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Although bronchoconstriction in response to C-fibre stimulation has been reported to be weak or absent in the newborn, pulmonary resistance and compliance have not been measured. We tested the hypothesis that capsaicin reflexly activates pulmonary efferent outflow to airway smooth muscle in the newborn. We measured breath-by-breath responses of inspiratory lung resistance (RLi) and dynamic compliance (CLdyn) in 13 newborn dogs and 4 newborn pigs during right heart injections of saline, capsaicin (25-50 micrograms/kg) and acetylcholine (ACh). Repeat capsaicin injections at 5 min intervals were made to test for desensitization in the newborn dog. All newborn dogs and 2 of 4 newborn pigs displayed a brisk bronchoconstriction; in the dog, RLi increased maximally by 97% +/- 13 (SE) and CLdyn decreased maximally by 32% +/- 2. In both species, initial capsaicin injections (CAP1) caused a long latency (time to peak heart rate 26.8 +/- 2 and 20 sec +/- 2.5) increase in heart rate (40% +/- 11 and 20.1% +/- 8.2 for the newborn dog and pig respectively). In the dog, but not the pig, capsaicin responses after the ACh trial (CAP2 and CAP3) caused a short latency bradycardia while the long latency tachycardia continued to be expressed in both species. The maximal changes in RLi and CLdyn, and the bradycardia, were reduced (i.e. desensitized) by 36%, 53% and 63% respectively if capsaicin injection was repeated within 5 min. Muscarinic blockade with atropine abolished the bronchoconstrictor and bradycardia responses to capsaicin but had no effect on the tachycardia. We conclude that the newborn possesses the neural circuitry to mount a bronchoconstrictor response to C-fibre stimulation. We speculate that the response is designed to reduce dead space and stabilize highly compliant airways of the newborn during the rapid shallow breathing that is typically associated with C-fibre stimulation.

We investigated the direct effects of efferent vagal activity on the distribution of inspired gas by stimulating the vagus nerve of one lung and measuring the topographic distribution of a radioactive tracer (133Xe) to both lungs. The distribution of inspired (133Xe) boli was measured with NaI scintillation detectors placed apex-base over each posterior lung of intubated, paralyzed, anesthetized dogs. In 7 supine dogs vagal stimulation reduced the distribution of rapidly insufflated 133Xe boli (flow greater than 2.5 L/s) to the test lung (P less than 0.02), but not when boli were insufflated slowly (flow less than 0.5 L/s), suggesting that vagal stimulation affects pulmonary gas distribution primarily by increasing airway resistance and not through changes in lung compliance. The effect of vagal stimulation on the regional apex-base distribution of inspired gas (greater than 2.5 L/s) was measured in 7 supine and 5 upright dogs. In the supine position, vagal stimulation did not change the uniform apex-base bolus distribution, whereas in the upright position less of the bolus was distributed to the middle and lower lung regions (P less than 0.043), compared to control measurements. This indicates that the regional effects of vagal stimulation on the distribution of inspired gas are uniform in the supine position, but that vagal stimulation alters the distribution of inspired gas when the apex-base pleural pressure gradient is increased.

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.

We compared the effects of hypoxia and hypercapnia on pulmonary mechanics in the newborn dog. Animals were anesthetized with a mixture of chloralose/urethane, paralyzed and ventilated with the chest open. Following an inflation to control volume history, mean inspiratory resistance (RLi) and dynamic compliance (CLdyn) were measured on a breath-by-breath basis during ventilation with control (FIO2 = 0.4), hypoxic (FIO2 = 0.1) and hypercapnic (FICO2 = 0.05) gas mixtures. Hypercapnia increased RLi 63% (n = 9) while hypoxia increased RLi in only 1/9 animals. Neither gas mixture changed CLdyn compared to control. The response to hypercapnia and the lone hypoxic response were eliminated by denervation of the airways by atropine administration or vagotomy. Following airway denervation hypoxia caused a small but statistically significant fall in CLdyn compared to the denervated control. These findings demonstrate that the newborn dog is capable of reflexly increasing bronchomotor tone and that vagal efferent innervation to the airways is functional at birth. Our data also suggest that in the newborn, central chemoreceptors are more effective than peripheral chemoreceptors in altering vagal tone to airway smooth muscle. Increased bronchomotor tone with hypercapnia may help to prevent dynamic compression of the airways.

Activity from afferents of respiratory origin was recorded from filaments of the vagus nerve in puppies 1-17 days old. Animals were anesthetized with a mixture of chloralose-urethane and artificially ventilated with the chest open. A total of 256 receptors were studied of which 96% were identified as slowly adapting mechanoreceptors (SARs) and 4% as rapidly adapting mechanoreceptors (RARs). Hence the newborn has fewer spontaneously active RARs than the adult. Thirty-five percent of SARs were located in the trachea and the remainder in the bronchi: a distribution similar to that found in the adult. The transpulmonary pressure (Ptp) threshold required for SAR activation was higher in the newborn than the adult for both tracheal (2.42 cm H2O vs 0.51 cm H2O) and bronchial 4.66 cm H2O vs 3.66 cm H2O) receptors. This resulted in less SAR activity at FRC in the puppy (16% of the total number of SARs in 1-17-day-old animals) compared to the adult (63%). In addition, the discharge frequency of tracheal and bronchial SARs, at any given Ptp, was lower in the newborn than in the adult dog. These data suggest that the newborn has considerably less volume-related feedback during the respiratory cycle compared to the adult.

