardiac sympathetic activation and parasympathetic withdrawal, whereas stable RW is associated mainly with sympathetic activation. These effects may have clinical relevance to the cardiovascular sequelae of breathing disorders that cause repetitive arousals from sleep.

Animals↗

PubMed1994

The effect of sleep on reflex genioglossus muscle activation by stimuli of negative airway pressure in humans.

The present study was designed to determine the effect of sleep on reflex pharyngeal dilator muscle activation by stimuli of negative airway pressure in human subjects. Intra-oral bipolar surface electrodes were used to record genioglossus electromyogram (EMG) responses to 500 ms duration pressure stimuli of 0 and -25 cmH2O applied, via a face-mask, in four normal subjects. Stimuli were applied during early inspiration in wakefulness and in periods of non-rapid-eye-movement (non-REM) sleep, defined by electroencephalographic (EEG) criteria. The rectified and integrated EMG responses to repeated interventions were bin averaged for the 0 and -25 cmH2O stimuli applied in wakefulness and sleep. Response latency was defined as the time when the EMG activity significantly increased above prestimulus levels. Response magnitude was quantified as the in ratio of the EMG activity for an 80 ms post-stimulus period to an 80 ms prestimulus period; data from after the subject's voluntary reaction time for tongue protrusion (range, 150-230 ms) were not analysed. Application of the -25 cmH2O stimuli caused genioglossus muscle activation in wakefulness and sleep, but in all subjects response magnitude was reduced in sleep (mean decrease, 61%; range, 52-82%; P = 0.011, Student's paired t test). In addition, response latency was increased in sleep in each subject (mean latency awake, 38 ms; range, 30-50 ms; mean latency asleep, 75 ms; range, 40-110 ms; P = 0.072, Student's paired t test). Application of the -25 cmH2O stimuli caused arousal from sleep on 90% occasions, but in all cases the reflex genioglossus muscle responses (maximum latency, 110 ms) always proceeded any sign of EEG arousal (mean time to arousal, 643 ms; range, 424-760 ms). These results show that non-REM sleep attenuates reflex genioglossus muscle activation by stimuli of negative airway pressure. Attenuation of this reflex by sleep may impair the ability of the upper airway to defend itself from suction collapse by negative pressures generated during inspiration; this may have implications for the pathogenesis of obstructive sleep apnoea.

Adult↗

PubMed1994

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.

Animals↗

PubMed1994

Tonic respiratory drive in the absence of rhythm generation in the conscious dog.

This study was designed to determine whether a chemoreceptor-mediated tonic respiratory drive exists below the apneic threshold. Expiratory (triangularis sterni) and inspiratory (diaphragm and parasternal intercostal) electromyographic activities were recorded in three awake relaxed dogs breathing through an endotracheal tube inserted into a permanent tracheostomy. The cervical vagus nerves were cold blocked to avoid the complicating effects of vagal inputs on respiratory activity. During hypocapnia produced by mechanical hyperventilation, expiratory muscle activity converted from rhythmic to tonic discharge when inspiratory muscle activity and spontaneous breathing movements were abolished. In hypocapnia, changes in arterial PCO2 (in hyperoxia) were produced by changing the ventilator rate for steady-state (> 6 min) CO2 stimuli and by disconnecting the ventilator for transient CO2 stimuli. By use of either method, a CO2-mediated drive to the expiratory muscle was consistently observed during hypocapnic apnea. At a constant level of hypocapnia, inhalation of 5% O2 consistently caused the onset of spontaneous breathing; the onset of phasic inspiratory activity was associated with reciprocal inhibition of the tonic expiratory activity. However, inhalation of 10 and 15% O2 caused an inhibition of the tonic expiratory activity, even without the onset of breathing. These results suggest that the response threshold of the respiratory chemoreceptors is lower than the apneic threshold and that a chemoreceptor-mediated tonic respiratory drive persists during apnea.

Animals↗

PubMed1994

Canine model of obstructive sleep apnea: model description and preliminary application.

