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Rhythmic contractions of the detrusor muscle, induced by gradual filling of the urinary bladder in decerebrate or anesthetized cats, are accompanied by decreased inspiratory activity in motor nerves to respiratory muscles, particularly those of the upper airway. We have examined the influence of hypercapnia and hypocapnia on these contractions and the accompanying activities of the phrenic and hypoglossal nerves in decerebrate, vagotomized, paralyzed and ventilated cats, some of which had denervated carotid chemoreceptors. Hypercapnia slowed, and then reversibly abolished bladder contractions in most animals, regardless of the state of the carotid chemoreceptors. Bladder contractions were well maintained in progressive hypocapnia, even at end-tidal CO(2) levels below the 'apneic' thresholds of the hypoglossal and phrenic activities. The reductions of the nerve activities in response to bladder contractions were not significantly altered by hypercapnia or hypocapnia. The abolition of bladder contractions by hypercapnia is unlikely to reflect a direct effect of CO(2) or H+ ion on the contractile mechanism of the detrusor muscle, but may be based on inhibition of stretch receptors in the bladder wall and/or an effect of CO(2) or H+ in or near the micturition centers in the brain stem.

In decerebrate or anesthetized cats with moderately distended urinary bladders, spontaneous bladder contractions (SBCs) have been shown to decrease phrenic and hypoglossal nerve activities. To determine the involvement of both the pontine micturition center (PMC) and the pneumotaxic center in the respiratory response to SBCs, we recorded phrenic and hypoglossal nerve activities in decerebrate, paralyzed, vagotomized, artificially ventilated cats. Electrical stimulation of the PMC in cats with subthreshold bladder volumes below the threshold for SBCs elicited both increases in intravesical pressure (IVP) and attenuation of respiratory motor nerve activities. Respiration was not altered after PMC lesions, which abolished SBCs, contractions in response to PMC stimulation, and respiratory inhibition due to passive bladder distension. Electrical stimulation of the pneumotaxic center altered respiratory motor nerve activities and increased IVP in cats with subthreshold bladder volumes. Pneumotaxic center lesions caused apneusis, but did not abolish the SBCs, which continued to attenuate the apneustic respiratory motor nerve activity. These results indicate that the PMC is an important component of the reflex pathway from urinary bladder distension to respiratory inhibition, whereas the pneumotaxic center does not appear to be an essential part of this pathway.

In decerebrate, vagotomized cats, introduction of CO2 into the isolated laryngeal airway while systemic PCO2 is held constant evokes dose-related reflex changes in ventilatory activity. Because systemic hypoxia is known to exaggerate ventilatory responses to other types of laryngeal chemostimulation in neonates, we have compared the responses of phrenic and hypoglossal nerve activities to ventilation of the larynx with 10% CO2 during systemic hyperoxia (FIO2 = 1.00) to those during hypoxia (FIO2 = 0.12). Compared with the hyperoxic baseline condition, hypoxia stimulated phrenic activity but attenuated the reduction in phrenic activity evoked by intralaryngeal CO2. Hypoglossal activity was increased by intralaryngeal CO2 and this response appeared to be reduced by hypoxia, but neither of these findings was statistically significant. The response of phrenic activity to intralaryngeal CO2 during systemic hypercapnia was similar to that during hypoxia. The increase of phrenic activity in response to hypoxia was prevented by carotid body resection. Similarly, the hypoxic attenuation of the phrenic response to intralaryngeal CO2 appeared to be absent after carotid body resection, although this finding was not established statistically. These results differ from previous reports of exaggerated laryngeal chemoreflex responses during hypoxia. The difference may reflect differences in the receptors and synaptic mechanisms of the reflexes, the severity and time course of hypoxia or the presence or depth of general anesthesia or sleep.

