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Biomedical subjects

O P Mathew

Publications and source records attributed to O P Mathew.

At least 55 records · Page 3Linked to original sources

Acute effect of cigarette smoke on laryngeal receptors.

Upper airway exposure to cigarette smoke elicits reflex changes in breathing pattern. To examine whether laryngeal afferents are affected by cigarette smoke, neural activity was recorded from the peripheral cut end of superior laryngeal nerve in anesthetized dogs. A box-balloon system, connected to the breathing circuit, allowed smoke to be inhaled spontaneously through the isolated upper airway while preserving its normal respiratory flow and pressure. Our results showed the following. Inhalation of cigarette smoke (25-50% concentration, 300-400 ml) caused a marked increase in activity of laryngeal irritant receptors which were either silent or randomly discharging during control breathing [their activity increased from a control value of 1.67 +/- 0.50 (mean +/- SE; n = 21) to a peak of 5.03 +/- 0.85 impulses/s in 11-15 s]. The activity of laryngeal cold receptors was reduced to 77.3 and 63.8% of control (n = 9) during the two breaths of smoke inhalation, respectively. After returning toward the base-line activity, a more pronounced inhibition (26.3% of control) occurred at three to nine breaths after the smoke inhalation. A small but significant decrease (88.5% of control) in the inspiratory discharge of laryngeal mechanoreceptors was observed during the first test breath. These effects were independent of the CO2 content of the smoke. Furthermore, there was no difference between the responses of these laryngeal afferents to high- and low-nicotine cigarette smoke.

Animals↗

Effect of cold air on laryngeal mechanoreceptors in the dog.

We have previously described laryngeal receptors specifically activated by cooling. The aim of this study is to determine the effect of cold air on laryngeal mechanoreceptors responding primarily to transmural pressure and respiratory movements of the larynx. We have recorded action potentials from 30 single fibers in the peripheral cut end of the internal branch of the superior laryngeal nerve of 11 anesthetized, spontaneously breathing dogs. Of 29 receptors studied with a constant flow of cold air through the isolated upper airway 13 showed a marked reduction in their discharge (0 to 15% of control), 10 showed a moderate decrease (16 to 84% of control) and the remaining 6 were minimally affected. Seven of the 29 receptors showed, prior to the inhibition, a transient initial stimulation. Transient state responses of the most affected receptors lagged behind laryngeal temperature. Three of the most affected endings were also studied during spontaneous breathing of cold air; to a progressive decrease in laryngeal temperature corresponded a progressive decrease in receptor activity. Susceptibility of the receptors to laryngeal cooling and topical anesthesia did not closely correlate. Our results indicate that in evaluating the reflex responses to upper airway cooling both excitation of cold receptors and inhibition of laryngeal mechanoreceptors should be taken into account.

Action Potentials↗

Effects of airway cooling on tracheal stretch receptors.

We studied the effect of cold air on tracheal slowly adapting stretch receptors (SAR) in 6 anesthetized, spontaneously breathing dogs. Air at constant flow and two different temperatures was passed through an isolated segment of the extrathoracic trachea. We recorded SAR action potentials, esophageal pressure, tracheal pressure and temperature. With a reduction in tracheal temperature of approximately 10 degrees C the steady state response of 30 SARs to a distending pressure of 1.0 kPa decreased to 75% of control (P less than 0.001). At lower distending pressure the inhibitory effect of tracheal cooling decreased: 87% of control at 0.5 kPa (P less than 0.05, n = 8) and 96% of control at 0.2 kPa (P greater than 0.05, n = 8). The response of 13 tracheal SARs to sinusoidal pressure oscillations (0.15 kPa) superimposed on a bias pressure (0.5 kPa) was reduced (P less than 0.01) by local cooling to the same extent at the 2 pressure extremes ('peak' value = 71% of control; 'valley' = 67% of control), resulting in a similar change in receptor discharge within the oscillatory cycle. The inhibitory effect of airway cooling on stretch receptors may play a role in cold-induced bronchoconstriction.

Action Potentials↗

Effects of cooling on laryngeal reflexes in the dog.

