Ventilatory and timing parameters in normal horses at rest up to age one year.

The purpose of the study was to document the developmental changes in the ventilatory and timing parameters associated with quiet breathing at rest in awake, standing horses during the first year post partum. Tidal volume (VT), breathing frequency, airflow, mechanical timing intervals and minute ventilation (VE) were measured serially in foals age 24 h-1 year. In the growing foal, VE increased due to a progressive rise in VT, in spite of a pronounced decrease in respiratory frequency. When normalised to body weight (bwt), VE/kg declined with maturation in a curvilinear fashion, from mean +/- s.d. 848 +/- 231 ml/min/kg in the 24 h-old foal, to 155 +/- 15 ml/kg/min in the 1-year-old foal. Tidal volume normalised to bwt remained relatively constant during the study period, with the exception that at age 3 weeks and from 2-6 months, VT/kg was significantly lower than the value recorded at age 1 week. The decrease in frequency resulted from prolongation of both inspiratory (TI) and expiratory (TE) time but there was a disproportionately larger increase in TE compared to TI, which resulted in a significantly lower ratio of TI/TE in older foals. The allometric equation relating VT to bwt suggested that lung growth in the horse is dysanaptic, with increases in overall body size exceeding lung growth in the maturing foal during the first year post partum.

Changes in breathing pattern in the normal horse at rest up to age one year.

Changes in pattern of airflow, sequence of respiratory muscle activation and generated pressures were measured serially in a group of foals during the first year post partum, in order to describe the maturation of the equine breathing pattern. In neonatal foals, inspiration and expiration were both primarily active and airflow pattern was essentially monophasic. By age 1 year, foals displayed essentially the same breathing pattern previously described in adult horses, utilising a combination of active and passive inspiration and expiration to breathe around, rather than from, the relaxation volume of the respiratory system (Vrx). A strong temporal relationship during growth was found between the timing of changes observed in airflow pattern and in the neuromuscular strategy of breathing. The transition to the adult breathing pattern appeared to involve a time delay in activation of both inspiratory and expiratory muscle groups, establishing a passive and active component to both inspiration and expiration. Throughout the study period, concurrent with the increase in delay of abdominal muscle activation, the expiratory flow pattern became progressively more biphasic in appearance. The time of appearance of a consistent biphasic inspiratory flow pattern was considerably later, at approximately age 1 year and coincided with the appearance of a delay in inspiratory muscle activation. From our results, we conclude that the transition from the neonatal to the adult breathing strategy in the horse appears not to be induced by the time course of chest wall stiffening during maturation. While changes in relative body proportions and size of abdominal contents during growth may influence the transition in breathing, our results also indicate that respiratory control mechanisms play an essential role in the expression of the polyphasic breathing pattern.

Respiratory muscle activities after birth in asphyxiated preterm lambs.

Laryngeal and pump muscle activities are important in the establishment and maintenance of functional residual capacity (FRC) after birth. The aim of this study was to determine the expiratory mechanisms by which laryngeal and diaphragmatic activities achieve the increments in FRC postnatally. Wire electrodes were placed in: the laryngeal abductor, a major laryngeal adductor, the inferior pharyngeal constrictor and the diaphragm of six fetal sheep. The lambs were delivered prematurely by cesarean section and a face mask with a pneumotachograph applied. A grunting respiratory pattern was characterized by severe expiratory airflow retardation, associated with laryngeal adductor activity. In grunting breaths, minimal volume loss at end-expiration and incremental increases in FRC occurred when the onset of diaphragmatic activity preceded the onset of laryngeal muscle activities associated with laryngeal opening. Thus the timing order of laryngeal and diaphragmatic muscle activities near end-expiration is a determinant of increments in FRC.

Respiratory mechanics of the horse during the first year of life.