1. We investigated the responses of phrenic and hypoglossal nerve activities to the addition of 3, 5 and 10% CO2 to a constant flow of warm, humidified air through the isolated upper airway in decerebrate, paralysed, artificially ventilated cats. 2. In bilaterally vagotomized animals, intralaryngeal CO2 caused a dose-related decrease in peak integrated phrenic activity. This response became attenuated with time, but was still discernible after 3 min of continuous intralaryngeal CO2. In the same experiments, intralaryngeal CO2 caused a gradual increase in peak integrated hypoglossal nerve activity. 3. Intermittent pulsing of intralaryngeal CO2 during neural inspiration or expiration resulted in similar, but smaller decreases in the phrenic activity of some animals. Hypoglossal activity was not influenced appreciably by this procedure. 4. Systemic hypercapnia attenuated the phrenic responses to intralaryngeal CO2. The hypoglossal responses were greatly reduced or abolished. 5. In vagally intact cats, ventilated by a servo-respirator in accordance with phrenic nerve activity, intralaryngeal CO2 resulted in only a trace of reduction in phrenic discharge. After bilateral vagotomy, the same animals showed typical responses, as described above. 6. All responses to intralaryngeal CO2 were abolished after bilateral section of the superior laryngeal nerves (SLNs). 7. We conclude that intralaryngeal CO2 acts by way of receptors with afferents in the SLNs to decrease phrenic and increase hypoglossal nerve activities. The responses are not importantly gated during neural inspiration or expiration. The responses to intralaryngeal CO2 are most clearly demonstrable after bilateral vagotomy, suggesting that vagal mechanisms serve to stabilize respiratory motor neural activity in intact animals.

Tegu lizards decrease ventilatory frequency (f) when constant CO2, as low as 0.4%, is delivered to the nasal cavities. In contrast, CO2, as high as 6%, pulsed into the nasal cavities during the expiratory phase of the breathing cycle does not alter f. The purpose of the present study was to investigate further the effect of nasal CO2 pattern on f in tegu lizards. Specifically, we tested: (1) whether f was affected by CO2 delivered to the nasal cavities during the inspiratory phase of the breathing cycle, and (2) whether pulsed decreases in nasal CO2 from 4% to 2% and from 4% to 0% would remove the f inhibition caused by constant nasal CO2. Ventilation was measured using a pneumotachograph and pressure transducer in-line with an endotracheal T-tube inserted through the glottis. CO2 was delivered to the nasal cavities through small tubes inserted into the external nares. Ventilatory frequency was not significantly altered when 4% CO2 was pulsed into the nasal cavities during inspiration. Dropping the CO2 in the nasal cavities from 4% to 0% at either 15 cycles/min (0.25 Hz) or for one cycle stimulated breathing. There was no significant difference between the f response to a drop in CO2 from 4% to 0% and that to a drop in CO2 from 4% to 2%. The failure to link the phasic CO2 ventilatory response to a phase in the respiratory cycle indicates that the nasal CO2 receptors do not participate in the breath-by-breath regulation of breathing in these lizards. The observation that small decreases in nasal CO2 abolished the f inhibition caused by constant nasal CO2 provides further evidence for the ability of the nasal CO2 receptors to distinguish between pulsed and constant CO2.

Garter snakes were used to study the effects of venous CO2 loading using the skin as an exchanger. The gaseous environment surrounding the snake's body was isolated by placing the body in a plethysmograph with the head out. While the animal breathed room air, the carbon dioxide concentration within the plethysmograph was varied between 0 and 80%. Room air was drawn through a funnel placed over the snake's head, thus collecting the exhaled gases, and this gas was analyzed by O2 and CO2 analyzers. The descending aorta was cannulated to measure blood gases. Expired CO2 flow rose linearly with increasing cutaneous CO2. Ventilation increased 3.5-fold at 80% cutaneous CO2 compared with no cutaneous CO2 load. Neither the mean CO2 concentration in exhaled air nor arterial PCO2 changed when the snake was exposed to high levels of CO2 at the skin. Thus ventilation increased in proportion to the CO2 load, and was not driven by arterial hypercapnia. Bilateral vagotomy eliminated arterial CO2 homeostasis during cutaneous CO2 loading, and ventilation increased with increasing arterial PCO2. Therefore, these snakes respond to extra-arterial elevations in CO2 or to a changing CO2 signal. Furthermore, receptors responsible for the increase in ventilation when venous CO2 is elevated have neurons in the vagus nerves.

Our purpose was to examine the influence of phasic lung volume feedback on the activities of motor nerves innervating the diaphragm and transversus abdominis muscles during hypercapnia and hypoxia. We studied seventeen decerebrate cats that were paralyzed and ventilated with a servo-respirator controlled by the integrated phrenic neurogram. The effects of phasic lung volume feedback were assessed by withholding pulmonary inflation during the central inspiratory period. Withholding lung inflation for a single respiratory cycle under hyperoxic, normocapnic conditions consistently prolonged the durations of the inspiratory and expiratory periods, and caused marked increases in the peak electrical activities of both phrenic and abdominal nerves. Hyperoxic hypercapnia (PaCO2 50-80 mmHg) and isocapnic hypoxia (PaO2 60-35 mmHg) increased peak phrenic and abdominal neural activities, and withholding pulmonary inflation under these conditions caused even greater augmentations of inspiratory and expiratory motor output. The augmentation of expiratory activity by withholding lung inflation was proportionately greater than the concomitant prolongation of the central expiratory period. All responses to non-inflation maneuvers were abolished following bilateral cervical vagotomy. The results indicate that vagally mediated volume feedback during inspiration can attenuate the output of abdominal motoneurons in the subsequent expiratory period. Moreover, hypoxia, which attenuates abdominal motor activity in vagotomized animals, enhances this activity when the vagi are intact.