Tracheal dimensions have been measured in a variety of newborn mammals ranging in body mass (M) from mouse to dolphin. Both tracheal diameter and tracheal length are nearly proportional to the cube root of M (M0.36 and M0.34, respectively). Tracheal volume is proportional to M1.07, and assuming that dead space volume (VD) is proportional to tracheal volume, VD is found to be proportional to FRC. Resting breathing frequency is proportional to M-0.21, therefore dead space ventilation (VD) can be calculated to be proportional to M0.86. This value is very close to the proportionality between oxygen consumption (VO2) and body weight reported in newborns (M0.88, Bartlett and Areson, 1977); since alveolar ventilation (VA) is proportional to VO2, VD is proportional to VA. From this, it can also be inferred that alveolar PCO2 and PO2 are nearly the same in newborns of different species.

The larynx has a rich sensory supply which is the main source of several respiratory reflexes. These reflexes, that influence both the patency of the upper airway and the pattern of breathing, are related to transmural pressure and/or airflow in the upper airway. Yet hardly any information is available on the response of laryngeal mechanoreceptors to transmural pressure and airflow. We recorded action potentials from single fibers separated from the superior laryngeal nerve of anesthetized dogs, breathing spontaneously either through a tracheostomy or the upper airway. The airway could be occluded above or below the larynx. On the basis of their behavior during tracheostomy breathing, upper airway breathing, tracheal occlusion and upper airway occlusion, laryngeal mechanoreceptors were classified as pressure receptors, flow receptors or 'drive' receptors (stimulated by the respiratory activity of upper airway muscles). Pressure receptors were encountered most frequently, representing 63.6% of our sample of 110 receptors, 'drive' receptors constituted 21.8% and flow receptors the remaining 14.6%. Our findings indicate that, even though the three types of receptors differ in sensory modality, they concur in exhibiting a predominant activity during inspiration. In fact, 65% of all receptors are active during eupneic inspiration. Moreover, their activity increases markedly during upper airway obstruction.

The static mechanical properties of the respiratory system have been studied in newborn mammals within the first two weeks of life, ranging in body size from rat to piglet, and compared to the corresponding adult. Animals were supine, paralyzed, and passively ventilated. The pressure-volume curves of the respiratory system and of the lung have been constructed by changing volume a known amount and measuring the tracheal pressure before and after opening the rib cage. In the newborns, the mean elastic recoil pressure of the lung at functional residual capacity (PLFRC) is 1.9 cm H2O with no clear correlation with body weight. The dry lung weight (LW)/body weight (BW) ratio is greater in newborns than in adults and progressively decreases with age. FRC (measured directly with the saline displacement method) is proportional to LW1.09 and BW1.03. In newborns, lung compliance per lung weight (CL/LW) is similar between species (Cl alpha LW1.07). Chest wall compliance per body weight is also constant (CW alpha BW1.00). By comparing the newborns with the corresponding adults we found that PLFRC is 35-57% of the adult value. FRC/LW in the newborn is less than or equal to the adult value, while FRC/BW is generally larger in the newborn. CL/LW is usually smaller in the newborn than in the adult while CW/BW is larger.

We studied the adaptive properties of tracheal and bronchial slowly adapting mechanoreceptors as an index of their dynamic responsiveness in newborn and adult dogs. The receptors studied exhibited a marked rate dependency in their adaptive characteristics: faster inflations leading to a higher adaptation, a behavior typically found in other mechanoreceptors. During inflations of comparable rates airway slowly adapting mechanoreceptors of newborn dogs reach initial firing rates (Fi) that are lower than those of adult dogs. These increments in activity appear to be reduced in proportion to their lower static discharge (Fs). Therefore when adaptation is represented as adaptation index (A.I. = (Fi - Fs)/Fi X 100), i.e., in relative terms, it does not differ between age groups. Tracheal and bronchial slowly adapting mechanoreceptors do not differ in their adaptation for either of the age groups. In conclusion, since the dynamic sensitivity is lower in newborns, it it cannot be a factor contributing to their higher breathing rate. Nevertheless, since newborns breathe faster than adults, the activation of their stretch receptors should be greater than it would have otherwise been, perhaps contributing to their faster rate of breathing.

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.

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.

We studied the response of tracheal slowly adapting stretch receptors (SARs), whose activity was recorded from the peripheral cut end of the right vagus nerve, in newborn and adult dogs during hyperoxic hypercapnia and isocapnic hypoxia. Tracheal receptors only were studied since it was possible to maintain the parasympathetic efferent supply partially intact (contralateral vagus nerve and superior laryngeal nerve). The animals were anesthetized and passively ventilated with the chest open. A stimulatory effect was found in 9 out of 20 puppies for hypercapnia and in 3 out of 10 for hypoxia. The maximum amount of stimulation ranged from 114 to 556% of the control discharge for hypercapnia and from 110 to 387% for hypoxia. In the adult dog CO2 stimulated tracheal SARs in 11 out of 16 dogs (103-404% control) while hypoxia stimulated SARs in 9 out of 13 animals (109-268% control). The stimulatory effect was greater during expiration and, for hypercapnia, decreased in intensity with time. This excitatory action was eliminated by cold block of the contralateral vagus nerve or atropine administration, suggesting that the stimulation was mediated by smooth muscle contraction. These findings support the notion that airway stretch receptors are activated not only by passive distension of the airways, but also by an active contraction of the tracheobronchial smooth muscle.