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Biomedical subjects

S J England

Publications and source records attributed to S J England.

At least 19 recordsLinked to original sources

Respiratory muscle activation by chemical stimuli in awake and sleeping dogs.

The present findings in awake and sleeping dogs confirm the early observations in anesthetized cats (Bainton et al., 1978; Sears et al., 1982), and more recent studies in awake and sleeping humans (Takasaki et al., 1989), that suggest an asymmetry in pattern of respiratory motoneuron and muscle activation by central and peripheral chemoreceptor stimulation, with central chemoreceptor stimulation driving both inspiratory and expiratory mechanisms, and peripheral chemoreceptor stimulation driving inspiratory and inhibiting expiratory mechanisms. Because REM sleep inhibits the nondiaphragmatic muscles, which include the expiratory muscles, there is a reduction in CO2 response during this sleep stage. In contrast because the response to hypoxia is mediated predominantly by the diaphragm, which is not generally inhibited by REM sleep, there is less effect of REM sleep on the overall response to hypoxia. In addition to being of basic importance, these concepts may have important clinical implications.

Afferent Pathways

Expiratory muscle activity in anesthetized children: effect on the single breath technique.

Phasic expiratory activity of the abdominal muscles occurs in adults during halothane anesthesia, but has not been demonstrated in children. If present, abdominal muscle activity would preclude the use of recently developed tests of respiratory mechanics in children during anesthesia. We therefore measured abdominal muscle activity throughout induction of anesthesia with halothane in 10 patients between 1.5 and 9.5 years of age, seven with normal respiratory function and three with chronic airway obstruction. During induction of anesthesia with halothane in N2O and oxygen, the abdominal wall electromyograph (a-EMG) was continuously recorded from surface electrodes. At the same time, the expiratory time constant (tau a) was measured using the single breath test (SBT). The patients were then paralyzed with succinyl choline, and the a-EMG signal and expiratory time constant during paralysis (tau p) were recorded. The raw a-EMG signal and its moving time average were compared with the phase of respiration and with the end-tidal fraction of halothane (Fehalo), and the effect of abdominal muscle activity on tau a was noted. Of the 10 patients, 2 had no abdominal muscle activity at any time during induction. Of the remaining 8 patients, 3 had continuous abdominal muscle activity throughout induction, including one patient with asthma. In the remaining five patients, abdominal muscle activity was present during light halothane anesthesia and disappeared at increased Fehalo. When abdominal muscle activity was present, tau a was significantly less than tau p. It is concluded that abdominal muscle activity in expiration is undetectable during deep halothane anesthesia in most children.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Muscles

Cardiopulmonary effects of the volume recruitment manoeuvre in infant swine.

The volume recruitment manoeuvre is a non-invasive technique used to measure respiratory mechanics in infants. Because airway pressure increases during this manoeuvre, lung volume, compliance and cardiac output may change. In order to assess possible changes in cardiopulmonary function caused by the volume recruitment manoeuvre, we applied this technique to seven intubated infant swine breathing spontaneously during anaesthesia with halothane and N2O. Tidal volume (VT), respiratory frequency, arterial blood gases, cardiac output (CO) and total respiratory compliance were measured before and after the manoeuvre. In three swine functional residual capacity (FRC) was measured by helium dilution before the manoeuvre, and in four swine diaphragmatic EMG was recorded continuously. Finally, all swine were paralysed during volume recruitment to assess the contribution of the respiratory muscles to post-manoeuvre respiratory mechanics. VT and f increased immediately after the manoeuvre but there were no significant changes in PaCO2, or alveolar to arterial oxygen gradient. There was a small but statistically significant decrease in CO. Compliance increased by 17.8 +/- 3.6 per cent and FRC increased by a mean of 41.1 ml (or 51.9 per cent increase above the baseline FRC). The increase in FRC could not be explained by active mechanisms since the diaphragmatic EMG showed no post-inspiratory activity and neuromuscular paralysis did not decrease FRC. We conclude that the volume recruitment manoeuvre increases FRC and compliance by recruiting collapsed alveoli, and this effect must be taken into consideration when applying this test to infants.

Anesthesia, Inhalation

Expiratory airflow patterns and gas exchange in the newborn infant: results of model simulations.

