Oommen P. Mathew

Breathing patterns of preterm infants during bottle feeding: Role of milk flow

Milk flow achieved during feeding may contribute to the ventilatory depression observed during nipple feeding. One of the important determinants of milk flow is the size of the feeding hole. In the first phase of the study, investigators compared the breathing patterns of 10 preterm infants during bottle feeding with two types of commercially available (Enfamil) single-hole nipples: one type designed for term infants and the other for preterm infants. Reductions in ventilation, tidal volume, and breathing frequency, compared with prefeeding control values, were observed with both nipple types during continuous and intermittent sucking phases; no significant differences were observed for any of the variables. Unlike the commercially available, mechanically drilled nipples, laser-cut nipple units showed a markedly lower coefficient of variation in milk flow. In the second phase of the study, two sizes of laser-cut nipple units, low and high flow, were used to feed nine preterm infants. Significantly lower sucking pressures were observed with high-flow nipples as compared with low-flow nipples. Decreases in minute ventilation and breathing frequency were also significantly greater with high-flow nipples. These results suggest that milk flow contributes to the observed reduction in ventilation during nipple feeding and that preterm infants have limited ability to self-regulate milk flow.

Laryngeal pressure receptors

We studied the response characteristics of laryngeal pressure receptors in anesthetized dogs, breathing through a tracheal cannula, by recording single unit action potentials from the peripheral cut end of the internal branch of the superior laryngeal nerve. The larynx, with the rest of the upper airway, was isolated and cannulated separately for the application of distending and collapsing pressures. We identified receptors responding to either negative or positive pressure and a few responding to both. All these receptors showed a marked dynamic sensitivity and had the characteristics of slowly adapting mechanoreceptors. The majority of pressure receptors were active at zero transmural pressure and the gain of their response to pressure was higher at lower values, suggesting a role for these receptors in eupnea. Reflex alterations in breathing pattern and upper airway muscle activity during upper airway pressure changes, previously reported, are presumably mediated by the receptors described here. Moreover, these receptors may play a role in certain pathological states, such as obstructive sleep apnea, in which the upper airway is transiently subjected to large collapsing pressure.

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.

Effect of upper airway negative pressure on respiratory timing

The effects of upper airway negative pressure on respiratory timing and respiratory muscle activity were investigated in 13 urethane-pentobarbital anesthetized adult rabbits. Diaphragm and upper airway muscle EMGs were recorded with fine wire electrodes. The upper airway was converted into a closed system and negative pressure changes were made at will with a syringe attached to a laryngeal cannula. Both inspiratory and expiratory durations (Ti and Te) were prolonged during the negative pressure trials. Maximal prolongation occurred on the first experimental breath for Te and on second breath for Ti. Decreased effects were seen during maintained negative pressures. Peak diaphragm EMG and average slope of diaphragm EMG decreased during these trials. Diaphragmatic apnea (Te greater than or equal to 5 sec) occurred in 15% of trials. In some of these trials apnea lasted as long as the negative pressure stimulus whereas in others spontaneous breathing resumed after a period of apnea. Phasic upper airway muscle activity occurred during diaphragmatic apnea in most of these trials. The superior laryngeal nerve section markedly reduced the effects of negative pressure, indicating that its afferents primarily mediate this response. Our results suggest that upper airway negative pressure acts centrally on both inspiratory and expiratory timing as well as on the motor output of thoracic and upper airway respiratory muscles.

Respiratory afferent activity in the superior laryngeal nerves

This study evaluates the afferent activity in the superior laryngeal nerve (SLN) during breathing as well as during occluded inspiratory efforts. Experiments were performed in 11 anesthetized and spontaneously breathing dogs. Electroneurographic activity was recorded from the peripheral cut end of the SLN and, in 3 dogs, also from the contralateral vagus nerve. A tracheal cannula with a side arm allowed the bypass of the larynx during breathing and occluded efforts. A clear inspiratory modulation was present in all experimental conditions. Both peak and duration of the SLN activity decreased (87% and 89%) when breathing was diverted from the upper airway to the tracheostomy. Peak and duration of the SLN activity (as % of upper airway breathing) increased during occluded efforts; however, the increase was greater when the larynx was not by-passed (peak = 118% vs 208%, duration = 143% vs 178%). Section of the ipsilateral recurrent laryngeal nerve reduced the inspiratory modulation. Vagal afferent activity increased equally during tracheostomy and upper airway breathing and decreased markedly during tracheal and upper airway occlusions. Our results indicate that collapsing pressure in the larynx is the major stimulus in activating laryngeal afferents.