Single-fiber phrenic nerve action potentials were recorded together with activity of contralateral whole phrenic nerve rootlets during eupnea and gasping in decerebrate, cerebellectomized, vagotomized, paralyzed, and ventilated cats. Gasping was reversibly produced by cooling a fork thermode positioned through the pontomedullary junction. In eupnea, phrenic motoneurons were distributed into "early" and "late" populations relative to their onset of activity during inspiration. During gasping, however, both fiber types typically commenced activity at the beginning of the phrenic nerve burst. Moreover, late fibers, but not early units, exhibited an augmentation of discharge frequency with the onset of gasping. The concentration of activity of all phrenic motoneurons at the beginning of inspiration and the increase in late-unit discharge frequency account for the faster rise of the gasp as compared with the eupneic breath. It is concluded that the pattern of phrenic nerve activation during gasping differs fundamentally from that during eupnea. These results support the concept that mechanisms underlying the neurogenesis of gasping and eupnea may not be identical.

We have studied the pattern of breathing before, during and after augmented breaths in spontaneously breathing, anesthetized cats with the larynx both in and out of the breathing circuit. Following augmented breaths we consistently observed increases in end-expiratory lung volume (EEV), end-expiratory transpulmonary pressure, dynamic lung compliance and respiratory frequency. These changes were of similar magnitude whether the larynx was in or out of circiut and were uninfluenced by section of the superior laryngeal nerves. Laryngeal resistance, measured under constant flow conditions with the larynx removed from the breathing circuit, showed an exaggerated inspiratory decrease during augmented breaths. Passive lung inflations, performed so as to mimic the pattern of augmented breaths, increased dynamic lung compliance but did not elicit changes in EEV or respiratory frequency. The results indicate that the increase in EEV cannot be attributed to increased lung compliance but results from a change in end-expiratory respiratory muscle tone. This change, and the change in respiratory frequency appear to be part of a reflexly evoked central response that includes the augmented breath itself. The larynx participates in the augmented breath, but its mechanical importance is small.

Our purpose was to determine whether the intensity of abdominal expiratory nerve discharge is conditioned by the intensity of the preceding inspiratory phrenic discharge, independent of mechanical and chemical afferent influences. In decerebrate, paralyzed, vagotomized cats with bilateral pneumothoraxes, we recorded phrenic and abdominal (cranial iliohypogastric nerve, L1) nerve activities at hyperoxic normocapnia. We reduced the duration and intensity (i.e., integrated peak height) of phrenic nerve discharge for single cycles by stimulating the cut central end of the superior laryngeal nerve (SLN) during the central inspiratory phase (75 microA, 20-50 Hz, 0.2-ms pulse). Premature termination of inspiration consistently reduced expiratory duration (TE) and abdominal expiratory nerve activity (area of integrated neurogram), but the average reduction in TE was much less than the reduction in abdominal nerve activity (14 vs. 51%). Stimulation of the cut central end of the vagus nerve yielded similar results, as did spontaneous premature terminations of inspiration, which we observed in one cat. SLN stimulation during hyperoxic hypercapnia resulted in more variable responses, and higher stimulation frequencies were usually required to abort inspiration. SLN (or vagal) stimulation during expiration consistently increased abdominal expiratory nerve activity. We speculate that this facilitatory response is gated during inspiration, thereby allowing the inspiratory conditioning effect on the subsequent expiration to be expressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Respiratory vocal cord movements were analyzed in healthy human subjects during air breathing and in isocapnic hypoxia and hypercapnia. In the majority of experiments, expiratory glottic narrowing was substantially greater during hypoxia than during hypercapnia. Because ventilations were carefully matched under these two conditions, it is concluded that hypoxic stimulation of peripheral chemoreceptors favors expiratory glottic narrowing and leads to a relatively high laryngeal airflow resistance. In contrast, hypercapnia is accompanied by low expiratory laryngeal resistance. Similar rates of expiratory airflow with these two stimuli must be achieved by different balances of the factors that determine this flow.

