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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.

Since stimuli from abdominal or pelvic viscera can affect respiratory muscle function, we hypothesized that mechanical stimulation of the gallbladder would result in inhibition of motor activity to the diaphragm and to upper airway muscles. We studied 12 decerebrate, vagotomized, paralyzed, artificially ventilated cats and recorded hypoglossal (HG) and phrenic (PHR) nerve activities while applying 600-1000 g of traction on the gallbladder during four respiratory cycles. Traction resulted in an initial reduction of PHR activity to 87.6+/-15.0% (mean+/-S.D.% of its baseline value), a reduction of HG activity to 74.2+/-27.5% and a lengthening of expiratory time to 178.8+/-81.0%. Subsequently, PHR activity and expiratory time returned toward control values, while HG remained diminished, at 66.4+/-19.1%. Our results show that mechanical stimulation of the gallbladder results in a respiratory inhibition with a disproportionate reduction in HG activity relative to PHR discharge. We speculate that gallbladder stimulation by contractions or surgery may compromise breathing by inhibition of phrenic discharge and upper airway obstruction.

Spontaneous contractions of the urinary bladder (SBCs) and experimental elevations of carotid sinus pressure (CSP) have been shown to result in respiratory inhibition with preferential reduction in hypoglossal (HG) nerve activity as compared with that of phrenic nerve discharge. We assessed the interaction between these respiratory inhibitory stimuli in decerebrate, vagotomized, paralyzed and artificially ventilated cats. We denervated the right carotid sinus and pressurized the isolated left carotid sinus region within the linear range of the baroreflex, while maintaining systemic arterial pressure at approximately 100 mmHg. We monitored the HG and phrenic nerve responses to SBCs, to elevations in CSP between SBCs, and to elevations in CSP during SBCs. Our results show that superimposing these stimuli results in respiratory inhibition, especially of HG activity, that exceeds that resultant from either stimulus alone. We speculate that the combined presence of SBCs and episodic hypertension may contribute to the development of periodic breathing or obstructive apnea, particularly during sleep.

Spontaneous contractions of the urinary bladder (SBCs) have been shown to decrease the frequency and depth of respiration in anesthetized or unanesthetized, decerebrate cats. The respiratory responses to bladder voiding reflexes in the awake state have not been previously addressed. Because a chronic rat model for the study of bladder function has been established and breathing measurements can be made in the awake rat, we chose the rat as an experimental model to assess whether SBCs would alter breathing in the conscious, intact animal. Respiratory frequency increased during bladder contractions but tidal volume remained unaffected. To assess whether the respiratory response to bladder reflexes in rats differed from that previously observed in cats, we also studied decerebrate, vagotomized, paralyzed and artificially ventilated rats. Contrary to the respiratory inhibition observed in decerebrate cats, phrenic and hypoglossal nerve activities remained unaffected during SBCs in decerebrate rats. These results indicate a species difference in the coupling between respiration and bladder voiding reflexes.

Gradual distension of the urinary bladder evokes spontaneous bladder contractions (SBCs), which are associated with reduced inspiratory activity in the phrenic and other inspiratory motor nerves. We examined the influence of isovolumetric SBCs on the threshold for termination of phrenic inspiration by electrical stimulation of superior laryngeal and/or mid-thoracic intercostal nerves (ICN) in decerebrate, vagotomized, paralyzed, ventilated cats. Although SBCs reduced phrenic inspiratory activity, the threshold for inspiratory termination by nerve stimulation was increased. The results emphasize the complexity of the synaptic connections among brain stem neurons governing micturition and breathing.

Airway obstruction at the level of the larynx causes respiratory insufficiency during experimental seizures in spontaneously breathing, anesthetized piglets (T. E. Terndrup and W. E. Fordyce, Pediatr. Res., 38: 61-66, 1995). To investigate further the neural mechanisms of this obstruction, the activities of the phrenic nerve (PH) and the recurrent laryngeal motor branches to the thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles were analyzed in 11 anesthetized, vagotomized, paralyzed, and ventilated piglets. After a control recording period, seizures were induced by subcortical penicillin G injections. Compared with baseline conditions, nerve activities became irregular during seizures. Extraneous TA bursts during PH activation were evident in all piglets during seizures. During ictal phases of seizures, the peak integrated activities of the PH and the expiratory component of the PCA, but not TA or inspiratory PCA activities, were significantly decreased compared with interictal phases. During seizures, a significant delay in the onset of the inspiratory component of PCA activation with respect to the onset of the PH was observed. This study helps to explain respiratory impairment during cortical seizures by providing evidence of impaired timing of activation of laryngeal dilator mechanisms and coordination with those activating the diaphragm. Cyclical PH inhibition during high-intensity cortical discharges may provide a secondary mechanism producing respiratory insufficiency during seizures.

