Adaptation to reflex effects of prolonged lung inflation

Adaptation to the reflex effects of sustained changes in lung volume on inspiratory duration (TI), expiratory duration (TE), and the phrenic neurogram was examined. Test inflations in gallamine-paralyzed dogs anesthetized with pentobarbital sodium were made during a 6-min trial while the animal was not ventilated: 2 min at functional residual capacity (FRC), 2 min at elevated airway pressure, and 2 min back at FRC. The dogs were hyperoxygenated and arterial PCO2 was kept constant by an infusion of tris (hydroxymethyl) aminomethane. The maintained inflations produced minimal changes in TI. On return to FRC, TI was prolonged in proportion to the magnitude of the prior inflation. In contrast, inflation produced marked prolongation of TE, which then adapted back toward preinflation values. On return to FRC, TE shortened initially to values below control. This shortening increased with greater prior lung inflations. The times to reestablish steady-state values upon return to FRC differed for TI (14.8 +/- 4.6 s) and TE (33.8 +/- 12.7 s). The magnitude of the phrenic neurogram at a fixed time from onset of inspiration and its slope were unchanged with inflation. These results indicate that respiratory phase durations are influenced not only by pulmonary afferent input within each respiratory cycle but also by prior vagal afferent activity that engages central processes with long, although different, time constants. Afferent input to the slow central process controlling TI is not gated to only one phase of the respiratory cycle.     

Ventilatory responses to lung inflation and arterial CO2 in halothane-anesthetized dogs

Hypercapnia attenuates the effects of static airway pressure (Paw) on phrenic burst frequency (f) and the expiratory duration (TE) in chloralose-urethan-anesthetized dogs. Surgical removal of the carotid bodies abolishes this interaction. Since halothane anesthesia in hyperoxia greatly impairs peripheral chemoreflexes, experiments were conducted to determine whether hypercapnia would attenuate the effects of Paw on f and TE in halothane-anesthetized dogs (approximately 1.5 minimum alveolar concentration). Integrated activity of the phrenic nerve was monitored as a function of Paw (2-12 cmH2O) in a vascularly isolated left lung at varied levels of arterial PCO2 (PaCO2; 38-80 Torr) controlled by inspired gas concentrations ventilating the denervated but perfused right lung. Halothane was administered only to the right lung. The results were as follows: 1) integrated phrenic amplitude increased with PaCO2 but was unaffected by Paw; 2) f decreased as Paw increased but was not affected by PaCO2; 3) the inspiratory duration (TI) increased as PaCO2 increased but was unaffected by Paw; 4) TE increased as Paw increased but was unaffected by PaCO2; and 5) there was no phrenic response to intravenous sodium cyanide (50-100 micrograms/kg). Thus, unlike chloralose-urethan-anesthetized dogs, hypercapnia does not attenuate the effect of lung inflation on f or TE in halothane-anesthetized dogs. Furthermore, hypercapnia increases TI during halothane anesthesia, an effect found after carotid denervation but not found in intact chloralose-urethan-anesthetized dogs. It is suggested that these differences between chloralose-urethan- and halothane-anesthetized dogs may be due to functional carotid chemoreceptor denervation by halothane.     

Phasic pulmonary stretch receptor feedback modulates both eupnea and gasping in an in situ rat preparation

