Search PubMed⌕ Search

Biomedical subjects

S A Shea

Publications and source records attributed to S A Shea.

At least 55 records · Page 3Linked to original sources

Effects of inspiratory support upon breathing in humans during wakefulness and sleep.

We have compared the effects on breathing of inspiratory mechanical support during wakefulness and sleep in healthy subjects. Nine awake volunteers breathed through a nose mask connected to a machine supplying variable levels of inspiratory positive airway pressure (IPAP). Tidal volume (VT), breath duration (TTOT) and end-tidal PCO2 (PETCO2) were measured over 1 min steady state periods with IPAP set at a minimal level (approx. 2 cmH2O) and at approx. 10 cmH2O. This protocol was repeated in 6 of the subjects during non-REM sleep. When awake, "10 cmH2O IPAP" caused a significant increase in mean VT from 513 to 842 ml and a significant fall in PETCO2 from 39.7 to 32.7 mmHg. During sleep, "10 cmH2O IPAP" caused no significant changes in VT (388 to 390 ml) or PETCO2 (41.8 to 39.8 mmHg). In each state, "10 cmH2O IPAP" had no significant effect on TTOT. Three subjects repeated the protocol with diaphragmatic surface EMG recorded as an index of efferent inspiratory activity. "10 cmH2O IPAP" had no consistent effect on EMG when awake but caused a reduction in each subject during sleep. We conclude that during non-REM sleep, inspiratory mechanical support is associated with a compensatory decrease in efferent inspiratory activity to achieve a similar tidal volume with maintenance of arterial PCO2. When awake, a "wakefulness drive to breathe" may be associated with maintained inspiratory activity such that mechanical support results in an increased tidal volume despite a fall in arterial PCO2.

Adult↗

Breathing patterns of monozygous twins during behavioural tasks.

To better understand behavioural and genetic influences upon breathing, the breathing patterns of 8 pairs of monozygous (MZ) twins were measured under 4 behavioural conditions; relaxed without standardisation; eyes closed; eyes open; and reading. Breathing was quantified by inspiratory and expiratory durations (TI, TE), tidal volume (VT) and derived variables. Airflow shape was normalised and quantified using 8 dimensions. Reading caused breathing to increase by > 500 ml/min compared to the other four conditions. Differences in breathing between combinations of two conditions were compared by testing whether the differences within an individual were smaller than the differences between random pairs of individuals from the same 16 subjects. For almost all respiratory variables, and whatever the behavioural condition, there were highly significant similarities within an individual (p < 0.00025 on 32/80 comparisons). Under each condition, the differences within MZ twin-pairs were compared to the differences within random-pairs from the same subject population. There were highly significant similarities within twin-pairs for the airflow shape across all conditions. However, TI, TE and VT failed to consistently show significant similarities within twin pairs. Hence, an individual's airflow shape appears to be a fundamental characteristic which is conserved when behavioural condition and level of ventilation changes. Further, MZ twins have similar airflow shapes--whatever the behavioural situation. Hence, behavioural influences upon airflow shape act upon monozygous twin pairs in similar ways, or such influences were negligible under the conditions of the present study.

Adolescent↗

Ventilatory responses to exercise in humans lacking ventilatory chemosensitivity.