Spontaneous bladder contractions (SBCs) in decerebrate, vagotomized, paralyzed, ventilated cats have been shown to decrease phrenic and hypoglossal inspiratory nerve activities, as well as the activities of other respiratory motor nerves. To determine whether vagal afferents from the lung influence the respiratory inhibition associated with SBCs, we recorded phrenic and hypoglossal nerve activities in decerebrate, paralyzed, vagally intact cats. The animals were ventilated by a servo-respirator, which inflated the lungs in accordance with integrated phrenic nerve activity. Maintained increases in end-expiratory lung volume were produced by the application of 2-10 cm H2O positive end-expiratory pressure (PEEP). SBCs were accompanied by decreases in both phrenic and hypoglossal peak integrated nerve activities, as well as by marked decreases in respiratory frequency. The reduction of respiratory frequency was greater with higher levels of PEEP, a few animals becoming apneic during SBCs. After bilateral vagotomy, SBCs continued to decrease phrenic and hypoglossal peak integrated nerve activities as previously reported, but the reduction of respiratory frequency was much less striking than when the vagi were intact. These results indicate that activity of vagal afferents from the lung augments the respiratory influence of SBCs. Furthermore, SBCs in vagally intact animals can induce periodic breathing.

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.

Responses of laryngeal receptors selected for their responsiveness to 10% intralaryngeal CO2 were recorded in single fibers of the superior laryngeal nerve at a wide range of systemic PCO2 values and before and after carbonic anhydrase inhibition in anesthetized, paralyzed, ventilated cats. Carbonic anhydrase was inhibited, locally, by perfusing the upper airways with either acetazolamide or methazolamide (10(-2) M) or systemically, by injecting acetazolamide intravenously (5, 10, or 25 mg/kg). Of the 58 receptors studied, 55 decreased their discharge rate in response to 10% intralaryngeal CO2, whereas 3 increased their discharge in response to intralaryngeal CO2. The majority of these receptors also increased their discharge rate in response to positive laryngeal pressure. Neither increased nor decreased systemic PCO2 influenced the receptors' baseline discharge rate or their response to intralaryngeal CO2. Topical inhibition of carbonic anhydrase did not consistently alter the maximal inhibitory response to CO2 or the initial rate of change of receptor activity. On the other hand, intravenous injections of acetazolamide caused, within 30 sec, a consistent attenuation of both the initial rate of change and the maximal inhibitory response to intralaryngeal CO2. These results indicate that the sub-set of laryngeal receptors that are sensitive to intralaryngeal CO2 are not responsive to changes in systemic PCO2. The carbonic anhydrase inhibition experiments show that this enzyme plays an important role in the ability of these receptors to detect both transient and steady-state changes in intralaryngeal CO2.

We evaluated respiratory motor nerve activities during experimental seizures induced with subcortical penicillin. The activities of the phrenic (PH), nasolabial (NL), and hypoglossal (HG) nerves and the recurrent laryngeal motor branches to the thyroarytenoid (TA) and posterior cricoarytenoid (PCA) muscles were analyzed in 13 anesthetized, vagotomized, paralyzed, and ventilated cats. During ictal and interictal phases of seizures, nerve activities became irregular and peak integrated nerve activities increased, particularly in the case of the PH nerve. The ictal phase of seizures was associated with increased tonic activity and decreased phasic respiratory discharges, particularly in the cases of the HG, NL, and PCA nerves. During some prolonged ictal discharges, entrainment of nerve activities by cortical spiking was associated with irregular uncoordinated activation, particularly in the TA nerve. These studies help explain respiratory impairment during seizures by providing evidence of impaired coordination between activation of muscles that regulate upper airway patency and activation of the diaphragm.