The perfused in situ juvenile rat preparation produces patterns of phrenic discharge comparable to eupnea and gasping in vivo. These ventilatory patterns differ in multiple aspects, including most prominently the rate of rise of inspiratory activity. Although we have recently demonstrated that both eupnea and gasping are similarly modulated by a Hering-Breuer expiratory-promoting reflex to tonic pulmonary stretch, it has generally been assumed that gasping was unresponsive to afferent stimuli from pulmonary stretch receptors. In the present study, we recorded eupneic and gasplike efferent activity of the phrenic nerve in the in situ juvenile rat perfused brain stem preparation, with and without phrenic-triggered phasic pulmonary inflation. We tested the hypothesis that phasic pulmonary inflation produces reflex responses in situ akin to those in vivo and that both eupnea and gasping are similarly modulated by phasic pulmonary stretch. In eupnea, we found that phasic pulmonary inflation decreases inspiratory burst duration and the period of expiration, thus increasing burst frequency of the phrenic neurogram. Phasic pulmonary inflation also decreases the duration of expiration and increases the burst frequency during gasping. Bilateral vagotomy eliminated these changes. We conclude that the neural substrate mediating the Hering-Breuer reflex is retained in the in situ preparation and that the brain stem circuitry generating the respiratory patterns respond to phasic activation of pulmonary stretch receptors in both eupnea and gasping. These findings support the homology of eupneic phrenic discharge patterns in the reduced in situ preparation and eupnea in vivo and disprove the common supposition that gasping is insensitive to vagal afferent feedback from pulmonary stretch receptor mechanisms.     

Power spectra of inspiratory nerve activity with lung inflations in cats

To investigate the effect of lung inflations on the high-frequency synchrony (70-122 Hz) observed in the inspiratory activity of respiratory motor nerves of decerebrate cats, I applied a step increase in lung inflation pressure at fixed delays into the inspiratory phase and computed power spectra of phrenic neurograms before and during inflation. In 25 decerebrate paralyzed cats the frequency of the high spectral peak was 92.3 +/- 11.1 Hz before and 105.3 +/- 12.1 Hz during the step in inflation pressure, shifting upward by 13.0 +/- 6.0 Hz. For 8 of the 25 cats, the recurrent laryngeal and phrenic neurograms were recorded simultaneously. The high spectral peak was present during inspiration in the recurrent laryngeal power spectra and coherent with the high peak in the phrenic power spectra. In response to lung inflation, the high peak disappeared from the power spectra of the recurrent laryngeal nerve as the inspiratory activity was inhibited; a shift upward in frequency was not detectable. Comparing inspiratory times (TI, based on the phrenic neurograms) for breaths with no lung inflations to those for breaths with lung inflations, I found that lung inflations early in inspiration caused a decrease in TI, lung inflations at intermediates times had no effect on TI, and lung inflations late in inspiration caused an increase in TI. Despite lung inflation decreasing, not affecting, or increasing inspiratory duration and amplitude of the phrenic neurogram, lung inflation always caused a shift upward in the high-frequency peak of the phrenic power density. The fact that lung inflation, a powerful respiratory stimulus, affected the frequency of the high peak in a consistent manner suggests that the high-frequency synchrony is an important and robust feature of the central respiratory pattern generator.     

Interactions between lung stretch and PaCO2 in modulating ventilatory activity in dogs

The effects of changes in airway pressure (Paw) and arterial PCO2 (PaCO2) on ventilatory activity were studied in anesthetized thoracotomized dogs in which both lungs were ventilated separately. Pulmonary artery occlusion on one side and contralateral vagotomy allowed the reflex effects on ventilation of changes in Paw and PaCO2 to be elicited independently of each other. Ventilatory activity was assessed from integrated efferent phrenic activity, analyzed with respect to burst amplitude (Phr), burst frequency (f), and inspiratory TI) and expiratory duration (TE). While Phr increased linearly with PaCO2, it was independent of Paw. Both PaCO2 and Paw affected f in a complex nonadditive way; this response was entirely mediated by effects on TE, TI being unaffected by either stimulus. The analog of ventilation, estimated as Phr x f, increased linearly with PaCO2 and decreased linearly with Paw, but the effects of both stimuli appeared to be additive. It is concluded that the apparently simple effect of Paw and PaCO2 on ventilation results from more complex effects these stimuli exert on its components.     