Ventilation and lung volume were measured in unanesthetized garter snakes using a headout body plethysmograph. The breathing cycle consisted of expiration, inspiration and a prolonged post-inspiratory breath-holding period, which lasted until the onset of the next expiration. Hypoxia induced increases in VT and in the volume at which the breath was held between cycles. Hypercapnia usually elicited hyperpnea after an initial, transient inhibition of breathing movements, but was accompanied by little or no increase in breath-holding lung volume. Snakes with T-tube tracheostomies failed to maintain the normal positive intrapulmonary pressure during the breath-holding period and failed to increase breath-holding lung volume in hypoxia, despite increased inspiratory excursions. These studies demonstrate a pronounced increase in lung volume during hypoxia and indicate that this response requires an intact upper airway. These findings in a reptile may be related in evolutionary terms to the increase in lung volume and post-inspiratory laryngeal narrowing that occur in mammals during hypoxia.

Our purpose was to examine the influence of steady-state changes in chemical stimuli, as well as discrete peripheral chemoreceptor stimulation, on abdominal expiratory motor activity. In decerebrate, paralyzed, vagotomized, and ventilated cats that had bilateral pneumothoraces, we recorded efferent activity from a phrenic nerve and from an abdominal nerve (cranial iliohypogastric nerve, L1). All cats showed phasic expiratory abdominal nerve discharge at normocapnia [end-tidal PCO2 38 +/- 2 Torr], but small doses (2-6 mg/kg) of pentobarbital sodium markedly depressed this activity. Hyperoxic hypercapnia consistently enhanced abdominal expiratory activity and shortened the burst duration. Isocapnic hypoxia caused inhibition of abdominal nerve discharge in 11 of 13 cats. Carotid sinus nerve denervation (3 cats) exacerbated the hypoxic depression of abdominal nerve activity and depressed phrenic motor output. Stimulation of peripheral chemoreceptors with NaCN increased abdominal nerve discharge in 7 of 10 cats, although 2 cats exhibited marked inhibition. Four cats with intact neuraxis, but anesthetized with ketamine, yielded qualitatively similar results. We conclude that when cats are subjected to steady-state chemical stimuli in isolation (no interference from proprioceptive inputs), hypercapnia potentiates, but hypoxia attenuates, abdominal expiratory nerve activity. Mechanisms to explain the selective inhibition of expiratory motor activity by hypoxia are proposed, and physiological implications are discussed.

Responses of expiratory duration (TE) and laryngeal aperture to small flow resistance loads (2 and 5 cm H2O/LPS) applied to single expirations were measured using repeated applications in four subjects during quiet breathing. All subjects significantly prolonged TE in response to the higher load and 3 of the 4 showed that same response to the lower load, which was not perceived by these subjects. These same 3 subjects showed a narrowed laryngeal aperture in response to loading such that their expiratory impedance must have been greater than the increase provided by the load alone. The effect of such a loading response was to slow the expiratory volume decay so that a small but significant increase in the halftime for volume decay was observed. The prolongation of TE seen with loading could be due to the alteration of volume-related feedback consequent to the increased expiratory impedance. This may serve a role in regulation of expiratory muscle function.

A consequence of the adaptation of pulmonary stretch receptors is that their pattern of discharge depends on both lung volume and its rate of change. For adaptation dependent, flow related information to modify the breathing pattern by a feedback process, appreciable receptor adaptation must take place during a single respiratory cycle. Moreover, for flow related information to have the same significance in all animals, the time course of stretch receptor adaptation would have to vary among species, being more rapid in small animals, with high respiratory frequencies. We recorded single fiber action potentials from 84 pulmonary stretch receptors in six species of mammals, ranging from hamster to dog. The response of the receptors to maintained transpulmonary pressures was similar in the different species,as was the time course of receptor adptation following sudden lung inflations to 5 and 10 cm H2O. These findings show that the behavior of pulmonary stretch receptors is similar in animals with widely differing respiratory frequencies, and that the significance of receptor adaptation for regulation of the breathing pattern must vary interspecifically.