1. In healthy humans during aerobic exercise ventilation increases and mean arterial PCO2 usually remains constant over a wide range of CO2 production. 2. Congenital central hypoventilation syndrome (CCHS) is associated with ineffective chemoreceptor regulation of breathing and severe hypoventilation during sleep (requiring mechanical ventilation) reflecting abnormalities in the brainstem respiratory complex or its chemoreceptor input. Such patients can have adequate spontaneous ventilation during resting wakefulness and participate in normal activities. 3. If children with CCHS have normal ventilatory responses to exercise then chemoreceptors are not necessary for this ventilatory response or the resultant control of Pa,CO2 during exercise. We studied five children with CCHS (aged 8-17 years) with abnormally low ventilatory responses to steady-state increased end-tidal PCO2 (< 9 ml min-1 kg-1 mmHg-1) and five age-matched controls. 4. Depth and rate of breathing, end-tidal PCO2, end-tidal PO2, CO2 production, O2 utilization and heart rate were monitored during the following conditions: whilst subjects stood at rest; following the onset of treadmill exercise (4 m.p.h.); during steady-state exercise (4 m.p.h.); during an incremental maximal exercise test; and during recovery from exercise. 5. There were no significant differences in the ventilatory responses between CCHS subjects and controls during the onset of treadmill exercise, in the dynamic response in achieving the steady-state exercise, during steady-state exercise, in the recovery from steady-state exercise, or during incremental exercise (up to the point of presumed blood lactate accumulation, as indicated by gas exchange criteria). There was a very small mean increase in PCO2 in both groups during steady-state exercise (controls 1.4 mmHg; CCHS 2.2 mmHg). 6. The only differences which emerged between groups were (i) slightly more variability in PCO2 in the CCHS group during steady-state exercise, and (ii) the CCHS subjects did not hyperventilate, as the controls did, at exercise levels above the point of presumed blood lactate accumulation. 7. Breath-by-breath coefficient of variation of ventilation was significantly reduced in both groups during steady-state exercise compared to rest. There were no differences between groups in either state. 8. We conclude that chemoreceptors are not necessary for an appropriate ventilatory response to aerobic exercise. Hence, other stimuli, such as afferent information from the exercising limbs or signals related to activation of the motor cortex, can increase alveolar ventilation in close proportion to CO2 production. 9. The lack of hyperventilatory response to blood lactate accumulation during heavy exercise provides good evidence that these CCHS patients have ineffective peripheral chemoreception.

Adolescent↗

Changes in global cerebral blood flow in humans: effect on regional cerebral blood flow during a neural activation task.

1. The primary objective of this study was to examine in man, how induced changes in global cerebral blood flow (gCBF) affected a regional cerebral blood flow (rCBF) increase resulting from a neural activation task (opening of eyes). A secondary objective was to quantify how such induced changes in gCBF were distributed between representative regions of either predominantly grey matter or white matter. 2. Positron emission tomography with intravenous infusion of H2(15)O, was used to measure gCBF in six normal males. Concomitant measures of rCBF were obtained in three different regions of interest (ROI): a representative area of predominantly grey matter, a representative area of predominantly white matter and an area of visual cortex. 3. Cerebral blood flow was altered by establishing steady-state changes in PCO2 at a near constant ventilation of approximately 30 l min-1. The mean PET,CO2 (+/- S.D.) levels (mmHg) that resulted were: low, 21.8 +/- 1.8; normal, 39.8 +/- 1.0, and high, 54.8 +/- 1.2. The normal and high levels were obtained by adding appropriate amounts of CO2 to the inspirate. The corresponding mean gCBF levels across all six subjects with eyes closed were: low, 24.2 +/- 4.6; normal, 37.2 +/- 3.9 and high, 66.8 +/- 7.6 ml min-1 dl-1. 4. Blood flow in grey matter (insular cortex) and white matter (centrum semiovale) at normal levels of PCO2 averaged 56.8 +/- 10.1 and 20.3 +/- 3.4 ml min dl-1 respectively. As PCO2 rose, the increase in rCBF to grey matter was approximately three times greater than that to white matter. 5. An activation state of eyes open in a brightly lit room was compared to a baseline state of eyes closed in a darkened room at the three levels of PCO2 (and hence at three levels of gCBF). Over the whole gCBF range a significant (P = 0.028) effect of increasing rCBF in the visual cortex ROI was found in response to opening the eyes; the effect of this activation on rCBF was not significantly dependent (P = 0.34) on the PCO2 (and hence gCBF) level. The effect of the activation on the rCBF was apparently 'additive' to the rise of rCBF associated with PCO2-related gCBF increase. 6. The results confirm the need to normalize for changes in gCBF during studies of rCBF in response to an activation protocol. They also provide support for the use of an 'additive' model to achieve such normalization provided that other cortical areas behave in a similar manner to that of the visual cortex.

Adult↗

Personnalité ventilatoire--an overview.

An infinite number of possible combinations of tidal volume and breathing frequency, as well as pattern of airflow, can achieve the alveolar ventilation required for normal gas exchange. Individuals appear to select one particular pattern. This paper summarises our work relating to differences in the pattern of breathing between individuals when at rest and discusses the possible determinants of such individuality.