Phrenic afferents and ventilatory control at increased end-expiratory lung volumes in cats

The role of phrenic afferents in controlling inspiratory duration (TI) at elevated end-expiratory lung volume (EEV) has been studied in pentobarbital-anesthetized, spontaneously breathing cats with intact vagi. Responses to increases in EEV, induced by imposition of an expiratory threshold load (ETL) of 10 cmH2O, were monitored before and after section of cervical dorsal roots C3-C7. The immediate (first-breath) effect of application of ETL was a prolongation of both TI and expiratory duration (TE). After 10 min of breathing against the ETL, average TI returned to control values but TE remained prolonged. Abolishing feedback from the diaphragm did not affect these responses. When steady-state responses to ETL were compared with those elicited by inhalation of 5-6% CO2 in O2, changes in EEV had, on average, no independent effect on respiratory drive (rate of rise of integrated phrenic activity), although phrenic activity increased greatly in some cats despite little or no change in arterial partial pressure of CO2. These data indicate that diaphragmatic receptors do not contribute to either the immediate (first-breath) or steady-state responses of phrenic motoneurons to increases in EEV in intact cats.     

Influence of lung volume on activities of branches of the recurrent laryngeal nerve

To investigate the influence of inspiratory lung inflation on the respiratory activities of laryngeal motor nerves, vagally intact decerebrate paralyzed cats were ventilated by a servorespirator in accordance with their own phrenic nerve activity. Records were made of the activities of the phrenic nerve, the superior laryngeal nerve (SLN), the recurrent laryngeal nerve (RLN), and the intralaryngeal branches of the RLN serving the thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles. Neural activities were assessed in the steady state at different end-tidal O2 and CO2 concentrations. Transient responses to withholding inspiratory lung inflation and to preventing expiratory lung emptying were also studied. Hypercapnia and hypoxia increased the inspiratory activities of the phrenic nerve, SLN, RLN, and its PCA branch. TA inspiratory activity was not changed. Expiratory activities of RLN, PCA, and TA were all increased in hypoxia. When lung inflation was withheld, neural inspiratory duration and the inspiratory activities of all nerves increased. The subsequent period of neural expiration was marked by an exaggerated burst of activity by the TA branch of the RLN. TA expiratory activity was also sharply increased after inspiratory efforts that were reflexly delayed by the prevention of lung emptying. TA activity in expiration was enhanced after vagotomy and was usually more prominent than when lung inflation was withheld before vagal section. The results demonstrate the importance and complexity of the influence of vagal afferents on laryngeal motor activity.     

Effects of hypercapnia on Breuer-Hering threshold for inspiratory termination

The effects of CO2 concentration on the timing of inspiratory duration (TI) and expiratory duration (TE) and the responses to lung inflation were studied in decerebrate paralyzed cats. With lung volume held at functional residual capacity during the breath cycle, hypercapnia (fractional concentration of inspired CO2 = 0.04) caused variable changes in TI and significant increases in TE. To obtain the Breuer-Hering threshold relationship [tidal volume (VT) vs. TI] and the timing relationship between TE and the preceding TI (TE vs. TI), ramp inflations of various sizes were used to terminate inspiration at different times in the breath cycle. Hypercapnia caused the VT vs. TI curves to shift in an upward direction so that at higher lung volumes TI was lengthened. Also, the slope of the TE vs. TI relationship was increased. The results suggest that hypercapnia diminished the sensitivity of the Breuer-Hering reflex to the lung volume, thus allowing volume to increase with little effect on TI. In addition, TE appears to become more sensitive to changes in the preceding TI. A model is presented which provides a possible neural mechanism for these responses.     

