Biomedical subjects

S A Shea

Publications and source records attributed to S A Shea.

At least 37 records · Page 2Linked to original sources

PubMed2000

Acute changes in carbon dioxide levels alter the electroencephalogram without affecting cognitive function.

The partial pressure of carbon dioxide in the arterial blood (PaCO2) is usually tightly regulated, yet it varies among healthy people at rest (range approximately 32-44 mmHg) as well as within an individual during many natural life situations. The present study examined whether modest changes in end-tidal PCO2 (PETCO2; a noninvasive measure of PaCO2) affect electroencephalographic (EEG) activity, cognitive function, and vigilance. Nine adults were ventilated mechanically using a mouthpiece; respiratory rate and breath size were held constant while PETCO2 was set to levels that produced minimal discomfort. Despite discrete changes in EEG, neither acute PETCO2 increases (mean = 47 mmHg) nor decreases (mean = 30 mmHg) from resting levels (mean = 38 mmHg) affected performance on cognitive tasks, latency or amplitude of the N1, P2, or P3 event-related potential, or alertness. Modest changes in PETCO2 may cause significant alterations in the EEG without disturbing cognitive function.

Adult↗

PubMed2000

Endogenous circadian control of the human autonomic nervous system.

To determine if an endogenous circadian rhythmicity, independent from sleep/wake cycles, exists in autonomic nervous system (ANS) function, heart rate variability analysis of electrocardiogram R-R intervals was applied to data collected during a 27-day forced desynchrony protocol. Results during wakefulness indicate that the circadian pacemaker may control both the sympathetic and vagal limbs of the ANS. Vagal tone was maximal during the circadian phase corresponding to the usual sleep episode (although these measurements were made in the absence of sleep) with an acrophase at 4 AM to 5 AM. Sympathovagal balance was minimal between 9 AM and 1 PM. These endogenous circadian rhythms in ANS function may contribute to mortality from cardiovascular disease and nocturnal asthma.

Adult↗

PubMed1999

Effect of wake-sleep transitions and rapid eye movement sleep on pharyngeal muscle response to negative pressure in humans.

1. Genioglossus (GG) activation in response to upper airway negative pressure may be an important mechanism in the maintenance of airway patency. This reflex occurs during wakefulness but is diminished during stable non-rapid eye movement (NREM) sleep. Since obstructive events occur more commonly at wake-sleep transitions and during rapid eye movement (REM) sleep than during stable NREM sleep, we assessed the GG reflex during these two vulnerable states. 2. Seventeen healthy adults were studied throughout one evening and overnight. Electroencephalograms (EEGs), electro-oculograms (EOGs), submental electromyogram (EMG), GG EMG (intramuscular electrodes), and choanal plus epiglottic pressures were recorded. The GG reflex response to pulses of -8 cmH2O choanal pressure applied via nose mask during early inspiration was quantified repeatedly during relaxed wakefulness, within five breaths of wake-sleep transition (EEG alpha-theta transition) and during REM sleep. Only trials without EEG arousal were analysed, resulting in data from 14 subjects during sleep onset and 10 subjects during REM sleep (overall, 174-491 trials per state). 3. During wakefulness there was brisk GG reflex activation in response to negative pressure (amplitude: +78.5 +/- 28.3 % baseline (mean +/- s.e.m.); latency to maximal response: 177 +/- 16 ms). 4. At sleep onset, although there was marked variability among individuals, there was no significant reduction in the magnitude of the GG reflex for the group as a whole (amplitude: +33.2 +/- 8.2 % baseline; latency: 159 +/- 15 ms). 5. In contrast, during REM sleep there was a reduction of GG reflex (amplitude: -12.6 +/- 8.3 % baseline (P = 0.017 vs. awake); latency: 160 +/- 10 ms (n.s. vs. awake)) and greater airway collapsibility during the applied pressures (P = 0.043 vs. awake). 6. We conclude that there was no systematic reduction in the GG reflex to negative pressure at sleep onset. Nonetheless, it remains possible that sleep-deprived normal subjects and patients with sleep apnoea could react differently. 7. The apparent inhibition of the GG reflex during REM sleep may help explain why the upper airway is vulnerable to collapse during this state.