This report describes a canine model of obstructive sleep apnea (OSA) developed in our laboratory and the results of its preliminary short-term application. Healthy adult dogs were prepared with a tracheostomy and with implanted electroencephalographic and nuchal electromyographic recording electrodes. A silent occlusion valve was attached to the outer end of the endotracheal tube. The electroencephalogram and electromyogram were monitored continuously by a computer that determined sleep-wake state using software developed in our laboratory. At a predetermined time (e.g., 12 s) after each sleep onset, a signal was transmitted from the computer to the valve controller, resulting in airway occlusion. When the dog aroused from sleep, the occlusion was released. These events therefore mimic those that occur in human OSA. Successful operation of the model was confirmed during 5-day continuous trials in two dogs. During the trials, the dogs became increasingly somnolent both by behavioral observation and objective measurement. The frequency of occlusions increased, and measures of apnea severity, including apnea duration and end-apneic arterial oxygen saturation, worsened. We conclude that this experimental model of repeated airway occlusion during sleep provides a potentially powerful tool for investigating the sequelae of OSA.

Airway Obstruction↗

PubMed1993

Reflex pharyngeal dilator muscle activation by stimuli of negative airway pressure in awake man.

This paper summarizes evidence for reflex genioglossus muscle activation by stimuli of negative airway pressure in normal, awake human subjects. Stimuli of negative airway pressure (range -5 to -35 cm H2O) caused activation of the genioglossus muscle. The larger values of negative pressure gave larger responses. Response latencies (median = 34 milliseconds) were much faster than the time for voluntary muscle activation (median = 184 milliseconds), suggesting that the responses were reflex in origin. The reflex nature of the responses was confirmed by studies with local anesthetics. The trigeminal, superior laryngeal and the glossopharyngeal nerves all mediated a component of the responses observed from the upper airway.

Air Pressure↗

PubMed1991

Volume detection during voluntary and passive breathing.

The ability to detect small changes in tidal volume (VT) during either volitional or passive breathing was compared in seven normal subjects. Passive breathing was achieved with positive pressure applied at the mouth by a ventilator. Although baseline breathing pattern was similar for each subject during the two types of breathing, the ability of the subjects to detect changes in VT was at least as good, and in general better, during passive as compared to volitional breathing. This suggests that the generation of a motor cortical command to inspire and the resultant respiratory muscle contraction are not essential to the perception of a change in lung volume. An increase in information from receptors in the mouth, pharynx and extrathoracic airways sensitive to positive pressure may be responsible for the increased ability of most subjects to detect changes in VT during passive breathing.

Adult↗

PubMed1991

Some factors affecting the maintenance of upper airway patency in man.

This paper describes some of the anatomical and physiological factors affecting the maintenance of upper airway patency in man. Such factors have particular relevance to the mechanisms responsible for maintaining upper airway patency during sleep, and the failure of these mechanisms in patients with the clinical syndrome of obstructive sleep apnoea: a condition in which repeated episodes of sleep-related inspiratory oropharyngeal collapse lead to recurrent hypoxaemia, disturbed sleep patterns and other clinical sequelae. The relationships between upper airway geometry, negative intrapharyngeal pressure, activation of upper airway dilator muscles, and sleep state are important factors affecting the maintenance of upper airway patency. The aim of this paper is not to consider such factors in isolation but to consider their interaction in affecting the adequacy of the upper airspace as a conduit for airflow.

Humans↗

PubMed1991

Evidence for reflex upper airway dilator muscle activation by sudden negative airway pressure in man.