Ventilatory response to fatiguing and nonfatiguing resistive loads in awake sheep

To study the changes in ventilation induced by inspiratory flow-resistive (IFR) loads, we applied moderate and severe IFR loads in chronically instrumented and awake sheep. We measured inspired minute ventilation (VI), ventilatory pattern [inspiratory time (TI), expiratory time (TE), respiratory cycle time (TT), tidal volume (VT), mean inspiratory flow (VT/TI), and respiratory duty cycle (TI/TT)], transdiaphragmatic pressure (Pdi), functional residual capacity (FRC), blood gas tensions, and recorded diaphragmatic electromyogram. With both moderate and severe loads, Pdi, TI, and TI/TT increased, TE, TT, VT, VT/TI, and VI decreased, and hypercapnia ensued. FRC did not change significantly with moderate loads but decreased by 30-40% with severe loads. With severe loads, arterial PCO2 (PaCO2) stabilized at approximately 60 Torr within 10-15 min and rose further to levels exceeding 80 Torr when Pdi dropped. This was associated with a lengthening in TE and a decrease in breathing frequency, VI, and TI/TT. We conclude that 1) timing and volume responses to IFR loads are not sufficient to prevent alveolar hypoventilation, 2) with severe loads the considerable increase in Pdi, TI/TT, and PaCO2 may reduce respiratory muscle endurance, and 3) the changes in ventilation associated with neuromuscular fatigue occur after the drop in Pdi. We believe that these ventilatory changes are dictated by the mechanical capability of the respiratory muscles or induced by a decrease in central neural output to these muscles or both.     

Control of respiratory pattern in conscious dog: effects of heat and CO2

We measured tidal volume (VT) and inspiratory (TI) and expiratory (TE) durations in five conscious tracheostomized dogs breathing air or 5% CO2 in air either at normal (20 degrees C) or elevated (30 degrees C) ambient temperatures. Respiratory frequency ranged between 16 and 333/min due to changes in both TI and TE. During panting TI exceeded TE. During air inhalation instantaneous ventilation (V) spontaneously ranged from 100 to 1,600 ml . kg-1 . min-1. Hypercapnia, heat stress, or both, increased this range of V by increasing maximum V, primarily due to increases in mean inspiratory flow. Under these conditions, changes in TI accounted for more of the spontaneous changes in breath duration. During inhalation of air and 5% CO2, a positive correlation between VT and TI was obtained for TI between 0.13 and 1.05 s; above 1.05 s VT decreased. Heat stress increased VT at a given TI. We suggest that either the decay rate or position of the inspiratory off-switch threshold curve (Clark and von Euler, J. Physiol. London 222: 267, 1972) varies in conscious dogs. Shifts in either the reset (onset) value or decay rate of the curve yield a positive correlation between VT and TI. This modification to the Clark-von Euler model implies that the primary effect of anesthesia on respiratory control is fixation of the inspiratory off-switch threshold curve.     

Control of breathing at elevated lung volumes in anesthetized cats

We monitored the steady-state ventilatory responses of anesthetized cats to increases in lung volume produced by expiratory threshold loads (ETL) to study the roles of peripheral and central neural mechanisms in controlling respiration at elevated lung volumes. Application of an ETL of 5 cmH2O produced a significant decrease in respiratory frequency (-18%) but no change in minute ventilation (VE) due to a significant increase in tidal volume (VT) (19.3%). The drop in frequency was due solely to an increase in expiratory duration. ETL of 10 cmH2O significantly reduced VE (-17.5%) for the same reason. VT was maintained or increased at elevated lung volumes due to both an increase in the rate of rise of phrenic activity and a maintenance of inspiratory duration (TI) despite increases in both chemical drive and pulmonary stretch receptor (PSR) activity. No PSR adapted completely to the maintained change in lung volume. The sensitivity of the inspiratory off-switch mechanism to increases in lung volume, given by the reciprocal of the VT-TI relationship, decreased significantly during breathing on ETL. The results are consistent with the hypothesis that central habituation, not just peripheral adaptation of PSR, determines breathing pattern at elevated lung volumes.     