Adult↗

Reduced tidal volume increases 'air hunger' at fixed PCO2 in ventilated quadriplegics.

The act of breathing diminishes the discomfort associated with hypercapnia and breath-holding. To investigate the mechanisms involved in this effect, we studied the effect of tidal volume (VT) on CO2-evoked air hunger in 5 high-level quadriplegic subjects whose ventilatory capacity was negligible, and who lacked sensory information from the chest wall. Subjects were ventilated at constant frequency with a hyperoxic gas mixture, and end-tidal PCO2 was maintained at a constant but elevated level. VT was varied between the subjects' normal VT and a smaller VT. Subjects used a category scale to rate their respiratory discomfort or 'air hunger' at 30-40 sec intervals. In 4 of 5 subjects there was a strong inverse relationship between breath size and air hunger ratings. The quality of the sensation associated with reduced VT was nearly identical to that previously experienced with CO2 alone. We conclude that afferent information from the lungs and upper airways is sufficient to modify the sensation of air hunger.

Adult↗

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↗

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↗

The persistence of a respiratory 'personality' into stage IV sleep in man.

The characteristic pattern of breathing for an individual when awake at rest may be due to forebrain influences upon breathing. To examine this hypothesis we have studied the breathing pattern in 18 healthy subjects during relaxed wakefulness (W) and during Stage 4 sleep (S4), when forebrain influences upon breathing are absent or minimal. Inspiratory and expiratory times, respiratory frequency, tidal volume, and ventilation were quantified noninvasively by respiratory inductance plethysmography. The stability of respiratory variables between W and S4 sleep was tested within individuals. The results show that (i) individuals breathe differently from each other when awake and when in S4 sleep; the range between individuals during sleep being as large as it is when awake; (ii) differences in breathing pattern between two S4 periods within an individual are relatively small; (iii) the characteristic breathing pattern of an individual when awake tends to be maintained in S4 sleep. This persistence of a respiratory 'personality' into S4 sleep probably indicates that there are individual differences in respiratory rhythm generation in the absence of any forebrain influences upon breathing.

Adult↗

Individuality of breathing patterns in adults assessed over time.

Sixteen healthy adult subjects underwent two studies separated by 4-5 years to test whether their resting pattern of breathing was reproducible over time. From breath-by-breath analysis of airflow, measured with a pneumotachometer, the pattern of breathing was quantified in terms of individual respiratory variables; inspiratory time (TI), expiratory time (TE), total breath duration (TTOT), tidal volume (VT), VT/TI, TI/TTOT, and by taking TI, TE and VT all together (TRIAD). Also, the shape of the entire airflow profile was quantified by harmonic analysis (ASTER). A statistical analysis was designed to compare differences between the 1st and the 2nd recording within individuals with those differences observed between random pairs of recordings from the two studies in the same 16 individuals. It was found that all variables were significantly more similar within-individuals than between-individuals; this is best demonstrated when considering the ASTER and/or the TRIAD. It was concluded that the individuality of breathing pattern is maintained over a long period despite changes in smoking habit, weight, mild respiratory diseases, and other changes which occurred between the two studies in our subjects.

Adult↗

The breathing patterns of identical twins.

The resting breathing patterns of healthy adult identical twins were compared to see if there was any possible genetic component in the determination of this pattern. From breath-by-breath analysis of airflow, measured with a pneumotachometer (9 pairs of twins), the pattern of breathing was quantified in terms of individual respiratory variables; inspiratory time (TI), expiratory time (TE), total breath duration (TTOT), VT/TI, TI/TTOT, and by taking TI, TE and VT all together (TRIAD). Also, the airflow shape was quantified by harmonic analysis (ASTER). A second study was performed under more strictly defined conditions of rest and where the respiratory variables were estimated with respiratory inductance plethysmography to eliminate the possible effect of a facemask (5 pairs of twins). In each study, for each variable, the differences within twin-pairs were compared to the differences within random-pairs from the same subject population. In both studies, there were highly significant similarities within twin-pairs in the pattern of breathing, being best demonstrated when the entire 'shape' of the pneumotachogram (ASTER) or the spirogram (TRIAD) was considered.

Adolescent↗

Does the abnormal pattern of breathing in patients with interstitial lung disease persist in deep, non-rapid eye movement sleep?