This study was undertaken to assess the role of intrapulmonary chemoreceptors in the control of breathing in reptiles. Garter snakes were tracheostomized to remove the influence of upper airway receptors. After recovery from anesthesia, the animals were unidirectionally ventilated or allowed to ventilate normally, but without glottal control of the breath-hold. Breathing movements were recorded by means of a pneumotachograph. When a bidirectionally breathing snake was presented with CO2 at the tracheal tube, inspiratory duration and volume decreased. When CO2 was removed from the inspired air between breaths, inspiratory duration and volume increased. Removing CO2 from the airstream of a unidirectionally ventilated snake during a breath-hold produced apnea, but removing CO2 at the beginning of inspiration caused the duration and volume of the inspiration to increase. This reflex appears to represent a positive feedback mechanism for enhancing inspiration once a breath has been initiated.

In decerebrate, vagotomized, paralyzed, and ventilated cats, phrenic and respiratory-related hypoglossal discharges were evident at normocapnic normoxia or hyperoxia. Both increased progressively in hypercapnia or hypoxia. With increasing drive, onset of inspiratory hypoglossal activity began earlier relative to phrenic onset; an early expiratory hypoglossal burst was also observed. Following subanesthetic doses of chloralose, halothane, ketamine, or pentobarbital, hypoglossal activity was depressed much more than phrenic discharge. In moderate hypercapnia or hypoxia, phrenic activity increased more than hypoglossal, whereas, at high drive, the latter rose more sharply in some cats. Electromyograms of the diaphragm and genioglossus were recorded in intact awake cats to determine if their responses and those of decerebrates are comparable. Respiratory-related genioglossal discharge was evident in normocapnia. We conclude that anesthesia suppresses hypoglossal motor activities much more than those of the bulbospinal-phrenic system. Data for decerebrate cats and unanesthetized cats or humans provide no evidence of a differential distribution of chemoreceptor afferents on hypoglossal and bulbospinal-phrenic neurons, as suggested by results in anesthetized animals.

Using a fiberoptic laryngoscope and video equipment, we studied the respiratory movements of the vocal cords during sustained hyperventilation in 4 normal human subjects. The expiratory narrowing of the glottic airway that occurs in quiet breathing was attenuated during hyperventilation in 7 of 8 experiments, and the pattern of vocal cord movements throughout the breathing cycle closely resembled the patterns previously found in exercise and hypercapnia. These responses were similar during normocapnic and hypocapnic hyperventilation. The similarity of laryngeal movements in voluntary and involuntary hyperpneic states suggests that common brain stem mechanisms may be entrained by both 'behavioral' and 'automatic' ventilatory control systems.

Our purpose was to characterize activities of phrenic motoneurons during apneusis. In decerebrate, cerebellectomized, vagotomized, paralyzed and ventilated cats, we recorded activities of phrenic nerve and single phrenic fibers during eupnea and apneusis. Reversible apneusis was obtained by cooling the rostral pons with a fork thermode. Phrenic motoneurons were defined as 'early' or 'late' during eupnea. Early units commenced activity before or during the first 20% of neural inspiration. The onset of discharge of late units extended throughout the rest of inspiration. In apneusis, some late units ceased activity entirely; others commenced activity at the end of the rising phase of phrenic activity or during the apneustic plateau. Early units commenced activities at the same time as in eupnea and generally maintained the same discharge frequency. Hence, the ramp phase of phrenic discharge in apneusis is generated largely by activities of early motoneurons. Our results imply that the level of bulbospinal activity impinging upon the phrenic nucleus is reduced in apneusis. The integration of efferent activity within the phrenic nucleus is discussed.

The pattern of respiratory movements of the vocal cords in relation to airflow and respiratory system resistance was assessed in healthy human volunteers during quiet breathing. Motion pictures of the vocal cords were obtained through a fiber-optic laryngoscope inserted transnasally under topical anesthesia. A simultaneous estimate of lung volume was obtained using either rib cage and abdominal magnetometer coils or an integrated pneumotachograph signal. The vocal cords separated during inspiration and moved closer together during the expiratory phase of each breath. The extent of these movements varied greatly among the subjects. Total respiratory system resistance, assessed by the forced oscillation technique, was negatively correlated with distance between the vocal cords when measured at isoflow points in inspiration and expiration. Analysis of breath-by-breath variations in expiratory airflow and vocal cord position revealed that decreases in airflow accompanied decreases in the distance between the vocal cords. The results of this study indicate that the human larynx participates in the regulation of respiratory airflow by providing a variable, controlled resistance.