Adult↗

PubMed1999

Functional MRI localisation of central nervous system regions associated with volitional inspiration in humans.

1. Functional magnetic resonance imaging (fMRI) provides a means of studying neuronal circuits that control respiratory muscles in humans with better spatial and temporal resolution than in previous positron emission tomography (PET) studies. 2. Whole brain blood oxygenation level-dependent (BOLD) changes determined by fMRI were used to identify areas of neuronal activation associated with volitional inspiration in five healthy men. Four series of scans of each subject were acquired during voluntary breathing (active task) and mechanical ventilation (passive task). Ventilation and end-tidal PCO2 were similar between tasks. Scan data were re-aligned to correct for movement artefacts and cross-referenced breath by breath to respiratory data for selective averaging of inspiratory and expiratory images. 3. Group analysis identified significant increases in the fMRI signal with volitional inspiration in the superior motor cortex, premotor cortex and supplementary motor area at loci similar to those detected in earlier studies that used PET. Additional regions activated by volitional inspiration included inferolateral sensorimotor cortex, prefrontal cortex and striatum (these foci were only revealed by PET under significant inspiratory load). 4. This study represents the first synchronised breath-by-breath analysis of respiratory-related neuronal activity with whole brain imaging in humans. Temporal resolution is sufficient to distinguish individual breaths at a normal breathing frequency.

Adult↗

PubMed1999

Cardiorespiratory variables and sensation during stimulation of the left vagus in patients with epilepsy.

We studied physiological and sensory effects of left cervical vagal stimulation in six adult patients receiving this stimulation as adjunctive therapy for intractable epilepsy. Stimulus strength varied among subjects from 0.1 to 2.1 microCoulomb (microC) per pulse, delivered in trains of 30-45 s at frequencies from 20 to 30 Hz; these stimulation parameters were standard in a North American study. The stimulation produced no systematic changes in ECG, arterial pressure, breathing frequency tidal volume or end-expiratory volume. Five subjects experienced hoarseness during stimulation. Three subjects with high stimulus strength (0.9-2.1 microC) recalled shortness of breath during stimulation when exercising; these sensations were seldom present during stimulation at rest. No subjects reported the thoracic burning sensation or cough previously reported with chemical stimulation of pulmonary C fibers. Four of six subjects (all those receiving stimuli at or above 0.6 microC) experienced a substantial reduction in monthly seizure occurrence at the settings used in our studies. Although animal models of epilepsy suggest that C fibers are the most important fibers mediating the anti-seizure effect of vagal stimulation, our present findings suggest that the therapeutic stimulus activated A fibers (evidenced by laryngeal effects) but was not strong enough to activate B or C fibers.

Adult↗

PubMed1998

Local reflex mechanisms: influence on basal genioglossal muscle activation in normal subjects.

STUDY OBJECTIVES: To define the influence of topical nasopharyngeal anesthesia on genioglossal EMG responsiveness to both negative pressure and basal muscle activity. The effects on airway mechanics (resistance and collapsibility) were also determined. PARTICIPANTS: 18 normal adult subjects (9 males and 9 premenopausal females) DESIGN AND MEASUREMENTS: Genioglossal EMG (GG EMG) was measured with intramuscular electrodes. Basal phasic and tonic GG EMG were defined, in addition to the muscle response to multiple brief applications of negative airway pressure (-10 to 12 cm H2O). Airflow resistance (at 0.2 L/second and peak flow) plus airway collapsibility were also determined. All measurements were completed with and without dense nasopharyngeal anesthesia (lidocaine). RESULTS: Following nasopharyngeal anesthesia, peak GG EMG response to negative pressure fell from 28.1+/-4.3 (SE) to 19.6+/-3.4% of maximum (p<0.01). This was associated with a significant fall in both peak phasic and tonic GG EMG under basal conditions (phasic: 20.2+/-3.2 to 15.9+/-2.7% of maximum, tonic: 13.9+/-2.5 to 9.8+/-1.8% of maximum). Falling muscle activity led to a trend of rising airflow resistance and increasing airway collapsibility. CONCLUSIONS: Local, topical receptor mechanisms located in the nasopharynx importantly modulate upper airway dilator muscle activity in humans during normal tidal breathing. Therefore, the mechanisms exist for the airway to respond to local events which would tend to compromise airway patency.