On the relation between expiratory duration and subsequent inspiratory duration

To characterize respiratory interphase relationships in dogs, inspiratory duration (TI) or expiratory duration (TE) was systematically altered by electrical activation of vagal afferents, and the effect on subsequent TE or TI values was measured from the phrenic discharge. A linear TI-subsequent TE relationship was found. Following a vagally mediated prolongation of TE, 1) TI was prolonged, and the TE-subsequent TI relationship was curvilinear, 2) the threshold for inspiratory termination by phasic vagal inputs was increased, 3) the amplitude of the time course of the phrenic discharge was reduced so that the peak discharge reached the same level at inspiratory termination independent of TI, 4) the effect on TI prolongation persisted for several breaths whereas the effect was minimal on subsequent TE values, and 5) for tonic inputs the direct shortening of TI was nearly offset by the indirect lengthening of TI. These studies suggest the existence of slow central mechanisms that provide adaptation to elevated levels of vagal input in the control of TI. These mechanisms may also be responsible for the interphase timing relationships.     

Differential timing of respiratory muscles in response to chemical stimuli in awake dogs

We assessed changes in respiratory muscle timing in response to hyperpnea and shortened inspiratory and expiratory times caused by chemoreceptor stimuli in six awake dogs. Durations of postinspiratory inspiratory activity of costal and crural diaphragm (PIIA), the delay in diaphragm electromyogram (EMG) after the initiation of inspiratory airflow, postexpiratory expiratory activity of the transversus abdominis (PEEA), and the delay of abdominal expiratory muscle activity after the initiation of expiratory airflow were measured. In control, four out of six dogs showed PIIA [8-10% of expiratory time (TE)]; all showed delay of diaphragm [19% of inspiratory time (TI)], delay of abdominal muscle activation (21% of TE), and PEEA (24% of TI). Hypercapnia decreased PIIA (4-9% of TE), maintained diaphragm delay at near control values (23% of TI), increased PEEA (36% of TI), eliminated delay of abdominal muscle activation (4% of TE), and decreased end-expiratory lung volume (EELV). Hypocapnic hypoxia increased PIIA (24-25% of TE), eliminated diaphragm delay (3% of TI), eliminated PEEA (3% of TI), reduced delay of abdominal muscle activation (14% of TE), and increased EELV. Most of these effects of hypoxic hypocapnia vs. hypercapnia on the within-breath EMG timing parameters corresponded to differences in the magnitude of expiratory muscle activation. These changes exerted significant influences on flow rates and EELV.     

Postnatal maturation of ventilation and breathing pattern in kittens: influence of sleep

Ventilation and breathing pattern were studied in kittens at 1, 2, 3, 4, and 8 wk of life during quiet wakefulness (W), quiet sleep (QS), and active sleep (AS) with the barometric method. Tidal volume (VT), respiratory frequency (f), ventilation (VE), inspiratory time (TI), expiratory time (TE), mean inspiratory flow (VT/TI), and respiratory "duty cycle" (TI/TT) were measured. VT, VE, TI, TE, and VT/TI increased; f decreased and TI/TT remained constant during postnatal development in wakefulness and in both sleep states. No significant difference was observed between AS and QS for all the ventilatory parameters except TI/TT, which was greater in QS than in AS at 2 wk. VE was larger in W than in both AS and QS at all ages. This was mainly due to a greater f, TI/TT remaining constant. VT/TI, which represents an index of the central inspiratory activity, was larger in W than in sleep, VT not being significantly different whatever the stage of consciousness. The results of this study show that in the kitten 1) unlike in the adult cat, ventilation and breathing pattern are similar in QS and in AS; 2) in sleep, the central inspiratory drive appears to be independent of the type of sleep; and 3) in wakefulness, the increase of the central inspiratory activity could be related to important excitatory inputs.     