Upper airway obstruction during sleep occurs more commonly in men than in women and has been treated with progestational agents with some success. Alcohol ingestion exacerbates sleep apnea, and recent studies have established that alcohol depresses the respiratory motor activity to upper airway muscles more than that to the diaphragm, a response pattern that favors upper airway obstruction during inspiration. To investigate the possibility that progesterone provides some protection from this action of alcohol, we studied the responses of phrenic and hypoglossal nerve activities to alcohol infusion in decerebrate cats pretreated with medroxyprogesterone acetate (MPA) or with control injections. The results indicate that pretreatment with MPA reduces the alcohol-induced mismatching of hypoglossal and phrenic activities. This action of MPA may contribute to its effectiveness in the treatment of some patients with inspiratory obstruction during sleep.

When lung inflation is temporarily withheld in paralyzed, ventilated cats with intact vagi, the activities of inspiratory motor nerves are greater during the second cycle without inflation than during the first. This response is not easily attributable to increasing drive from chemoreceptors as it is abolished by vagotomy. We examined the hypothesis that the increasing inspiratory activity is the result of decreasing inhibitory feedback from pulmonary stretch receptors (PSRs). Decerebrate, paralyzed cats were ventilated by a servo-respirator in accordance with their own phrenic nerve activity. Afferent activities from individual PSRs were recorded from a few cut fibers of one vagus nerve; the vagi were otherwise intact. When lung inflation was withheld, phrenic and hypoglossal nerve activities and the durations of inspiration and expiration all increased and were significantly greater during the second cycle without inflation than during the first. The frequency of PSR discharge was also greater during the second cycle and thus did not account for the responses recorded from the motor nerves. We conclude that the latter responses probably reflect neural processes within the brain stem, involving a persistent inhibitory influence from lung inflation, which outlasts the inflation itself.

Breath holding to the breaking point was studied at FRC in six healthy subjects in the sitting position. Breath-holding time increased with successive trials within experimental sessions in all subjects. To study the influence of Valsalva and Mueller maneuvers on breath-holding performance, sustained inspiratory or expiratory effort against an occluded mouthpiece was initiated 5 s before the anticipated breaking point, determined in previous trials. The subject tried to maintain a target mouth pressure of +20 or -20 cmH2O, displayed on an oscilloscope, for the remainder of the breath hold. Both types of maneuver consistently prolonged breath-holding time in all subjects. However, a control maneuver, in which the subjects squeezed rubber bulbs with their hands, was equally effective in prolonging breath-holding time. The results demonstrate the important influence of psychological factors on breath-holding performance and emphasize the need for caution in the interpretation of effects of "relieving maneuvers" on breath-holding time.

In decerebrate, paralyzed cats, ventilated by a servo-respirator in accordance with phrenic nerve activity, we examined the influence of lung volume on the activities of the phrenic, hypoglossal and mylohyoid nerves. When lung inflation was briefly withheld, the durations of inspiration (TI) and expiration (TE) and the activities of all three nerves increased. The relative increase in hypoglossal activity greatly exceeded that of phrenic activity and was apparent earlier in the course of inspiration. This hypoglossal response was enhanced by hypercapnia and isocapnic hypoxia. The responses of mylohyoid activity were quite variable: withholding lung inflation augmented inspiratory activity in some cats, but expiratory discharge in others. Sustained increases in end-expiratory lung volume were induced by application of 3-4 cm H2O of positive end-expiratory pressure (PEEP). Steady-state PEEP did not influence nerve activities or the breathing pattern. Bilateral vagotomy increased TI, TE, and the activities of all three nerves. No response to withoholding lung inflation could be discerned after vagal section. The results provide further definition of the influence of vagally mediated, lung volume dependent reflexes on the control of upper airway muscles. These reflexes are well suited to relieve or prevent upper airway obstruction.

To distinguish experimentally between motor nerve activity destined for vocal cord abductor muscles and that bound for muscles that adduct the cords, we recorded efferent activities of intralaryngeal branches of the recurrent laryngeal nerve (RLN) in decerebrate, vagotomized, paralyzed, ventilated cats. Activities of the whole RLN and phrenic nerve were also recorded. Nerve activities were assessed at several steady-state end-tidal O2 and CO2 concentrations. The nerve to the thyroarytenoid (TA) muscle, a vocal cord adductor, was only slightly active under base-line (normocapnic, hyperoxic) conditions but in most cats developed strong activity during expiration in hypocapnia or hypoxia. In severe hypocapnia, phasic expiratory TA activity persisted even during phrenic apnea, indicating continuing activity of the respiratory rhythm generator. The nerve to the posterior cricoarytenoid (PCA) muscle, the vocal cord abductor, was always active in inspiration but often showed expiratory activity as well. This expiratory activity was usually enhanced by hypercapnia and often inhibited by hypoxia. The results are consistent with previous electromyographic findings and emphasize the importance of distinguishing abductor from adductor activity in studies of laryngeal control.