This study investigated the developmental changes in the mechanical properties of the respiratory system in growing horses. Pulmonary mechanics and lung volumes were serially measured in anesthetized foals during the first year of life. Quasi-static pressure-volume curves were generated, and functional residual capacity (FRC) was measured using a closed nitrogen equilibration technique. At birth, chest wall compliance normalized to body weight was substantially less than that reported in other less precocious newborn species, while lung compliance normalized to body weight was similar to values reported for other species. Characteristics of the transition from the neonatal to adult respiratory system in the foal included a decrease in the ratios of chest wall to lung compliance (Cw/CL) and the unstressed volume of the chest wall to TLC, and a constant FRC/TLC throughout most of the study period. The somatic growth of the foal and its respiratory system were uneven processes, with increases in lung volume lagging increases in overall body size.

Laryngeal and diaphragmatic muscle activities and airflow patterns after birth in premature lambs.

The nature and control of early neonatal respiratory patterns were determined in 10 premature, asphyxiated lambs. Severe retardation of early expiratory airflow (braking) characterized an initial pattern (A), but was absent in a final one (B). During a transition pattern (pattern T), pattern A and B airflow types occurred. Close temporal relationships between the airflow patterns and posterior cricoarytenoid (PCA), thyroarytenoid (TA), and diaphragm (D) integrated muscle activities were demonstrated quantitatively. Specifically, in pattern A, the duration of braked expiratory airflow was related to the durations of TA burst activity and the absence of PCA burst activity (r2 = 0.99). In pattern A, pH, but not arterial PCO2 or arterial PO2, differed from that in patterns T and B [7.01 +/- 0.14 (A), 7.11 +/- 0.12 (T), 7.19 +/- 0.08 (B) (P < 0.03)]. Within-breath airflow and respiratory muscle activity relationships and differences in neural and mechanical respiratory timing intervals between patterns suggested that neural feedback was important in the control of central pattern generation. Thus activities of PCA, TA, and D shape the early neonatal airflow patterns and are influenced mainly by neuromechanical, and not chemical, feedback.

Laryngeal and pump muscle activities during CO2 breathing in neonates.

Term human newborns were challenged with a 2-3% CO2 gas mixture during quiet sleep. A common ventilatory response, consisting of increased tidal volume with no change in respiratory frequency or timing, was observed in all eight subjects. Minute ventilation and mean inspiratory and expiratory flow rates were elevated in all eight subjects [38 +/- 8 (SE), 38 +/- 22, and 39 +/- 9%, respectively]. Diaphragm, intercostal, and posterior cricoarytenoid (PCA) muscle activities during inspiration were increased in four of eight, six of eight, and seven of eight subjects, respectively Changes in intercostal and PCA muscle activities correlated with changes in inspiratory flow rates (r = 0.77 and 0.66, respectively). Diaphragmatic braking of expiratory airflow varied between subjects during room air breathing and did not change in six subjects with CO2 breathing. The remaining two subjects increased postinspiratory inspiratory diaphragmatic activity. Baseline expiratory PCA activity was augmented with CO2 breathing in six of eight subjects and correlated with increases in mean expiratory airflow (r = 0.76). The newborn infant is capable of using a variety of breathing strategies to augment tidal volume and minute ventilation, and control of the upper airway appears to be critical in modulating airflow during CO2 breathing.

Developmental changes in sequential activation of laryngeal abductor muscle and diaphragm in infants.

In animals and human adults, upper airway muscle activity usually precedes inspiratory diaphragm activity. We examined the interaction of the posterior cricoarytenoid muscle (PCA), which abducts the larynx, and the diaphragm (DIA) in the control of airflow in newborn infants to assess the effect of maturation on respiratory muscle sequence. We recorded tidal volume, airflow, and DIA and PCA electromyograms (EMG) in 12 full-term, 14 premature, and 10 premature infants with apnea treated with aminophylline. In most breaths, onset of PCA EMG activity preceded onset of DIA EMG activity (lead breaths). In all subjects, we also observed breaths (range 6-61%) in which PCA EMG onset followed DIA EMG onset (lag breaths). DIA neural inspiratory duration and the neuromechanical delay between DIA EMG onset and inspiratory flow were longer in lag than in lead breaths (P < 0.05 and P < 0.01, respectively). The frequency of lag breaths was greater in the premature infants [33 +/- 4% (SE)] than in either the full-term infants (21 +/- 3%, P < 0.03) or the premature infants with apnea treated with aminophylline (16 +/- 2%, P < 0.01). We conclude that the expected sequence of onset of PCA and DIA EMG activity is frequently disrupted in newborn infants. Both maturation and respiratory stimulation with aminophylline improve the coordination of the PCA and DIA.