Expiratory flow pattern and respiratory mechanics

During resting breathing, expiration is characterized by the narrowing of the vocal folds which, by increasing the expiratory resistance, raises mean lung volume and airway pressure. This is even more pronounced in the neonatal period, during which expirations with short complete airway closure are commonly occurring. We asked to which extent differences in expiratory flow pattern may modify the inspiratory impedance of the respiratory system. To this aim, newborn puppies, piglets, and adult rats were anesthetized, paralyzed, and ventilated with different expiratory patterns, (a) no expiratory load, (b) expiratory resistive load, and (c) end-inspiratory pause. The stroke volume of the ventilator and inspiratory and expiratory times were maintained constant, and the loads were adjusted in such a way that inflation always started from the resting volume of the respiratory system. After 1 min of each ventilatory pattern, mean inspiratory impedance and compliance of lung and respiratory system were measured. The values were unchanged or minimally altered by changing the type of ventilation. We conclude that the expiratory laryngeal loading is not primarily aimed to decrease the work of breathing. It is conceivable that the expiratory pattern is oriented to increase and control mean airway pressure in the regulation of pulmonary fluid reabsorption, distribution of ventilation, and diffusion of gases.     

Respiratory responses in reversible diaphragm paralysis

The effects of diaphragm paralysis on respiratory activity were assessed in 13 anesthetized, spontaneously breathing dogs studied in the supine position. Transient diaphragmatic paralysis was induced by bilateral phrenic nerve cooling. Respiratory activity was assessed from measurements of ventilation and from the moving time averages of electrical activity recorded from the intercostal muscles and the central end of the fifth cervical root of the phrenic nerve. The degree of diaphragm paralysis was evaluated from changes in transdiaphragmatic pressure and reflected in rib cage and abdominal displacements. Animals were studied both before and after vagotomy breathing O2, 3.5% CO2 in O2, or 7% CO2 in O2. In dogs with intact vagi, both peak and rate of rise of phrenic and inspiratory intercostal electrical activity increased progressively as transdiaphragmatic pressure fell. Tidal volume decreased and breathing frequency increased as a result of a shortening in expiratory time. Inspiratory time and ventilation were unchanged by diaphragm paralysis. These findings were the same whether O2 or CO2 in O2 was breathed. After vagotomy, no significant change in phrenic or inspiratory intercostal activity occurred with diaphragm paralysis in spite of increased arterial CO2 partial pressure. Ventilation and tidal volume decreased significantly, and respiratory timing was unchanged. These results suggest that mechanisms mediated by the vagus nerves account for the compensatory increase in respiratory electrical activity during transient diaphragm paralysis. That inspiratory time is unchanged by diaphragm paralysis whereas the rate or rise of phrenic nerve activity increases suggest that reflexes other than the Hering-Breuer reflex contribute to the increased respiratory response.     

Bradykinin stimulates respiratory drive by activating pulmonary sympathetic afferents in the rabbit.

We recently identified a vagally mediated excitatory lung reflex by injecting hypertonic saline into the lung parenchyma (Yu J, Zhang JF, and Fletcher EC. J Appl Physiol 85: 1485-1492, 1998). This reflex increased amplitude and burst rate of phrenic (inspiratory) nerve activity and suppressed external oblique abdominal (expiratory) muscle activity. In the present study, we tested the hypothesis that bradykinin may activate extravagal pathways to stimulate breathing by assessing its reflex effects on respiratory drive. Bradykinin (1 microg/kg in 0.1 ml) was injected into the lung parenchyma of anesthetized, open-chest and artificially ventilated rabbits. In most cases, bradykinin increased phrenic amplitude, phrenic burst rate, and expiratory muscle activity. However, a variety of breathing patterns resulted, ranging from hyperpnea and tachypnea to rapid shallow breathing and apnea. Bradykinin acts like hypertonic saline in producing hyperpnea and tachypnea, yet the two agents clearly differ. Bradykinin produced a higher ratio of phrenic amplitude to inspiratory time and had longer latency than hypertonic saline. Although attenuated, bradykinin-induced respiratory responses persisted after vagotomy. We conclude that bradykinin activates multiple afferent pathways in the lung; portions of its respiratory reflexes are extravagal and arise from sympathetic afferents.     

Excitatory lung reflex may stress inspiratory muscle by suppressing expiratory muscle activity.

