Sandra J. England

Total resistance of the respiratory system in preterm infants with and without an endotracheal tube

The passive compliance and resistance of the respiratory system were measured in 12 spontaneously breathing newborn infants before and after endotracheal extubation. End-inspiratory airway occlusions were used to relax the respiratory muscles, allowing occlusion pressure to be measured and respiratory system compliance and resistance to be calculated from the flow volume relationship of the subsequent passive expiration. Airway pressure was measured from an endotracheal tube or a face mask, expiratory flow from a pneumotachograph, and expiratory volume from the integrated flow signal. In six of the infants, diaphragmatic electromyography was also performed before and after extubation. Resistance and EMG findings were both decreased by extubation (mean decrease 43.9%, P less than 0.001 and 27.3%, P less than 0.05, respectively), but compliance was unchanged. Thus, by substantially increasing resistance, an endotracheal tube causes the diaphragm to increase its activity to maintain ventilation.

Laryngeal muscle and diaphragmatic activities n conscious dog pups

A new chronic animal preparation (i.e. puppies) for the study of respiratory laryngeal muscle activity is described. Posterior cricoarytenoid (PCA), thyroarytenoid (TA) and diaphragmatic activities were monitored in conscious puppies (13-43 days old) using chronically implanted electrodes. PCA activity was prominent during inspiration in all behavioral states. TA and post-inspiratory diaphragmatic activities were consistently high during expiration in quiet wakefulness and quiet sleep, but expiratory TA activity decreased dramatically and post-inspiratory diaphragmatic activity became highly variable in rapid eye movement sleep. There was also a tendency for these expiratory muscle activities to become less pronounced with increasing postnatal age. When a chronically implanted, low resistance T-tube tracheal cannula was suddenly opened, thus effectively eliminating the effects of upper airway resistance on airflow, respiratory frequency dramatically increased. These results indicate that the puppy exhibits muscle activities consistent with the maintenance of an elevated end-expiratory lung volume achieved by the retardation of expiratory airflow using the larynx and diaphragm.

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.

Hypoxia associated with helium-oxygen therapy in neonates

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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.

Laryngeal muscle activities during progressive hypercapnia and hypoxia in awake and sleeping dogs

Laryngeal, intercostal and diaphragmatic muscle activities were recorded during progressive hypercapnia and hypoxia in dogs with chronically implanted electrodes. As ventilation increased during progressive chemoreceptor stimulation, inspiratory activity of the posterior cricoarytenoid muscle, a laryngeal abductor, and of the cricothyroid muscle were augmented. When expiratory flow rates reached 2-3 times resting levels, both of these muscles were also active during expiration and recruitment of the internal intercostal muscles was observed. The thyroarytenoid muscle, a laryngeal adductor, was active only rarely and no consistent activation of this muscle was observed with either hypercapnia or hypoxia. The patterns of muscle activation in response to respiratory stimulation were not different during wakefulness, slow wave sleep, and rapid eye movement sleep. The results indicate that the laryngeal muscles are activated during hypercapnia and hypoxia in a manner which reduces both inspiratory and expiratory airflow resistance regardless of sleep-wakefulness state.

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.

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

A mathematical model simulating the newborn human infants 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.

Antenatal Exposure to Hypoxia Results in Increased Endothelial Nitric Oxide Synthase (eNOS) in the Rat Carotid Body (CB) |[diams]| 253

Rat carotid bodies contain eNOS which is postulated to contribute to CB inhibition in response to hypoxia. We hypothesised that chronic antenatal hypoxia would cause an elevation of this inhibitory enzyme. Three rat dams were exposed to 21% O2 (control) and three to 12% O2 (chronic hypoxia) beginning in the midsecond trimester (10 days prior to delivery). No dam delivered prematurely. There were no abortuses or stillbirths and no pups had congenital malformations. The exposures were continued postnatally. On postnatal days 2 and 6, pups (n=31) were weighed sacrificed, and the carotid bodies excised. CB tissue levels of eNOS were analyzed by quantitative immunofluorescent histochemistry. Body weights were lower and growth was attenuated in the hypoxic animals (p<0.05). On day 2, eNOS levels in the hypoxic animals were significantly higher than in controls by an average of 126% (p=0.007). While eNOS levels declined in the hypoxic animals by day 6, they remained elevated above control by an average of 34% (p=.005). We conclude that antenatal hypoxia results in enhanced inhibition of the carotid chemoreceptors through upregulation of eNOS. This enzyme may act both intra- and extravascularly on the chemoreceptor mechanism to limit the carotid afferent activity in response to hypoxia.

HYPOXIA-INDUCED CHANGES IN THE MATURATION OF NITRIC OXIDE SYNTHASE (NOS) IN THE CAROTID BODY (CB). 236

HYPOXIA-INDUCED CHANGES IN THE MATURATION OF NITRIC OXIDE SYNTHASE (NOS) IN THE CAROTID BODY (CB). 236