Spirometric and endoscopic evaluation of airway collapse in infants with bronchopulmonary dysplasia.

We evaluated eight infants with bronchopulmonary dysplasia (BPD) at ages from 2 to 13 months who had repeated episodes of clinical respiratory deterioration associated with agitation. These episodes limited further weaning from ventilation or necessitated recurrent intubation and reinstitution of ventilation. All infants underwent spirometric evaluation and six also had endoscopic examination during simulated agitation episodes (elicited by toe pinching). All babies were found to have a very prolonged near zero expiratory airflow pattern, accompanied by vigorous diaphragmatic and abdominal muscle activity and rapid development of hypoxia. Six patients had endoscopically documented tracheal collapse under the same simulated circumstances. The episodes ceased with calming or sedation of the infants.

Pulmonary vascular reactivity of the newborn pony foal.

Adult ponies develop pulmonary hypertension at altitude (Bisgard, Orr and Will 1975), but the neonatal response to acute hypoxaemia is unknown. Seven foals aged five days were instrumented with a systemic and a Swan-Ganz pulmonary artery catheter while anesthetised and intubated. Cardiac index, pulmonary (PAP) and systemic (SAP) vascular pressures were measured as the foals breathed gas mixtures with FI02 of 8 to 94 per cent. Because foramen ovale or ductus arteriosus shunts might have altered thermodilution cardiac index measurements in the stressed foals, the ratio, PAP/SAP was calculated to define relative circulatory reactivity. Three foals, two of which were full siblings, had very marked elevation of PAP/SAP from 0.6 to 1.41 at low inspired oxygen tensions. Four different foals attained maximal PAP/SAP of only 0.2 to 0.92 at similarly low oxygen tensions (P less than 0.0001). Thus, pulmonary vascular reactivity to ventilatory hypoxaemia varied greatly in pony foals of the same age. The exaggerated reactivity in related foals suggested that, as in cattle, a genetic predisposition to develop reactive pulmonary hypertension under hypoxaemic stress may exist.

Responses of pulmonary vagal mechanoreceptors to high-frequency oscillatory ventilation.

The discharge of 57 slowly adapting pulmonary stretch receptors (PSR's) and 16 rapidly adapting receptors (RAR's) was recorded from thin vagal filaments in anesthetized dogs. The receptors were localized and separated into three groups: extrathoracic tracheal, intrathoracic tracheal, and intrapulmonary receptors. The influence of high-frequency oscillatory ventilation (HFO) at 29 Hz on receptor discharge was analyzed by separating the response to the associated shift in functional residual capacity (FRC) from the oscillatory component of the response. PSR activity during HFO was increased from spontaneous breathing (49%) and from the static FRC shift (25%). PSR activity during the static inflation was increased 19% over spontaneous breathing. RAR activity was also increased with HFO. These results demonstrate that 1) the increased activity of PSR and RAR during HFO is due primarily to the oscillating action of the ventilator and secondarily to the shift in FRC associated with HFO, 2) the increased PSR activity during HFO may account for the observed apneic response, and 3) PSR response generally decreases with increasing distance from the tracheal opening.

Control of inspiratory duration in premature infants.

We used single-breath mechanical loads and airway occlusions in premature infants to determine whether maturation influences the reflex control of inspiratory duration. We measured flow, volume, airway pressure, and surface diaphragmatic electromyogram (EMG) in 10 healthy preterm infants [33 +/- 1 (SD) wk gestation], 2-7 days of age. Three resistive and two elastic loads and occlusions were applied to the inspiratory outlet of a two-way respiratory valve. Application of all loads resulted in inspired volumes significantly decreased from control (P less than 0.001), and these decreases were progressive with increasing loads. Inspiratory duration (TI) was prolonged from control by all loads and occlusions when measured from the diaphragmatic EMG (neural TI) and by all but the smaller elastic load when measured from the flow tracing (mechanical TI). Similar decreases in inspired volume at the end of neural TI produced by application of both elastic and resistive loads resulted in comparable prolongation of neural TI. In contrast, for comparable volume decrements, resistive loading prolonged mechanical TI more than elastic loading (P less than 0.001). Mechanical and neural TI values of the breath after the loaded breath were unchanged from control values. Comparison of the neural volume-timing relationship in premature infants with our data in full-term infants suggests that the strength of the timing response to similar relative decrements in inspired volume is comparable. We conclude that reflex control of neural TI in premature infants depends on the magnitude of inspired volume and is independent of the volume trajectory.(ABSTRACT TRUNCATED AT 250 WORDS)