Adult↗

PubMed1998

Respiratory sensations during heavy exercise in subjects without respiratory chemosensitivity.

Breathlessness arises from increased medullary respiratory center activity projecting to the forebrain (respiratory corollary discharge hypothesis). Subjects with congenital central hypoventilation syndrome (CCHS) lack the normal hyperpnea and breathlessness during hypercapnia. The corollary discharge hypothesis predicts that if CCHS subjects have normal hyperpnea during exercise, they will experience normal breathlessness during exercise. To test this, we studied four CCHS subjects and six matched controls during an exhausting constant-load cycling test requiring substantial anaerobiosis. CCHS subjects rated significantly less breathlessness at the end of the test than controls, but ventilation (index of respiratory corollary discharge) was also somewhat lower in CCHS (not significant). In both groups, breathlessness increased disproportionately more than ventilation towards the end of exercise. These data failed to disprove the corollary discharge hypothesis of breathlessness, but do suggest that the relationship between ventilation and breathlessness is non-linear and/or that projections of chemoreceptor afferents to the forebrain (presumed lacking in CCHS) is one source of breathlessness in normals.

Adolescent↗

PubMed1998

Competition between gas exchange and speech production in ventilated subjects.

Competition between airflow requirements for speaking and gas exchange occurs in ventilator-dependent tracheotomized subjects who can 'steal' air from alveolar ventilation during the ventilator's inflation phase to produce sound. We wondered whether these subjects adopted strategies to minimize hypoventilation when speaking, particularly when ventilatory drive and respiratory discomfort are increased by hypercapnia. We recorded speech and ventilatory and speaking volumes in five ventilated subjects during reading and extemporaneous speech. All subjects spoke during the ventilator's inflation (and expiratory) phase, losing approximately 15% of their inspired tidal volume. During induced hypercapnia (15 mmHg increase in PetCO2) which caused shortness of breath, all subjects could still speak adequately. Two subjects 'adapted' to hypercapnia by reducing the air used for speaking during inflation. In contrast, one subject reacted, as normal subjects do, by increasing the airflow per syllable (a mal-adaptive strategy in ventilated subjects). These changes were modest despite the strong hypercapnic stimulus.

Adult↗

PubMed1997

Perception of inflation of a single lung lobe in humans.

We tested whether subjects could detect and localize inflation confined to a single lung lobe. A balloon-sealed catheter was placed into a lobar bronchus of unsedated subjects via fiberoptic bronchoscopy. Topical anesthesia (lidocaine) was used to suppress cough and irritation associated with inflation of the sealing balloon. Small (45-60 ml) or large (100-240 ml) stimulus volumes were insufflated via the catheter. In a forced-choice protocol, subjects were readily able to detect large inflations and correctly identify the side on which the stimulus was given, but small inflations were at the threshold of detection and were not correctly localized. Additional lidocaine applied to the bronchus in two subjects did not degrade detection. Circumstantial evidence suggests that the sensation arose in the lung. We conclude that this technique is feasible for the study of pulmonary perception.

Adult↗

PubMed1997

Life without ventilatory chemosensitivity.