Patients with interstitial lung disease (ILD) characteristically exhibit an increased ventilation and breathing frequency when awake. We wanted to see if these increases persisted during deep non-REM sleep. Using noninvasive techniques, we have quantified the pattern of breathing, arterial oxygen saturation, and transcutaneous PCO2 (PtcCO2) during standardized conditions of relaxed wakefulness and during Stage 4 (S4) sleep in eight patients with ILD and eight age-matched normal control subjects. The patients were given supplemental oxygen in order to prevent hypoxic ventilatory stimulation. The data were compared between the two groups during each of these states and also between states within each group. During wakefulness in the patients, respiratory frequency (f) and PtcCO2 were higher (p less than 0.001 and p less than 0.05, respectively) and inspiratory time (TI) and expiratory time (TE) were shorter (p less than 0.05 and p less than 0.001, respectively) than in the normal subjects. However, during S4 sleep, there were no significant differences between groups. Comparing wakefulness with S4 sleep: in the normal subjects during sleep, f and PtcCO2 were increased (p less than 0.01 and p less than 0.05, respectively), TE was shortened (p less than 0.01), and ventilation (VI) was unchanged. In contrast, in the patients, f decreased (p less than 0.001), TE lengthened (p less than 0.01), VI decreased (p less than 0.05), and the rise in PtcCO2 seen in the normal subjects during sleep did not occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Pharyngeal size and shape during wakefulness and sleep in patients with obstructive sleep apnoea.

Computed tomography has been used to study the pharyngeal airway during tidal breathing in wakefulness and during obstructive apnoeas in Non-REM sleep in patients with obstructive sleep apnoea. In supine subjects, contiguous transverse 10 mm sections were taken perpendicular to the posterior pharyngeal wall with a 2.1 s scan time. Studies during wakefulness showed that the narrowest section of the pharyngeal airspace was in the region posterior to the soft palate and that the minimal airway cross-sectional areas were significantly reduced in the group of patients with obstructive sleep apnoea compared to the group of control subjects without obstructive sleep apnoea. The studies during sleep showed that in all patients, the airspace posterior to the soft palate was a site of obstructive apnoeas. The length of the obstructed segment varied between patients, extending below the level of the soft palate in half the patient group. Airway narrowing and obstruction was due to posterior displacement of the soft palate and the tongue in the majority of patients, although lateral displacement of the pharyngeal walls was also observed. No occlusion was observed in the laryngopharynx although there was narrowing of oro- and laryngopharyngeal apertures below the site of obstruction during obstructive apnoeas. The size of the oropharyngeal airspace during wakefulness did not predict the presence of airway occlusion below the level of the soft palate when asleep. The variability between patients in the site(s) of upper airway obstruction during obstructive apnoeas have important implications for the choice of appropriate treatment in patients with obstructive sleep apnoea.

Adult↗

Sites and sizes of fat deposits around the pharynx in obese patients with obstructive sleep apnoea and weight matched controls.

It has been suggested that deposition of fat in the soft tissues surrounding the upper airway may be an important factor in the pathogenesis of obstructive sleep apnoea (OSA) in obese subjects. We have used magnetic resonance imaging to determine the site(s) and size(s) of fat deposits around the upper airway in six obese patients with OSA (116-153% of ideal body weight) and five weight-matched controls without OSA (107-152% of ideal body weight). In all subjects, large deposits of fat were present postero-lateral to the oropharyngeal airspace at the level of the soft palate. Significantly more fat was present in these regions in the patients with OSA (p = 0.03). Fat deposits in the soft palate were observed in 4 of the 6 patients with OSA but none of the controls. Fatty streaks were observed in the tongue in 2 of the 5 controls and 3 of the 6 patients with OSA. Fat deposits were observed anterior to the laryngopharyngeal airspace, in submental regions, in all obese subjects. This study shows that more fat is present in those areas surrounding the collapsable segment of the pharynx in patients with OSA, compared to equally obese control subjects without OSA.

Adipose Tissue↗

The effect of human heart-lung transplantation upon breathing at rest and during sleep.