Posterior cricoarytenoid and diaphragm activities during tidal breathing in neonates.

To investigate airflow regulation in newborn infants, we recorded airflow, volume, diaphragm (Di), and laryngeal electromyogram (EMG) during spontaneous breathing in eight supine unsedated sleeping full-term neonates. Using an esophageal catheter electrode, we recorded phasic respiratory activity consistent with that of the principal laryngeal abductors, the posterior cricoarytenoids (PCA). Sequential activation of PCA and Di preceded inspiration. PCA activity typically peaked early in inspiration followed by either a decrescendo or tonic EMG activity of variable amplitude during expiration. Expiratory airflow retardation, or braking, accompanied by expiratory prolongation and reduced ventilation, was commonly observed. In some subjects we observed a time interval between PCA onset and a sudden increase in expiratory airflow just before inspiration, suggesting that release of the brake involved an abrupt loss of antagonistic adductor activity. Our findings suggest that airflow in newborn infants is controlled throughout the breathing cycle by the coordinated action of the Di and the reciprocal action of PCA and laryngeal adductor activities. We conclude that braking mechanisms in infants interact with vagal reflex mechanisms that modulate respiratory cycle timing to influence both the dynamic maintenance of end-expiratory lung volume and ventilation.

Breathing strategy of the adult horse (Equus caballus) at rest.

To investigate the mechanism underlying the polyphasic airflow pattern of the equine species, we recorded airflow, tidal volum, rib cage and abdominal motion, and the sequence of activation of the diaphragm, intercostal, and abdominal muscles during quiet breathing in nine adult horses standing at rest. In addition, esophageal, abdominal, and transdiaphragmatic pressures were simultaneously recorded using balloon-tipped catheters. Analysis of tidal flow-volume loops showed that, unlike humans, the horse at rest breathes around, rather than from, the relaxed volume of the respiratory system (Vrx). Analysis of the pattern of electromyographic activities and changes in generated pressures during the breathing cycle indicate that the first part of expiration is passive, as in humans, with deflation toward Vrx, but subsequent abdominal activity is responsible for a second phase of expiration: active deflation to below Vrx. From this end-expiratory volume, passive inflation occurs toward Vrx, followed by a second phase of inspiration: active inflation to above Vrx, brought about by inspiratory muscle contraction. Under these conditions the abdominal muscles appear to share the principal pumping duties with the diaphragm. Adoption of this breathing strategy by the horse may relate to its peculiar thoracoabdominal anatomic arrangement and to its very low passive chest wall compliance. We conclude that there is a passive and active phase to both inspiration and expiration due to the coordinated action of the respiratory pump muscles responsible for the resting adult horse's biphasic inspiratory and expiratory airflow pattern. This unique breathing pattern perhaps represents a strategy of minimizing the high elastic work of breathing in this species, at least at resting breathing frequencies.

Control of laryngeal muscle activity in preterm infants.

Control of upper airway muscles, such as those in the larynx, appears important for optimizing airflow patterns during normal respiration. Electromyograms (EMGs) of the laryngeal (LAR) area and diaphragm (DIA) were recorded with esophageal and skin electrodes, respectively, in 12 unsedated sleeping preterm infants during changes in chemical and mechanical feedback. Onset of phasic inspiratory LAR EMG preceded both DIA EMG and inspiratory airflow by 70 +/- 60 and 180 +/- 80 ms, respectively. Inhalation of 4% CO2 increased both peak LAR and DIA EMGs but did not alter their temporal relationships. End expiratory occlusion prolonged both LAR (600 +/- 120 to 930 +/- 290 ms, p less than 0.05) and DIA EMGs (690 +/- 180 to 940 +/- 270 ms, p less than 0.005) as well as mechanical inspiratory time. Early braking of expiratory flow was accompanied by persistence of DIA EMG into the expiratory phase, while termination of mid- to late expiratory braking was associated with onset of the LAR EMG of the subsequent inspiration. We conclude that respiratory activity of the LAR EMG is altered by both chemical and mechanoreceptor stimulation. Furthermore, simultaneous recording of LAR and DIA EMGs suggests that upper airway and chest wall muscles have different effects on expiratory flow patterns in human infants.