We investigated the reflex effects of laryngeal cooling on posterior cricoarytenoid (PCA) muscle activity, breathing pattern, arterial blood pressure and heart rate. We performed experiments on 9 anesthetized, spontaneously breathing dogs. Laryngeal temperature was decreased by passing cold air through the functionally isolated larynx while the dog was breathing through a tracheostomy. Inspiratory and expiratory durations, esophageal pressure, peak PCA activity, heart rate and blood pressure did not change significantly during laryngeal cooling. Upon interruption of cold airflow, while the laryngeal temperature was returning to control values, we assessed PCA response to upper airway occlusion. At laryngeal temperatures of 20-25 degrees C the peak PCA activity during upper airway occlusion was approximately 2/3 of that observed at control temperature (approximately equal to 33 degrees C). This difference was abolished by topically applied anesthetics or by superior laryngeal nerve section. In addition, we recorded from 4 laryngeal mechanoreceptors stimulated by negative pressure; their response to upper airway occlusion was reduced to 1/2 by laryngeal cooling. These results indicate that laryngeal cooling has a marked depressive effect on the PCA response to collapsing pressure in the larynx, thereby compromising the mechanism subserving upper airway patency.

Animals↗

Effect of upper airway pressure pulses on breathing pattern.

Importance of the time of application of upper airway pressure pulses on breathing pattern was investigated in 19 anesthetized, spontaneously breathing rabbits. The upper airway was functionally isolated into a closed system. A servo-respirator, triggered by the inspiratory activity of the diaphragm, was used to apply pressure pulses to the isolated upper airway. Negative pressure pulses of -5, -10, and -15 cm H2O when applied in early inspiration (within the first half) produced a reversible inhibition of inspiration in most trails (86.2%). This resulted in a prolongation of inspiratory duration (TI) and a decrease in mean inspiratory drive (P.Dia/TI) whereas peak diaphragm (P.Dia) activity and expiratory duration (TE) remained largely unaffected. In the remaining 13.8% of trials, an irreversible inhibition with short TI and reduced P.Dia activity was observed. In contrast, with late application of negative pressure pulses the only significant change was a shortening of TI. When positive pressure pulses were applied during expiration, no significant change in TE occurred with either early or late application. A significant prolongation of subsequent TI was seen irrespective of the time of positive pressure application. These results indicate that time of application during the respiratory cycle is an important variable in determining the response to upper airway pressure pulses.

Animals↗

Control of respiratory activity of the genioglossus muscle in micrognathic infants.

The genioglossus (GG) muscle activity of four infants with micrognathia and obstructive sleep apnea was recorded to assess the role of this tongue muscle in upper airway maintenance. Respiratory air flow, esophageal pressure, and intramuscular GG electromyograms (EMG) were recorded during wakefulness and sleep. Both tonic and phasic inspiratory GG-EMG activity was recorded in each of the infants. On occasion, no phasic GG activity could be recorded; these silent periods were unassociated with respiratory embarrassment. GG activity increased during sigh breaths. GG activity also increased when the infants spontaneously changed from oral to nasal breathing and, in two infants, with neck flexion associated with complete upper airway obstruction, suggesting that GG-EMG activity is influenced by sudden changes in upper airway resistance. During sleep, the GG-EMG activity significantly increased with 5% CO2 breathing (P less than or equal to 0.001). With nasal airway occlusion during sleep, the GG-EMG activity increased with the first occluded breath and progressively increased during the subsequent occluded breaths, indicating mechanoreceptor and suggesting chemoreceptor modulation. During nasal occlusion trials, there was a progressive increase in phasic inspiratory activity of the GG-EMG that was greater than that of the diaphragm activity (as reflected by esophageal pressure excursions). When pharyngeal airway closure occurred during a nasal occlusion trial, the negative pressure at which the pharyngeal airway closed (upper airway closing pressure) correlated with the GG-EMG activity at the time of closure, suggesting that the GG muscle contributes to maintaining pharyngeal airway patency in the micrognathic infant.

Cleft Palate↗

Laryngeal receptors and their reflex responses.

The afferent activity originating from the larynx shows a considerable respiratory modulation. Receptors responding to pressure changes, inspiratory airflow (cold), and laryngeal movements have been identified. In addition, other receptors without a respiratory modulation are also described. Possible reflex effects of these receptors on breathing pattern, upper airway patency, and defense mechanisms in both adults and newborns are discussed.

Bronchial Spasm↗

Laryngeal cold receptors.