In healthy humans ventilatory chemoreception results in exquisite regulation of arterial blood gases during NREM sleep, but during wakefulness other behavioral and arousal-related influences on breathing compete with chemoreceptive respiratory control. This paper examines the extent of chemoreceptive control of breathing within the normal physiological range in awake and sleeping humans and explores the consequences upon breathing of absent chemoreceptive function. Recent studies of subjects with congenital central hypoventilation syndrome (CCHS) demonstrate the extent of behavioral and arousal-related influences on breathing in the absence of arterial blood gas homeostasis. CCHS subjects lack chemoreceptor control of breathing and seriously hypoventilate during NREM sleep, requiring mechanical ventilation. Many CCHS subjects breathe adequately during many waking behaviors associated with arousal, cognitive activity or exercise--presumably reflecting input to the brainstem respiratory complex from the reticular activating system, the forebrain or mechanoreceptor afferents. In most situations, and despite changes in metabolism, the non-chemoreceptive inputs to breathing result in surprisingly well controlled arterial blood gases in CCHS patients.

Chemoreceptor Cells↗

PubMed1996

Stimulus-response characteristics of CO2-induced air hunger in normal subjects.

Hypercapnia evokes an uncomfortable sensation, termed 'air hunger'. We examined the relationship between PETCO2 and ratings of air hunger intensity under three conditions in 16 subjects: 1) mechanical ventilation with hyperoxic gas mixtures at fixed frequency and tidal volume (twice resting ventilation), 2) the same mechanical ventilation, but with hypoxic gas mixture, 3) spontaneous breathing with hyperoxic gas mixture. In each case, PETCO2 was varied randomly among several levels, each held for 5 min. During hyperoxic mechanical ventilation, the mean threshold for air hunger sensation was 43 Torr, i.e., 4 Torr above resting PETCO2; intolerable air hunger was evoked by 50 Torr. The threshold and tolerable levels of PETCO2 varied among individuals, but were not well correlated with their ventilatory responses to CO2. Hypoxia (PETO2 60-75 Torr) shifted the PETCO2 at both threshold and tolerance down by only 2 Torr. Breathing greatly reduced the air hunger experienced at any given PETCO2 (threshold increased 5 Torr, and sensitivity decreased 50%).

Female↗

PubMed1996

Self-control of level of mechanical ventilation to minimize CO2 induced air hunger.

Hypercapnia produces an uncomfortable urge to breathe ('air hunger'), which is alleviated by increasing breathing. It has been postulated that awake humans control breathing partly to minimize these sensations; such behavioral control presumably involves the forebrain. To test this postulate, we compared the ventilatory response to hypercapnia when the subject breathed spontaneously to the response when the subject used forebrain commands to control ventilation--on the basis of minimizing air hunger (achieved with subject-controlled positive pressure ventilation). In six healthy adults during hypercapnia (46 mmHg), spontaneous ventilation significantly exceeded, by 17%, the level of (mechanical) ventilation needed to alleviate air hunger. This suggests that spontaneous breathing is not behaviorally controlled to minimize discomfort. Alternatively, mechanical ventilation confers an additional relief of air hunger beyond that provided by spontaneous breathing. Since mechanical ventilation (with reduced respiratory muscle contraction) was more effective than spontaneous breathing in relieving air hunger, our results also suggest afferents that signal the degree of respiratory muscle contraction do not contribute to air hunger relief.

Adult↗

PubMed1996

Behavioural and arousal-related influences on breathing in humans.

This review has described the many behavioural and arousal-related influences on breathing and the extent of these influences in humans. The chief examples have included the effect on breathing of altered mental activity, wakefulness and sleep, and learned respiratory responses. Determining the precise neurological mechanisms underlying these effects represents a difficult challenge to respiratory physiologists who seek to understand the respiratory control system of awake behaving humans. Nevertheless, insight into the various forebrain and brainstem inputs to respiratory muscles has been gained by studies of breathing during particular behaviours (when either voluntary or reflex breathing predominates) or in particular neurological patients (in whom either voluntary or reflex breathing is defective). With developments in brain imaging techniques, such as functional magnetic resonance imaging, it may soon be possible to determine more precisely the various anatomical sources and timing of the motor commands to breathe during different behaviours, states of arousal and sleep.

Arousal↗

PubMed1996

Air hunger induced by acute increase in PCO2 adapts to chronic elevation of PCO2 in ventilated humans.