Regulation of end-expiratory lung volume during sleep in premature infants.

To investigate the regulation of end-expiratory lung volume (EEV) in premature infants, we recorded airflow, tidal volume, diaphragm electromyogram (EMG), and chest wall displacement during sleep. In quiet sleep, EEV during breathing was 10.8 +/- 3.6 (SD) ml greater than the minimum volume reached during unobstructed apneas. In active sleep, no decrease in EEV was observed during 28 of 35 unobstructed apneas. Breaths during quiet sleep had a variable extent of expiratory airflow retardation (braking), and inspiratory interruption occurred at substantial expiratory flow rates. During active sleep, the expiratory flow-volume curve was nearly linear, proceeding nearly to the volume axis at zero flow, and diaphragm EMG activity terminated near the peak of mechanical inspiration. Expiratory duration (TE) and inspiratory duration (TI) were significantly shortened in quiet sleep vs. active sleep although tidal volume was not significantly different. In quiet sleep, diaphragmatic braking activity and shortened TE combined to maintain EEV during breathing substantially above relaxation volume. In active sleep, reduced expiratory braking and prolongation of TE resulted in an EEV that was close to relaxation volume. We conclude that breathing strategy to regulate EEV in premature infants appears to be strongly influenced by sleep state.

Respiratory mechanics and breathing pattern in the neonatal foal.

Breathing pattern, respiratory muscle activation pattern, lung volumes and volume-pressure characteristics of the respiratory system of normal, term, neonatal foals on Days 2 and 7 of age were determined to test the hypothesis that the foal actively maintains end-expiratory lung volume (EEV) greater than the relaxation volume of the respiratory system (Vrx) because of a highly compliant chest wall. Breathing pattern was measured in the awake, unsedated foal during quiet breathing in lateral and standing positions. The typical neonatal foal breathing pattern was characterized by a monophasic inspiratory and expiratory flow pattern. Both inspiration and expiration were active, with onset of Edi activity preceding onset of inspiratory flow, and phasic abdominal muscle activity detectable throughout most of expiration. No evidence was found to support the hypothesis that the normal, term neonatal foal actively maintains EEV greater than Vrx. In the neonatal foal, normalized lung volume and lung compliance values were similar to those reported for neonates of other species, while normalized chest wall compliance was considerably lower. We conclude that the chest wall of the term neonatal foal is sufficiently rigid to prevent a low Vrx. This characteristic probably prevents the foal from having to use a breathing strategy which maintains an EEV greater than Vrx.

Reflex control of inspiratory duration in newborn infants.

We applied graded resistive and elastic loads and total airway occlusions to single inspirations in six full-term healthy infants on days 2-3 of life to investigate the effect on neural and mechanical inspiratory duration (TI). The infants breathed through a face mask and pneumotachograph, and flow, volume, airway pressure, and diaphragm electromyogram (EMG) were recorded. Loads were applied to the inspiratory outlet of a two-way respiratory valve using a manifold system. Application of all loads resulted in inspired volumes decreased from control (P less than 0.001), and changes were progressive with increasing loads. TI measured from the pattern of the diaphragm EMG (TIEMG) was prolonged from control by application of all elastic and resistive loads and by total airway occlusions, resulting in a single curvilinear relationship between inspired volume and TIEMG that was independent of inspired volume trajectory. In contrast, when TI was measured from the pattern of airflow, the effect of loading on the mechanical time constant of the respiratory system resulted in different inspired volume-TI relationships for elastic and resistive loads. Mechanical and neural inspired volume and duration of the following unloaded inspiration were unchanged from control values. These findings indicate that neural inspiratory timing in infants depends on magnitude of phasic volume change during inspiration. They are consistent with the hypothesis that termination of inspiration is accomplished by an "off-switch" mechanism and that inspired volume determines the level of vagally mediated inspiratory inhibition to trigger this mechanism.