Recently, a vagally mediated excitatory lung reflex (ELR) causing neural hyperpnea and tachypnea was identified. Because ventilation is regulated through both inspiratory and expiratory processes, we investigated the effects of the ELR on these two processes simultaneously. In anesthetized, open-chest, and artificially ventilated rabbits, we recorded phrenic nerve activity and abdominal muscle activity to assess the breathing pattern when the ELR was evoked by directly injecting hypertonic saline (8.1%, 0.1 ml) into lung parenchyma. Activation of the ELR stimulated inspiratory activity, which was exhibited by increasing amplitude, burst rate, and duty cycle of the phrenic activity (by 22 +/- 4, 33 +/- 9, and 57 +/- 11%, respectively; n = 13; P < 0.001), but suppressed expiratory muscle activity. The expiratory muscle became silent in most cases. On average, the amplitude of expiratory muscle activity decreased by 88 +/- 5% (P < 0.002). The suppression reached the peak at 6.9 +/- 1 s and lasted for 200 s (median). Injection of H(2)O(2) into the lung parenchyma produced similar responses. By suppressing expiration, the ELR produces a shift in the workload from expiratory muscle to inspiratory muscle. Therefore, we conclude that the ELR may contribute to inspiratory muscle fatigue, not only by directly increasing the inspiratory activity but also by suppressing expiratory activity.     

Effects of acute hyperbaric oxygenation on respiratory control in cats

We studied ventilatory responsiveness to hypoxia and hypercapnia in anesthetized cats before and after exposure to 5 atmospheres absolute O2 for 90-135 min. The acute hyperbaric oxygenation (HBO) was terminated at the onset of slow labored breathing. Tracheal airflow, inspiratory (TI) and expiratory (TE) times, inspiratory tidal volume (VT), end-tidal PO2 and PCO2, and arterial blood pressure were recorded simultaneously before and after HBO. Steady-state ventilation (VI at three arterial PO2 (PaO2) levels of approximately 99, 67, and 47 Torr at a maintained arterial PCO2 (PaCO2, 28 Torr) was measured for the hypoxic response. Ventilation at three steady-state PaCO2 levels of approximately 27, 36, and 46 Torr during hyperoxia (PaO2 450 Torr) gave a hypercapnic response. Both chemical stimuli significantly stimulated VT, breathing frequency, and VI before and after HBO. VT, TI, and TE at a given stimulus were significantly greater after HBO without a significant change in VT/TI. The breathing pattern, however, was abnormal after HBO, often showing inspiratory apneusis. Bilateral vagotomy diminished apneusis and further prolonged TI and TE and increased VT. Thus a part of the respiratory effects of HBO is due to pulmonary mechanoreflex changes.     

Effect of pulmonary arterial PCO2 on breathing pattern

We studied breathing patterns and tidal volume (VT)-inspiratory time (TI) relationships at three steady-state levels of pulmonary arterial PCO2 (PpCO2) in 10 anesthetized dogs. To accomplish this we isolated and then separately pump perfused the pulmonary and systemic circulations, which allowed us to control blood gases in each circuit independently. To ventilate the lungs at a rate and depth determined by central drive, we used an electronically controlled positive-pressure ventilator driven by inspiratory phrenic neural activity. Expiratory time (TE) varied inversely with PpCO2 over the range of PpCO2 from approximately 20 to 80 Torr. VT and TI increased with rising PpCO2 over the range from approximately 20 to 45 Torr but did not change further as PpCO2 was raised above the middle level of approximately 45 Torr. Thus minute ventilation increased as a function of TE and VT as PpCO2 was increased over the lower range and increased solely as a function of TE as PpCO2 was increased over the upper range. The VT-TI relationship shifted leftward on the time axis as PpCO2 was lowered below the middle level but did not shift in the opposite direction as PpCO2 was raised above the middle level. In addition to its effect on breathing pattern, we found that pulmonary hypocapnia depressed inspiratory drive.