Efferent activities on the phrenic and recurrent laryngeal (RLN) nerves were monitored during eupnea, apneusis, and gasping in decerebrate, paralyzed, and ventilated cats before and after spinal cord transection at the first cervical level. The vagi were sectioned caudal to the RLN being studied and at the midcervical level contralaterally. Before spinal transection, the onset of RLN inspiratory activity preceded that of the phrenic nerve during eupnea and apneusis; in gasping, phrenic activity began before the RLN. These results were the same in normocapnia, hypercapnia, and hypoxia. After spinal transection, no phasic phrenic activity was observed at normoxia or hyperoxia, whereas the RLN exhibited discharge patterns similar to those before transection. Upon end-tidal O2 partial pressure diminutions below 50 Torr, one or more "burst" of phrenic activity were recorded. These bursts were not synchronized with the phasic RLN discharge. It is concluded that automatic ventilatory activity may be generated by inherent brain stem mechanisms. These results further imply the processes underlying gasping neurogenesis may differ fundamentally from those of eupnea or apneusis.

The steady-state ventilatory and end-tidal PCO2 (PETCO2) responses to low-level CO2 inhalation have been studied in four awake cats. Four cats anesthetized with Dial-urethane were also studied before and after vagal section or blockade. Awake cats breathed gas mixtures with FICO2 equal to 0.0015 (control), 0.01 and 0.03 in oxygen or 0.0015, 0.01 and 0.02 in air, while anesthetized cats inhaled FICO2 of 0.0000 (control), 0.005 and 0.01 in oxygen. In order to obtain accurate, unbiased determinations of the respiratory system responses to small increases of FICO2 above control values, we used a protocol in which control conditions preceded and followed each CO2 test. The pairwise response for each variable was calculated from the mean of the two 'bracketing' control values. We found that low-level CO2 inhalation in the cat resulted in consistent and significant increases in PETCO2 (82 of 86 trials) and VT (76 of 86 trials) but inconsistent changes in TTOT. We conclude that low-level CO2 inhalation in the cat results in hypercapnia detectable by a replicated, unbiased experimental design.

Ventilation, laryngeal resistance and electromyograms of the diaphragm, posterior cricoarytenoid (PCA) and thyroarytenoid (TA) muscles were recorded in anesthetized, spontaneously breathing cats during 100% O2 administration and during steady state inhalation of hypercapnic and hypoxic gas mixtures. As shown previously, hyperoxic hypercapnia lowered expiratory laryngeal resistance (RlarE). Isocapnic hypoxia also lowered RlarE, and hypercapnia superimposed on hypoxia decreased it further. Hypocapnia raised RlarE. Changes in inspiratory laryngeal resistance (RlarI) were similar to those in RlarE, but smaller. When ventilation was stimulated to the same extent by hypoxia and by hypercapnia, RlarE was lower under hypoxic than hypercapnic conditions in most animals. The electromyograms showed that the respiratory oscillations in laryngeal resistance and the laryngeal responses to hypercapnia and hypoxia were determined chiefly by the activity of the PCA muscle, the abductor of the vocal cords. The TA-a representative adductor muscle-was silent under all conditions studied. The results, considered with previous work, indicate that the larynx plays a part in determining the breathing pattern under resting conditions and during respiratory stimulation by hypercapnia and hypoxia.

In decerebrate, vagotomized, paralyzed, and ventilated cats, activities of the phrenic nerve and single hypoglossal nerve fibers were monitored. The great majority of hypoglossal neuronal activities were inspiratory (I), discharging during a period approximating that of phrenic. Many were not active at normocapnia but were recruited in hypercapnia or hypoxia. Once recruited, discharge frequencies, which rose quickly to near maximal levels in early to midinspiration, significantly increased with further augmentations of drive. Also, the onset of activities became progressively earlier, compared with phrenic discharge, in hypercapnia or hypoxia. Smaller numbers of hypoglossal fiber activities, having inspiratory-expiratory (I-E), expiratory (E), expiratory-inspiratory (E-I), or tonic discharge patterns, were also recorded. Activities of E, I-E, and those I fibers that became I-E in high drive may underlie the early burst of expiratory activity of the hypoglossal nerve. It is concluded that the firing and recruitment patterns of hypoglossal neurons differ from those of phrenic motoneurons. However, responses to chemoreceptor stimuli are similar among the two neuronal groups.