We have assessed the contribution of intrathoracic pulmonary nerves to the control of breathing in humans. During relaxed wakefulness and during sleep the level, pattern and variability of breathing have been quantified in 8 healthy patients 1 month to 2 years after combined heart--lung transplantation. These data have been compared with similar data from both of 2 matched control groups; either healthy normal controls, or healthy patients after heart transplantation alone. We found no significant differences in the mean levels of respiratory variables between the 3 groups either during relaxed wakefulness or sleep. There were no significant differences between groups (other than would be expected by chance alone) either in the variability of breathing, or in the shapes of the frequency distributions of respiratory variables during these states. There were no respiratory disorders associated with sleep nor any disturbances in blood gases in any group. We conclude that in man breathing is remarkably normal, during relaxed wakefulness and during sleep, after chronic pulmonary denervation. When the ventilatory demands are minimal the human ventilation system functions normally in the absence of a control loop involving pulmonary proprioceptors and the medullary respiratory centres.

Adolescent↗

Evidence for individuality of breathing patterns in resting healthy man.

This study attempts to answer the question of whether there is a characteristic individuality of breathing pattern in conscious man. Measurements of breathing pattern, electroencephalograms and electrooculograms were made on 41 healthy individuals under standardised conditions of relaxed wakefulness, with a minimum of visual, auditory, and tactile input. Noninvasive measurement techniques were utilised and the subjects did not know that their breathing was being monitored. Measurement periods of only 5 min were used in order to avoid sleep. To estimate reproducibility, subjects were studied four times over two days. A variety of statistical tests on respiratory and cardiovascular variables indicate that the differences between individuals are highly significantly greater than the differences within an individual on repeated measurements under these standardised conditions. There was a high degree of reproducibility of breathing pattern within a subject; respiratory frequency was the most reproducible variable.

Adult↗

The effect of visual and auditory stimuli upon resting ventilation in man.

We have quantified the effect of visual, and auditory stimulation upon the breathing pattern in resting healthy man. Only noninvasive instrumentation was used. For the visual experiment we studied 36 subjects in each of three conditions: relaxed wakefulness with eyes closed (EC); with eyes open and directed at a white screen (EO); and whilst reading a standardised text (R). For the auditory experiment we studied 18 subjects under three analogous situations: no auditory input (N); listening to white noise (W); and listening to a story (V). In each study, all subjects underwent four replications (over two days) of one of the six permutations of the three experimental conditions; each condition lasted 5 min. A balanced analysis of variance on 10,368 breaths showed that, from baseline EC, both EO and R significantly increased respiratory frequency and ventilation by approximately 6%. Using 5184 breaths in the auditory study the analysis showed qualitatively similar results between analogous situations. The results demonstrate the importance of defining the conditions under which resting VI is measured.

Acoustic Stimulation↗

Respiratory and cardiovascular effects of central and peripheral intravenous injections of capsaicin in man: evidence for pulmonary chemosensitivity.

The respiratory and cardiovascular effects of capsaicin injection into the superior vena cava and an arm vein were studied in three normal subjects. No changes were seen in tidal volume, inspiratory time or expiratory time after capsaicin injection. Instantaneous heart rate, systolic blood pressure and diastolic blood pressure remained unchanged. Central and peripheral intravenous injections of capsaicin but not control solution above a threshold of 0.5 micrograms/kg produced dose-dependent sensations sequentially in the chest, face, rectum and extremities. The chest sensation, a 'raw, burning' feeling, occurred 3-4 s after central capsaicin injection. No subject reported feeling breathless. In one subject the maximum tolerable dose of capsaicin (4 micrograms/kg) produced paroxysmal coughing 3.9 s after a central injection. In two of the subjects capsaicin injection was repeated after inhalation of a 5% bupivacaine aerosol (aerodynamic mass median diameter 4.8 micron), sufficient to block the cough reflex to a 5% citric acid aerosol. Prior inhalation of local anaesthetic aerosol abolished the chest sensation after capsaicin injection; the other sensations were unaffected. This study demonstrates that stimulation of receptors accessible from the pulmonary vascular bed does not evoke the pulmonary chemoreflex in conscious man but can produce coughing. It provides evidence for the existence of a nociceptive system of nerve endings in the lung parenchyma that can be blocked by inhaled local anaesthetic aerosol.

Bupivacaine↗