1. To determine if negative upper airway pressure causes reflex pharyngeal dilator muscle activation, we used intra-oral bipolar surface electrodes to record genioglossus electromyogram (EMG) activity in response to 500 ms duration pressure stimuli of 0, -2.5, -5, -15, -25 and -35 cm H2O (0-90% rise time less than 30 ms) in ten normal, conscious, supine subjects. 2. With the subjects relaxed at end-expiration, stimuli were applied in each of three conditions: (i) glottis open (GO), (ii) glottis closed (GC) and (iii) controls with the mouth and nose closed. 3. Six rectified and integrated EMG responses were bin averaged for each pressure in each experimental condition. Response latency was defined as the time when the EMG activity significantly increased above pre-stimulus levels. Response magnitude was quantified as the ratio of the EMG activity for 80 ms post-stimulus to 80 ms prestimulus; data from after the subject's voluntary reaction time (for tongue protrusion) were not analysed. 4. Negative airway pressure activated the genioglossus. The median latency of activation (34 ms) was much faster than the time for voluntary activation (184 ms) indicating a reflex response. 5. Significant activation, compared to 0 cmH2O controls and controls with mouth and nose closed, occurred with pressures of at least -5 cm H2O (GC) and -15 cm H2O (GO). At -25 and -35 cm H2O, responses with GO were significantly greater than with GC. 6. The magnitude ('strength') of the responses differed between subjects; these differences were repeatable. 7. We conclude that negative airway pressure causes reflex pharyngeal dilator muscle activation in man. Responses with GC suggest that upper airway receptors can mediate the response but larger responses with GO indicate a contribution from subglottal receptors.

Adult↗

PubMed1991

Afferent pathway(s) for pharyngeal dilator reflex to negative pressure in man: a study using upper airway anaesthesia.

1. To determine the afferent pathways mediating pharyngeal dilator muscle activation in response to negative airway pressure in man, we recorded genioglossus electromyogram (EMG) activity (via intra-oral bipolar surface electrodes) in response to 500 ms duration pressure stimuli of -15 and -25 cm H2O in normal, conscious, supine subjects relaxed at end-expiration; responses were compared before and after upper airway anaesthesia. 2. Six rectified and integrated EMG responses were bin averaged for pressure stimuli applied with the glottis open (GO) and closed (GC) and to the outside of the face only (controls). Response magnitude was quantified as the ratio of the EMG activity for an 80 ms post-stimulus period (before the subject's reaction time for tongue protrusion) to an 80 ms pre-stimulus period. 3. In eight subjects, upper airway anaesthesia reduced the EMG responses with GC to a level indistinguishable from controls. After anaesthesia, responses with GO remained higher than those with GC. 4. With GC, the mean EMG responses decreased by 43% after selective anaesthesia of the nasal mucosa (trigeminal nerves) in two subjects, 32% after selective anaesthesia of the laryngeal mucosa (superior laryngeal nerves) in six subjects and by 21% after selective anaesthesia of the oropharyngeal mucosa (glossopharyngeal and lingual nerves) in four subjects. 5. We conclude that upper airway afferents mediate pharyngeal dilator muscle activation in response to negative pressure with GC and that subglottal receptors caused the increased activation with GO. With GC, the trigeminal and superior laryngeal nerves mediate an important component of the responses with the glossopharyngeal nerves playing a less important role.

Adult↗

PubMed1991

The influence of induced hypocapnia and sleep on the endogenous respiratory rhythm in humans.

1. Ventilation has been studied during hypocapnia produced by passive mechanical ventilation in ten normal human subjects. 2. During wakefulness, disconnection of the ventilator led to inconsistent apnoea of only brief duration. During sleep, at a similar degree of hypocapnia, disconnection of the ventilator led more consistently to apnoea which was also of much longer duration; the deeper the sleep stage, the longer the apnoea. 3. The resumption of breathing during sleep could precede or follow arousal or be unaccompanied by arousal; in the absence of prior arousal, the evidence suggests that a starting end-tidal CO2 pressure (PET, CO2) less than 41 mmHg could result in an apnoea during sleep stages I and II. 4. Subjects did not report any common sensation which led them to breathe following an apnoea whilst awake. 5. Prior hyperoxia in one subject prolonged the apnoea duration in both slow-wave sleep and rapid eye movement sleep. 6. The results are interpreted as showing that even during light sleep, the maintenance of the respiratory rhythm is critically dependent on the arterial CO2 and O2 tensions. During wakefulness, other behavioural drives, which may not reach consciousness, supervene.

Adult↗