Preliminary studies on the measurement of conjunctival oxygen tension in the foal.

The capability of a transconjunctival oxygen monitoring system to provide an accurate and reliable means of observing arterial oxygenation trends was evaluated in 12 horse and pony foals between 5 and 20 days of age. Ten of the foals were anesthetized with isoflurane in oxygen and nitrous oxide, and 2 foals were conscious. Inspired oxygen concentration was manipulated by differing proportions of oxygen and nitrous oxide in the fresh gas supplied to the breathing circuit. With arterial oxygen tension values ranging from less than 20 to greater than 400 mm of Hg, all foals had significant positive correlations between arterial and conjunctival oxygen tensions (P less than 0.001). Although the system seemed accurate and reliable, monitoring oxygenation in awake and mobile foals may require a ring conformer made to fit the foal's eye.

Pulmonary physiology of the ferret and its potential as a model for inhalation toxicology.

Physiological measurements were made from anesthetized, tracheotomized, supine male ferrets. Six animals weighing 576 +/- 12 g, had tidal volumes (Vt) of 6.06 +/- 0.30 ml, respiratory frequencies (f) of 26.7 +/- 3.9 min(-1), dynamic lung compliance (CDYN) of 2.48 +/- 0.21 ml cmH2O(-1), pulmonary resistance (RL) of 22.56 +/- 1.61 cmH2O L(-1) sec. Pressure-volume curves from nine ferrets (including the above six) revealed almost infinitely compliant chest walls so that lung and total respiratory system curves were essentially the same. Total lung capacity (TLC) (89 +/- 5 ml) and functional residual capacity (FRC) (17.8 +/- 2.0 ml) were determined by gas freeing the lungs in vivo. The TLC of these ferrets was about the same as in 2.5 kg rabbits. Maximum expiratory flow-volume curves showed peak flows of 10.1 vital capacities (VC) sec(-1) at 75% VC and flows of 8.4 and 5.4 VC sec(-1) at 50% and 25% VC. No particular problems were encountered in making these measurements using conventional techniques available in laboratories capable of making pulmonary function measurements on rats and guinea pigs. Preliminary studies of airways reactivity showed equal increases in pulmonary resistance in response to equivalent challenges of aerosolized carbachol and histamine. Light and electron microscopic studies showed that the airways of ferrets are even more like those of humans than are the dog's. The ease with which physiological measurements can be made and the favorable aspects of the lung anatomy indicate the ferret may be more useful, as well as less expensive, than the dog for use in studies of pulmonary physiology and inhalation toxicology.

Reflex control of expiratory duration in newborn infants.

We investigated the effect on expiratory duration (TE) of application of graded resistive and elastic loads and total airway occlusions to single expirations in 9 full-term healthy infants studied on the 2nd or 3rd day of life. The infants breathed through a face mask and pneumotachograph, and flow, volume, airway pressure, and diaphragm electromyogram (EMG) were recorded. Loads were applied to the expiratory outlet of a two-way respiratory valve using a manifold system. Application of all loads resulted in expired volumes (VE) decreased from control (P less than 0.05), and changes were progressive with increasing loads. As VE became smaller, end-expiratory volume (EEV) became greater. TE, measured either from the pattern of airflow or airway pressure, or from diaphragm EMG activity, progressively increased with increasing loads and was greatest with total occlusions (P less than 0.05, compared with control). Resistive loading resulted in a greater accumulated VE history than elastic loading to the same EEV. For equivalent changes in EEV, TE was more prolonged with resistive than with elastic loading. Expiratory loading did not change the inspiratory duration determined from the diaphragm EMG activity of the breath immediately following each loaded expiration. These findings in infants are consistent with an integrative neural mechanism that modulates TE in response to the accumulated VE history, including both EEV and rate of lung deflation.