We monitored spontaneous bladder contractions (SBCs) in decerebrate vagotomized paralyzed ventilated cats while recording respiratory motor nerve activities and intravesical pressure under isovolumetric conditions. Phrenic nerve discharge diminished during SBCs, as did the activities of the hypoglossal nerve, the nasolabial branch of the facial nerve, and inspiratory (posterior cricoarytenoid) and expiratory (thyroarytenoid) branches of the recurrent laryngeal nerve. Hypoglossal activity was most strikingly reduced during SBCs, disappearing completely in some animals. The triangularis sterni nerve exhibited an initial decrease, followed by an increase in activity during SBCs, whereas the cranial iliohypogastric nerve showed increased activity. The changes in nerve activities during SBCs could also be elicited by passive distension of the bladder and were abolished by bilateral section of the pelvic nerves. These findings extend the understanding of reflexes originating from the urinary bladder to include a coordinated respiratory response and suggest that these reflexes may compromise upper airway patency under some conditions.

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.

We examined the relationship between hypoglossal and phrenic nerve activities and carotid sinus pressure. In 12 adult cats that were decerebrate, vagotomized, paralyzed, and mechanically ventilated, we isolated the left carotid sinus for perfusion and denervated the right carotid sinus. Mean arterial blood pressure was maintained at 90-100 mmHg using a low resistance-reservoir containing saline and connected to the abdominal aorta. Constant pressure was applied to the carotid sinus region. We found that increased carotid sinus pressure immediately inhibited inspiratory-synchronous (phasic) hypoglossal nerve activity and that there was a direct inverse relationship between phasic hypoglossal activity and carotid sinus pressure up to a carotid pressure of 285 mmHg. Increased carotid sinus pressure had no effect on tonic hypoglossal nerve activity and only slightly inhibited phrenic nerve activity. Cutting the left carotid sinus nerve abolished this response. We also applied pressure pulses to the carotid sinus at discrete times during the phrenic cycle. We found that baroreceptor inhibition of phasic hypoglossal nerve activity was gated during the phrenic cycle: maximum inhibition occurred when the pulse was applied in late expiration. We conclude that carotid baroreceptor stimulation preferentially inhibits inspiratory synchronous hypoglossal nerve activity and that this afferent information traveling in the carotid sinus nerve is gated by the respiratory control center.

Increased blood pressure (BP) leads to inhibition of respiratory activity of hypoglossal nerve in anesthetized cats, implying that arterial baroreceptor activity may inhibit upper airway motor outputs. We examined the effect of passive tilt on upper airway muscle activity in men under the assumption that changes in degree of tilt would change local pressure at the carotid baroreceptors. We also examined the possibility that inhibition of upper airway muscle activity occurred secondary to a decrease in level of arousal. In seven normal awake adult males, we measured electromyogram activity of the genioglossus (EMGge), electroencephalogram (EEG), electrocardiogram, ventilation, end-tidal fractional concentration of CO2, and BP while the subject was on a tilt table wearing inflatable antishock pants. Three tilt table positions were used: 60 degrees head-up (60 degrees increases), supine (S), and 30 degrees head-down (30 degrees decreases), with pants either deflated (P-) or inflated (P+) to 40 mmHg. During P-, moving the subject from 60 degrees increases to S to 30 degrees decreases positions resulted in steady-state heart rates of 94.8 +/- 1.7, 66.9 +/- 0.7, and 68.9 +/- 0.8 beats/min and EMGge activities of 54.4 +/- 4.4, 37.7 +/- 2.0, and 31.5 +/- 2.4% of maximum, respectively. During P+, changes in heart rate were similar but significantly reduced from P-, and positional changes in EMGge were eliminated. The level of arousal was unchanged. The transient response of EMGge to tilt was biphasic: when moving from upright to supine position, there was a rapid increase in activity during the tilt maneuver followed by a progressive decline.(ABSTRACT TRUNCATED AT 250 WORDS)

Intralaryngeal CO2 in decerebrate, vagotomized cats decreases phrenic nerve activity and increases the respiratory activity of the hypoglossal (HG) nerve. These responses are mediated by afferents in the superior laryngeal nerves. To explore the responses of other respiratory motor nerves to this stimulus, we have recorded the activities of the nasolabial (NL) branch of the facial nerve, the posterior cricoarytenoid (PCA) and thyroarytenoid (TA) branches of the recurrent laryngeal nerve and the nerve to triangularis sterni (TS) muscle. In response to 5 and 10% CO2 in the surgically isolated upper airway, we found dose-related decreases in phrenic activity, increases in HG and NL activity and characteristic, but intermittent, exaggeration of early expiratory bursts of TA activity. The activities of the PCA and TS nerves showed no consistent responses. These results broaden the definition of the reflex response to intralaryngeal CO2, revealing components that reflect ventilatory inhibition, upper airway dilation and laryngeal protection.