We have previously demonstrated the presence of specific laryngeal 'flow' receptors activated independently of transmural pressure. This study considers the operational characteristics of these endings. In 15 anesthetized dogs we recorded single unit action potentials from the peripheral cut end of the internal branch of the superior laryngeal nerve. All the 30 laryngeal 'flow' receptors studied showed an inspiratory modulation when the dog was breathing room air at 26 degrees C and 55% relative humidity (laryngeal temperature approximately equal to 34 degrees C) through the upper airway. All the receptors became silent when the temperature of the inspired air was raised to 36-40 degrees C, 100% relative humidity (laryngeal temperature between 35 and 38 degrees C) and increased their activity when the temperature in the larynx was decreased either by lowering the temperature or the humidity of the inspired air. Fourteen laryngeal 'flow' receptors were tested with a steady flow of air, directed through the isolated in vivo larynx, at different temperatures and saturated with water vapor. Their discharge rate was found to be inversely related to laryngeal temperature (from 35 to 25 degrees C) and independent of airflow. Their rate of adaptation indicates a high dynamic sensitivity. In the isolated larynx preparation these receptors were activated by airflow in both inspiratory and expiratory directions provided that laryngeal temperature was lower than 35 degrees C. We conclude that the previously described laryngeal 'flow' receptors operate as thermoreceptors activated by cooling.

Animals↗

Role of intrinsic muscles and tracheal motion in modulating laryngeal receptors.

Recording from the superior laryngeal nerve discloses a respiratory modulated activity even in the absence of airflow and pressure changes in the larynx. The present study evaluates the relative contribution of intrinsic laryngeal muscle activity and transmitted tracheal movement on the respiratory modulation of laryngeal mechanoreceptors. Seventy-four receptors were studied in 22 anesthetized spontaneously breathing dogs. The modulation of 31 receptors depended solely on laryngeal muscle activity since it was abolished by cold block of laryngeal nerves. Twelve receptors were primarily activated by tracheal movement since tracheal stabilization alone reduced or abolished their modulation. The respiratory modulation of the remaining 31 receptors was found to be dependent on both laryngeal muscle activity and tracheal movements. Lidocaine (2%) was applied to the receptor field of 13 endings; the results indicate that while some receptors are located superficially (blocked within 1 min) others are located in deeper structures (not affected in 30 min). These receptors may be involved in the precise coordination of laryngeal muscle activity and could play a role in the regulation of breathing pattern and airway patency due to their pressure sensitivity.

Animals↗

Observations made on severe apneic spells in two infants at risk for sudden death.

We have studied the sequence of events during prolonged apneic spells in two infants who, by virtue of multiple risk factors or ultimate death, were at risk for sudden death. Using techniques to quantitate airflow and pharyngeal airway pressures, we have reported many descriptive aspects of the apnea in these infants. Specifically, we have noted that severe apneic spells in these infants were accompanied by a wide spectrum of lengths and types of shorter apneas. In the case of infant A, the most severe spells occurred in clusters. Physiologic phenomena usually considered normal (sighs, swallows, etc.) often occurred in association with the apneic spells. In addition, we found that: 1) mixed apnea was the clinically significant form of apnea; 2) in mixed apnea, the site of obstruction was in the pharynx; 3) obstruction often occurred at the beginning of the spells; and 4) this obstruction occurred progressively over a series of breaths prior to the spell and resolved in a similar fashion. Theophylline, in one infant, decreased the incidence of apnea.

Airway Resistance↗

Breathing pattern and ventilation during oral feeding in term newborn infants.

The effect of oral feeding on breathing pattern and ventilation was studied in 19 healthy term neonates in the semiupright supine position. Ventilation was measured with a nasal flowmeter, and sucking pressure via a modified nipple that permitted milk delivery. The feeding pattern in these infants consisted of an initial period of continuous sucking followed by intermittent sucking for the remainder of the feed. A significant reduction in minute ventilation (P less than 0.01) was observed during continuous sucking, and resulted entirely from a reduction in breathing frequency (P less than 0.01). Tidal volume did not change (P greater than 0.05), but prolongation of expiration (P less than 0.01) and shortening of inspiration (P less than 0.05) were also observed. During intermittent sucking, the minute ventilation was similar to that of the control period. However, smaller but significant changes in breathing frequency and in duration of inspiration and expiration persisted during intermittent sucking. Our results document a significant reduction in ventilation during the initial part of oral feeding in term neonates, and subsequent recovery with continued feeding. Depending on the magnitude of this reduction in ventilation, cyanosis and bradycardia may develop in some infants during oral feeding.

Bottle Feeding↗

Resolution of pneumothorax in neonates.