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.

Carbon dioxide-responsive laryngeal receptors in the dog

The purpose of this study was to relate the carbon dioxide (CO2) response of laryngeal receptors to their behavior during the breathing cycle (i.e. their response to transmural pressure changes, laryngeal movement or decreases in temperature) or during exposure to irritant stimuli (water or cigarette smoke). In 9 anesthetized mongrel dogs breathing spontaneously through a tracheostomy, unit activity from the superior laryngeal nerve was recorded while warmed and humidified gas mixtures (air or 10% CO2 in O2) were passed, for 1 min, through the functionally isolated upper airway in the expiratory direction. None of the 10 cold receptors studied were affected by CO2. Eleven of 20 laryngeal non-modulated mechano-receptors were stimulated (from 0.3 to 1.6 imp/sec) by exposure to CO2. These CO2-responsive receptors were also stimulated by known irritant stimuli (cigarette smoke, water), although not all receptors which responded to these irritants were stimulated by CO2. Twelve of 33 respiratory-modulated receptors were affected by CO2; 4 were stimulated and 8 inhibited. Receptors inhibited by CO2 were also inhibited by negative pressure while receptors stimulated by CO2 were also stimulated by negative pressure. These results show that CO2-responsive laryngeal receptors are not specialized endings. Although it is not clear to what extent each separate group of laryngeal receptors is involved, each may contribute to the reflex bradypnea which has been observed during exposure of the upper airway to elevated levels of CO2. However, the importance of CO2-responsive laryngeal receptors in physiological conditions remains unclear.

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.

Respiratory activity in the superior laryngeal nerve of the rabbit

We studied the respiratory modulation of laryngeal afferents and their response to transmural pressure in 24 anesthetized, spontaneously breathing rabbits. Laryngeal afferent activity has a predominant inspiratory augmentation during tracheal breathing or tracheal occlusion that can be accounted for by the respiratory movement transmitted to the larynx through the trachea. During upper airway breathing or upper airway occlusion SLN afferent activity increases in expiration and decreases in inspiration. This respiratory modulation is due to changes in upper airway pressure (Pua). In fact, positive pressure stimulates SLN afferent activity, while negative pressure inhibits it. Mechanical restriction of epiglottal movement reduced the response to Pua changes during upper airway occlusion and application of maintained positive (0.1-0.5 kPa) and negative (-0.1 to -0.5 kPa) pressures (P less than 0.005). Furthermore, surgical removal of epiglottis decreased the baseline activity of SLN to 16.5% of control. These experiments suggest that in the rabbit the epiglottis is the main source of SLN afferent activity and that its displacement, due to changes in Pua, is the most important factor for modulating SLN activity. Most of the laryngeal receptors showed an inspiratory augmentation with tracheal breathing and occlusion, were stimulated by positive pressure and inhibited by negative pressure, reflecting the behavior observed in the whole nerve.

Response of laryngeal receptors to water solutions of different osmolality and ionic composition.

Water-responsive laryngeal receptors with fibres in the superior laryngeal nerve were studied to characterize the specific physicochemical properties of aqueous solutions that activate these endings. The responses to water (37 degrees C) of 141 receptors were studied in 39 anaesthetized dogs breathing through a tracheostomy with the larynx functionally isolated. Of the 89 receptors stimulated by water, 53 were also challenged with isosmotic (275-315 mOsm) solutions of dextrose and sodium gluconate at 37 degrees C. Receptors that only responded to water (n = 31) with a long delay, long duration discharge were generally respiratory modulated. On the other hand, laryngeal receptors that responded to all test solutions (n = 22) with a short delay, short duration discharge were generally not respiratory modulated. We conclude that the former type of receptor responds to lower osmolality, whereas the latter responds to the lack of chloride ions in the test solutions. These two types of receptor may be responsible for the cough and bronchoconstriction induced by inhaled aerosols of different osmolalities and ionic compositions.