Brief increases in arterial PCO2 (PaCO2) (lasting several minutes) produce a sensation of respiratory discomfort (air hunger). It is not known whether air hunger adapts to chronic changes in PaCO2. This study tested whether the level of end-tidal PCO2 (PETCO2) required to evoke air hunger would increase with chronic elevation of PETCO2 (lasting several days). Four ventilator-dependent subjects participated in a 2-wk study during which they were ventilated with air (placebo) or air rich in CO2 (CO2 exposure). Average resting PETCO2 during control periods was 25 Torr (typical for such patients); PETCO2 was 15 Torr higher during CO2 exposure. Ventilation and arterial PO2 did not differ between conditions. Periodically, we performed tests in which subjects rated the intensity of air hunger induced by brief increases in PETCO2. The increase in PETCO2 required to elicit a given air hunger rating during CO2 exposure also increased by approximately 15 Torr. That is, subjects' sensation of air hunger fully adapted to the chronic increase in PETCO2. Arterial pH did not fully return to control values during CO2 exposure. Accommodation in the chemoreceptors and neural pathways that subserve air hunger sensation may explain the adaptation of air hunger.

Adaptation, Physiological↗

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

Speech production during mechanical ventilation in tracheostomized individuals.

This investigation provides the first detailed description of speech production during mechanical ventilation. Seven adults with tracheostomies served as subjects. Recordings were made of chest wall motions, neck muscle activity, tracheal pressure, air flow at the nose and mouth, estimated blood-gas levels, and the acoustic speech signal during performance of a variety of speech tasks. Results indicated that subjects spoke for short durations that spanned all phases of the ventilator cycle, altered laryngeal opposing pressures in response to the continually changing tracheal pressure wave, and expended relatively small volumes of gas for speech production. Speech was improved by making selected ventilator adjustments. Suggestions for clinical interventions are offered.

Adult↗

PubMed1993

Respiratory sensations in subjects who lack a ventilatory response to CO2.

An urge to breath is perceived during breath hold and hypercapnia (termed 'air hunger') and during heavy exercise (often termed 'shortness of breath'). To better understand the neural mechanisms responsible for these sensations we studied five patients (8-17 years old) with congenital central hypoventilation syndrome (CCHS) who lack ventilatory response to CO2. CCHS patients reported no respiratory discomfort during CO2 inhalation or during maximal breath hold which was of much longer duration than age-matched controls. However, all 3 CCHS patients who exercised heavily reported some sensations akin to shortness of breath (they increased breathing nearly as much as controls). Our results are consistent with two possibilities. First, the air hunger of hypercapnia and breath hold is caused by projection to the forebrain of respiratory chemoreceptor afferents which bypass the respiratory centers, while exercise shortness of breath is caused by direct projections of limb afferents or locomotory center activity. Second, air hunger and shortness of breath share the same origin--projection of increased brain stem respiratory center motor activity (corollary discharge) to the forebrain.

Adolescent↗

PubMed1993

Effect of mental activity on breathing in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) is associated with hypoventilation during sleep, but breathing can be adequate during wakefulness. It has been assumed that in awake CCHS patients breathing is activated by the forebrain, even voluntarily (i.e. Ondine's Curse). We tested whether or not an abnormal breathing pattern can be provoked by intense mental concentration in CCHS patients as this would be expected to disturb any voluntary control over breathing if present. Breathing (inductance plethysmography), end-tidal PCO2) (PETCO2), arterial oxygen saturation (SaO2) and EEG were measured in 5 children with CCHS (aged 8-17 years) and 5 controls during 5 min periods while resting; reading; performing mental arithmetic and playing a hand-held "Nintendo" game. There were no significant differences between controls and CCHS (unpaired t-tests, P > 0.05) in mean breath duration, tidal volume, ventilation, SaO2 or PETCO2 during REST or the conditions of mental stimulation. Both groups increased ventilation during mental stimulation. Respiratory variability was not greater in CCHS in any condition. These data provide indirect evidence that CCHS patients do not require voluntary activation of every breath (they do not have Ondine's Curse) and suggest that mental concentration might stimulate the respiratory complex as part of a generalised CNS arousal.

Adolescent↗