The resolution time of pneumothorax in neonates requiring tube thoracotomy is not known. We found that 28%, 50%, and 83% of 54 pneumothoraces in 40 neonates resolved within 24, 96, and 168 h of tube thoracotomy, respectively. Pneumothoraces that persisted beyond 168 h were in infants requiring ventilatory assistance. Moreover, a significantly (p less than .05) greater number of preterm infants with persistent pneumothorax developed chronic lung disease compared to preterm infants in whom pneumothorax resolved by 168 h.

Birth Weight↗

Reflex effects and receptor responses to upper airway pressure and flow stimuli in developing puppies.

We studied the changes in breathing pattern due to pressure and airflow stimuli applied to isolated upper airway in nine 1- to 14-day-old and six 29- to 35-day-old anesthetized puppies breathing through a tracheostomy. Negative-pressure and flow, both inspiratory and expiratory, altered the breathing pattern only in the 1- to 14-day-old puppies, whereas positive pressure was ineffective in both age groups. Negative pressure caused apnea in 12% of the trials, expiratory flow in 18%, and inspiratory flow in 21%. When apnea did not occur there was a significant prolongation of inspiratory and expiratory time and a decrease of tidal volume of the first breath following the application of negative pressures. Section of the superior laryngeal nerves abolished the responses to pressure and flow. In nine 1- to 14-day-old and four 29- to 35-day-old puppies we recorded the activity of single units of the superior laryngeal nerves. We identified specialized receptors responding to pressure (68.5%), flow (2.7%), and contraction of upper airway muscles (drive, 28.8%). All types of receptors had a prevalent inspiratory-related activity. In the younger age group the discharge rate of pressure receptors at comparable negative pressures was lower than in older puppies. The strong inhibitory influences originating from the upper airway in the early stages of development presumably reflect different integrative properties of the central nervous system.

Animals↗

Assessment of pharyngeal airway stability in normal and micrognathic infants.

A current hypothesis for obstructive sleep apnea states that 1) negative airway pressure during inspiration can collapse the pharyngeal airway, and 2) neural control of pharyngeal airway-dilating muscles is important in preventing this collapse. To test this hypothesis we performed nasal mask occlusions to increase negative pharyngeal airway pressures during inspiration in eight normal and five micrognathic infants. Both groups developed midinspiratory pharyngeal obstruction, but obstruction was more frequent in micrognathic infants and varied in some infants with sleep state. The airway usually reopened with the subsequent expiration. The occasional failure to reopen was presumably due to pharyngeal wall adhesion. If airway obstruction occurred in sequential breaths during multiple-breath nasal mask occlusions in normal infants, there was a breath-by-breath change in the airway pressure associated with airway closure (airway closing pressure); the airway closing pressure became progressively more negative. Micrognathic infants showed less ability to improve the airway closing pressure, but this ability increased with age. These findings suggest that nasal mask occlusion can test the competence of the neuromuscular mechanisms that maintain pharyngeal airway patency in infants. Micrognathic infants had spontaneous midinspiratory pharyngeal airway obstructions during snoring. Their episodes of obstructive apnea began with midinspiratory pharyngeal obstruction similar to that seen during snoring and nasal mask occlusions. These findings imply a similar pathophysiology for snoring, spontaneous airway obstruction, and obstruction during snoring.

Airway Obstruction↗

Laryngeal influences on breathing pattern and posterior cricoarytenoid muscle activity.

Receptors responding to transmural pressure, airflow, and contraction of laryngeal muscles have been previously identified in the larynx. To assess the relative contribution of these three types of receptors to the reflex changes in breathing pattern and upper airway patency, we studied diaphragmatic (DIA) and posterior cricoarytenoid muscle (PCA) activity in anesthetized dogs during spontaneous breathing and occluded efforts with and without bypassing the larynx. Inspiratory duration (TI) was longer, mean inspiratory slope (peak DIA/TI) was lower, and PCA activity was greater with upper airway occlusion than with tracheal occlusion (larynx bypassed). Bilateral section of the superior laryngeal nerves eliminated these differences. When respiratory airflow was diverted from the tracheostomy to the upper airway the only change attributable to laryngeal afferents was an increase in PCA activity. These results confirm the importance of the superior laryngeal nerves in the regulation of breathing pattern and upper airway patency and suggest a prevalent role for laryngeal negative pressure receptors.

Airway Obstruction↗