A mathematical model simulating the newborn human infant's respiratory system was used to study the effects on gas exchange of varying expiratory airflow pattern and end expiratory lung volume (FRC). Inspiratory flow was modelled as a square wave and was constant for all simulations as were inspiratory and expiratory times. Expiratory airflow was also modelled as a square wave and was varied between 21 and 75 ml/sec with FRC held constant at either 30.2 or 21.2 ml/kg for each simulation. At a given FRC, expiratory airflow pattern had only a trivial effect on blood gases in the steady state. Comparing the extreme cases, fast expiration (75 ml/sec) at low FRC (21.1 ml/kg) with slow expiration (21 ml/sec) at high FRC (30.2 ml/kg), arterial PO2 was 3.8 mm Hg higher and arterial PCO2 1.0 mm Hg lower under the latter conditions. However, when short apneas were imposed, blood gases deteriorated less precipitously following the slow expiration at high FRC. We conclude that expiratory airflow retardation and the resultant elevation in end expiratory lung volume do not greatly enhance gas exchange in the healthy full term infant. However, mechanisms which slow expiratory airflow do provide a buffer for gas exchange during the short apneas often observed in infants.

Apnea

Glottic dimensions in healthy men and women.

Glottic aperture is important in modulating respiratory system resistance. Male patients with obstructive sleep apnea (OSA) have a smaller glottic cross-sectional area compared to controls. Since OSA has a strong male predominance, we reasoned that glottic dimensions may differ between healthy men and women. Therefore, we utilized the acoustic reflection to measure glottic cross-sectional area in 44 non-smoking, non-obese, healthy subjects, 25 men and 19 women. Glottic area was measured during a continuous slow expiration from total lung capacity (TLC) to residual volume (RV). We compared glottic areas in men and women at three lung volumes: TLC, 50% of vital capacity (VC), and RV. We found that in all but 2 subjects, glottic areas at TLC was greater than at 50% VC or RV. At any given lung volume, there was no significant difference in glottic area between men and women. The reduction in glottic area between TLC and RV was also similar between men and women (36 +/- 24% and 33 +/- 21%, respectively). However, this reduction in glottic area occurred mainly at low lung volumes in women, and more uniformly throughout the vital capacity range in men. We conclude that changes in glottic dimensions are dependent on lung volume, that healthy men and women have similar glottic areas, and that the glottic aperture shows similar variation with lung volume among both sexes.

Adult

A model of the maturation of respiratory control in the newborn infant.

A model of automatic neonatal respiratory control has been constructed as an aid in the investigation of a possible maturation in respiratory control loops during the newborn period. The primary objective was to provide a framework for investigating this hypothesis without the need for external stimuli or invasive measurements. Spontaneous sighs provide a physiological disturbance to the respiratory system by transiently altering the levels of the blood gases. The dynamic ventilatory response following such a disturbance was modeled. A change from a highly damped to less damped pattern was found when model parameter values were varied to mimic maturation in the neonatal period. A perturbation model analysis demonstrated the dynamic ventilatory response is most sensitive to factors affecting the gain of the peripheral chemoreflex loop. It is concluded that the model provides valuable insight into the hypothesis that the peripheral chemoreflex matures during the neonatal period and provides a viable method for testing this in the human infant.

Humans

Influence of phasic afferent information on phrenic neural output during hypercapnia.

We measured the moving time average (MTA) of the phrenic neurogram before and after removal of phasic afferent information from the lungs, chest wall, and oscillations in blood gases by using constant-flow ventilation (CFV). Anesthetized dogs were studied at various levels of steady-state and progressive hypercapnia during spontaneous breathing and during CFV. When steady-state and progressive hypercapnia were compared, the frequency and height of the MTA phrenic neurogram were independent of the rate of induction of hypercapnia during each mode of ventilation. During spontaneous ventilation, the response to hypercapnia comprised mainly an increase in frequency with only a slight increase in the amplitude of the MTA phrenic waveform. During muscular paralysis and CFV, the responses were similar to those observed after vagotomy with mainly an increase in the amplitude and only a small increase in frequency. For both spontaneous breathing and CFV, increases in frequency were achieved mainly by a shortening in expiratory time with the inspiratory time remaining relatively constant. Our data support the concept of a centrally patterned respiratory generator, whose inherent pattern is modified by phasic feedback from peripheral receptors mainly of vagal origin.

Afferent Pathways

Importance of vagal afferents in determining ventilation in newborn rats.