Alcohol consistently decreases genioglossal electromyographic (EMG) activity in awake men, but in women this response is more variable, possibly because of the menstrual cycle. To assess the interaction between alcohol and the menstrual cycle on genioglossal EMG activity, we measured ventilation and genioglossal EMG activity in 9 normal women before and after they drank 1 ml/kg alcohol. The effect of alcohol on ventilation and genioglossal EMG activity was studied twice in each subject: once during the follicular phase and again during the luteal phase of the menstrual cycle. Measurements were made while the subjects breathed room air and rebreathed a hypercapnic gas mixture. The ventilatory response to CO2 was significantly greater during the luteal phase of the menstrual cycle. Alcohol had no effect on resting ventilation or the ventilatory response to CO2 during either phase of the menstrual cycle. However, alcohol significantly decreased peak integrated genioglossal EMG activity during the follicular (low progesterone) phase but not during the luteal (high progesterone) phase of the cycle. The relative alcohol resistance of genioglossal EMG activity during the luteal phase may explain in part the low incidence of sleep-disordered breathing in premenopausal women and the benefit that some male patients with obstructive sleep apnea have derived from treatment with progesterone.

Five healthy young subjects were studied to assess the changes in vocal cord movements that occur between resting breathing and hyperpnea. Both hypercapnia and exercise induced decreases in the extent of narrowing of the glottic aperture occurring during expiration. In addition, four of the subjects showed a significant positive rank correlation between the extent of narrowing of the glottis and the observed length of the expiratory phase of the respiratory cycle. These results indicate that the braking of expiratory airflow by movements of the vocal cords toward the midline is reduced during hyperpnea at the same time that expiratory time is decreased.

We measured respiratory airflow and intrapulmonary pressure in spontaneously breathing garter snakes (Thamnophis sirtalis) before and after bilateral vagotomy. Each breathing cycle consisted of expiration, inspiration, and a breath-holding period with the glottis closed, as previously reported. Respiratory system compliance was very high compared with that of mammals (0.042 ml/cm H2O per g), but was considerably reduced when the animal was coiled. Resistance to airflow averaged 6.35 cm H2O per ml/sec. Lung volume during the breath-hold was usually above the relaxed volume of the system. Analysis of dynamic pressure-volume and flow-volume loops showed that both expiration and inspiration were active, and that little use was made of passive recoil pressure in expiration. Evidence that vagally mediated, volume-related feedback influenced the breathing pattern was found in some snakes, but this influence was weaker than in most mammals and other reptiles. The results suggest that breathing in snakes is mainly a centrally programmed process, not markedly dependent on respiratory system mechanics or neuromechanical feedback. This arrangement is advantageous in view of the high, posturally variable compliance and the frequent regional distortions of the respiratory system that result from the unique structure of these animals.

Anesthetic and sedative drugs have been found to diminish the respiratory motor activity of the hypoglossal nerve more than that of the phrenic nerve. This differential depression of motor activity to the upper airway may contribute to the exacerbation of obstructive sleep apnea by sedative drugs. To determine whether morphine has a similar selective action, we recorded phrenic and hypoglossal nerve activities before and after morphine administration in decerebrate, vagotomized cats, paralyzed with gallamine. Morphine diminished the activities of both nerves in most animals, but the responses were highly variable, and no consistent pattern of differential depression was apparent. The variability of the results may reflect the complex nature of opiate actions on the control of breathing.

The purpose of this study was to assess the influence of pulmonary inflations on activities of single phrenic motoneurons. Studies were performed in decerebrate and paralyzed cats; activities of phrenic nerve and single phrenic motoneurons were recorded. Animals were ventilated with a servo-respirator which produced alterations in tracheal pressure in parallel with changes in integrated activity of the phrenic nerve. At end-tidal fractional concentrations of CO2 of 0.05, phrenic motoneurons were distributed into "early" and "late" populations, depending on time of onset of activity. During the late stages of neural inspiration, differences in levels of integrated activity of the phrenic nerve became evident between cycles with and without lung inflations. At a time approximating 90% of the inspiratory duration during inflations, integrated phrenic activity was higher for cycles with inflation. Concomitantly, with lung inflations, the discharge frequencies of early phrenic motoneurons were lower, and late motoneurons began to discharge sooner than when inflations were withheld. Similar results were obtained in hypercapnia. We conclude that reflexes activated by pulmonary inflations may produce augmentation, as well as inhibition of phrenic motoneuronal activities. Factors responsible for eliciting these reflex augmentations and inhibitions are discussed.