We studied the effect of acute bilateral vagotomy on ventilation and ventilatory pattern in rats. In 1- to 6-day-old unanesthetized rats, vagotomy resulted in a substantial decrease (38%) in ventilation during air breathing. After vagotomy there was a threefold increase in tidal volume (VT), inspiratory time (TI) doubled, and expiratory time (TE) was six times longer. When studied under isoflurane anesthesia, newborn rats showed decreases in ventilation similar to that observed without anesthesia, whereas anesthetized adult rats had no consistent changes in ventilation. Adult and newborn rats had nearly identical proportionate increases in VT and TI after vagotomy, but TE lengthened to a greater extent in the newborns. Additionally, we demonstrated a significant decrease in ventilation when 100% O2 rather than air was supplied to nonvagotomized unanesthetized newborn rats. Ventilation decreased by 19% after vagotomy under hyperoxic conditions. We conclude that vagal afferent input, probably of pulmonary mechanoreceptor origin, provides positive feedback to respiration in newborn rats and that newborn rats greater than 24 h old also have a degree of peripheral chemoreceptor drive during air breathing.

Afferent Pathways

Comparison of diaphragmatic fatigue in newborn and older rabbits.

The ability to maintain occlusion pressure (i.e., fatigability) during activation of the diaphragm via phrenic nerve stimulation was compared in newborn (less than 14 days old) and older (greater than 30 days old) rabbits. The younger animals had lower maximum inspiratory pressures (MIP) and markedly greater falls in pressure during sustained diaphragmatic contractions at greater than 40% MIP than did the older animals. Histological analysis showed a paucity of high-oxidative type I fibers in the diaphragms of the young animals. We therefore conclude that the newborn rabbit diaphragm is extremely susceptible to fatigue and that this susceptibility correlates with the distribution of muscle fiber types.

Age Factors

Tracheomalacia: an experimental animal model for a new surgical approach.

Tracheomalacia was created by removing the posterior 50% of the circumference of eight cartilage rings (5-6 cm in length) from the intrathoracic trachea in each of 12 piglets while leaving the mucosa intact. In 6 animals an autologous, free tibial periosteal graft was applied over the defect (graft group). The remaining 6 piglets served as the control group. In all animals, a silastic stent was left in the trachea for 2 weeks to prevent immediate tracheal collapse. The presence of tracheomalacia was assessed 6-8 weeks after surgery. At bronchoscopy total tracheal collapse during coughing occurred only in the controls. As the animals went from quiet breathing to coughing, mean intrathoracic pressure increased from 5 to 80 cm H2O in both groups, and average sagittal tracheal diameter decreased by 10% in the graft group and 71% in the controls. During coughing, mean resistance to airflow across the defect increased by 0.005 +/- 0.002 cm H2O/liter/min in the graft group, by 0.083 +/- 0.96 cm H2O/liter/min in the controls (P less than 0.005), and by 0.027 cm H2O/liter/min at the same tracheal level in two normal pigs. At sacrifice 12 weeks postoperatively, bone and collagenized fibrous tissue had been produced by all grafts, without evidence of stricture. This study shows that experimentally induced tracheomalacia can be treated successfully by the application of an autologous periosteal tibial graft, which becomes incorporated into the weakened tracheal wall.

Airway Resistance

Role of upper airway in ventilatory control in awake and sleeping dogs.

We examined the role of the upper airway in the regulation of the pattern of breathing in six adult dogs during wakefulness and sleep. The dogs breathed through a fenestrated endotracheal tube inserted through a tracheostomy. The tube was modified to allow airflow to be directed either through the nose or through the tracheostomy. When airflow was diverted from nose to tracheostomy there was an abrupt increase in the rate of expiratory airflow, resulting in prolongation of the end-expiratory pause but no change in overall expiratory duration or respiratory frequency. Furthermore, electromyogram recordings from implanted diaphragmatic and laryngeal muscle electrodes did not show any changes that could be interpreted as an attempt to delay expiratory airflow or increase end-expiratory lung volume. The effects of switching from nose to tracheostomy breathing could be reversed by adding a resistance to the endotracheal tube so as to approximate upper airway resistance. The findings indicate that under normal conditions in the adult dog upper airway receptors play little role in regulation of respiratory pattern and that the upper airway exerts little influence on the maintenance of end-expiratory lung volume.

Animals

Diaphragmatic work of breathing in premature human infants.

Present methods of assessing the work of breathing in human infants do not account for the added load when intercostal muscle activity is lost and rib cage distortion occurs. We have developed a technique for assessing diaphragmatic work in this circumstance utilizing measurements of transdiaphragmatic pressure and abdominal volume displacement. Eleven preterm infants without evidence of lung disease were studied. During periods of minimal rib cage distortion, inspiratory diaphragmatic work averaged 5.9 g X cm X ml-1, increasing to an average of 12.4 g X cm X ml-1 with periods of paradoxical rib cage motion (P less than 0.01). Inspiratory work was strongly correlated with the electrical activity of the diaphragm as measured from its moving time average (P less than 0.05). Assuming a mechanical efficiency of 4% in these infants, the caloric cost of diaphragmatic work may reach 10% of their basal metabolic rate in periods with rib cage distortion. When lung disease is superimposed, the increased metabolic demands of the diaphragm may predispose preterm infants to fatigue and may contribute to a failure to grow.

Diaphragm

Comparison of calibration methods for respiratory inductive plethysmography in infants.

In infants under the age of 6 mo respiratory inductive plethysmograph (RIP)-calculated tidal volumes (VT) were compared with simultaneously measured volumes using a pneumotachograph (PNT) to 1) assess whether using multiple points (MP) along the inspiratory profile of a breath is superior to using only VT when calculating volume-motion (VM) coefficients, 2) verify the assumption of independent contributions of the abdomen and rib cage to VT, which was accomplished by extending the normal RIP model to include a term representing interaction between these two compartments, and 3) investigate whether VM coefficients are sleep-state dependent. Neither use of multiple points nor inclusion of the interacting term improved the performance of the RIP over that observed using a simple two-compartment model with VT measurements. However, VM coefficients obtained during quiet sleep (QS) were not reliable when used during rapid-eye-movement (REM) sleep, suggesting that coefficients obtained during one sleep state may not be applicable to another state where there is a substantial change in the relative abdominal/rib cage contributions to VT.

Humans

Evaluation of respiratory inductive plethysmography in infants weighing less than 1,500 grams.

Calibration of the respiratory inductive plethysmograph (RIP) was performed in premature infants weighing less than 1,500 g. In only 25% of the studies was an acceptable calibration achieved, as assessed by statistical comparison of simultaneously measured pneumotachygraph and RIP tidal volumes. In 6 infants, dead space loading or air injection was performed in an attempt to alter abdominal and rib cage volume contributions and thereby improve the calibration. Neither of these maneuvers resulted in an improvement of the accuracy of the RIP calibration coefficient. We conclude that, when calibrated by the least squares technique, the reliability of inductive plethysmography in measuring tidal volume in small infants is low. This is presumably because they have very small tidal volumes and highly compliant rib cages.

Female

Comparison of methods of measurement of compliance of the respiratory system in children.

Compliance of the respiratory system (Crs) was compared using 2 previously described methods, namely, the passive expiratory flow and multiple occlusion techniques. These 2 methods have the advantage of being totally noninvasive, but both have limitations precluding their use in some circumstances. The results of this study of 10 intubated patients, who varied widely in age (premature newborn to adolescence) and diseases, showed no significant difference between the Crs obtained by the 2 methods. The Crs measurements can therefore be used interchangeably, the choice of technique being dependent on the subjects' clinical state.

Child

Influence of the upper airway on breathing pattern and expiratory time constant in unanesthetized dog pups.

Unanesthetized dog pups (2 to 31 days old) respond to sudden opening of a tracheal cannula to atmospheric pressure with a marked increase in breathing frequency. This response is achieved with a 25% decrease in inspiratory and 40% decrease in expiratory times. Expiratory thyroarytenoid muscle activity increased concomitantly, while inspiratory diaphragmatic and posterior cricoarytenoid muscle activities were reduced. These responses are interpreted as a compensatory mechanism for maintenance of an elevated end-expiratory lung volume with functional loss of the upper airway. The changes in expiratory time and thyroarytenoid muscle activity were not observed when positive pressure was applied at the trachea. The expiratory time constant was assessed during spontaneous breathing. The mean value was twice as long during nasal breathing than during tracheal breathing. The nasal value was substantially increased when the thyroarytenoid muscle was active during expiration.

Animals

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.

Airway Resistance