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.

1. We recorded afferent activities of single fibres in the superior laryngeal nerves of decerebrate or anaesthetized, paralysed cats while 3, 5 and 10% CO2 was added to a constant flow of warm, humidified air through the isolated upper airway. 2. Fifty-three receptors with discharge frequencies modulated by intralaryngeal CO2 were studied. Of these, forty-eight showed CO2-induced attenuation of their firing rates. Pulses of 3, 5 or 10% CO2, alternating with air at intervals ranging from 1.5 to 60 s, also diminished the discharge frequencies. This diminution was greater with higher CO2 concentrations and longer pulse durations. 3. Five of the fifty-three receptors were stimulated by intralaryngeal CO2. The discharge frequencies of these units increased slowly and by only a few impulses per second during CO2 exposure. 4. Thirty-four of the CO2-sensitive receptors were tested with other stimuli, including water, saline, positive and negative intralaryngeal pressures and cold air. The responses to these stimuli varied among receptors, but many of the units that reduced their frequencies with intralaryngeal CO2 were consistently stimulated by positive and/or negative intralaryngeal pressures. 5. Thirty-six of the receptors were anatomically located by probing the upper airway. Twenty-six were in the larynx, and ten were in the rostral trachea, within 5 mm of the cricoid cartilage. 6. The results, which are directly applicable to the investigation of reflex responses reported in the preceding paper, indicate that the predominant initial response to intralaryngeal CO2 under the conditions of these studies is attenuation of laryngeal receptor activity.

We investigated the quantitative relationships among pharyngeal resistance (Rph), genioglossal electromyographic (EMGge) activity, nasal resistance (Rna), and airflow in 11 normal men aged 19-50 while they were awake. We made measurements with subjects seated with the head erect, seated with the head flexed forward approximately 40 degrees, and supine. Each subject wore a face mask connected to a pneumotachograph to measure airflow. After topical anesthesia of the nose, two catheters for measuring nasal and pharyngeal airway pressures were passed through one nostril: the nasal pressure catheter was positioned at the nasal choanae, and the pharyngeal pressure catheter was positioned just above the epiglottis. We measured EMGge activity with an intraoral surface electrode. The subjects breathed exclusively through the nose while inhaling room air or rebreathing CO2. We measured Rph, Rna, airflow, and EMGge activity at approximately 90-ms intervals throughout each inspiration. Rph was invariant as head position was changed. At any given head position, EMGge activity rose as airflow increased, and Rph remained constant. In contrast, Rna increased as airflow increased. Because Rph was constant, EMGge activity was not correlated with Rph, but EMGge was positively correlated with Rna and airflow. On the basis of the stability of Rph in the face of marked changes in collapsing forces, we conclude that the dynamic interplay of posture, head and jaw position, and upper airway muscle activity quite effectively maintains pharyngeal patency, and interactions among these factors are subtle and complex.

Cold air flowing through the larynx is known to alter the activities of laryngeal receptors with afferents in the superior laryngeal nerves (SLNs) and to induce reflex apnea in neonatal mammals. To examine the ventilatory response in adult animals and to explore associated upper airway motor responses, we recorded phrenic and hypoglossal neural responses to cooling the isolated larynx with cold air in decerebrate, vagotomized, paralyzed, ventilated cats. The most consistent response was phrenic inhibition, which occurred in all animals tested. Either excitation or inhibition of hypoglossal activity was seen consistently in individual cats, with the result that the group response was not statistically significant. All responses to laryngeal cooling were abolished by section of the SLNs. The findings confirm that directing cold air through the larynx causes reflex inhibition of ventilatory (phrenic) activity, but raise new questions as to how the two, directionally opposite hypoglossal responses are mediated.

We studied the effects of systemically administered ethyl alcohol on the respiratory motor activity of the phrenic, hypoglossal and recurrent laryngeal nerves in unanesthetized, decerebrate cats. Some of the cats were studied after carotid sinus nerve section. In addition, parallel studies were done in intact, awake cats with chronic electromyographic electrodes in the diaphragm, genioglossus, and posterior cricoarytenoid (PCA) muscles. In decerebrate animals, alcohol induced a significant reduction of hypoglossal and recurrent laryngeal nerve activities at doses that had little or no effect on the phrenic nerve discharge. Similar changes were observed in chemodenervated cats. In awake animals, genioglossal and PCA muscle activities were depressed by alcohol, whereas diaphragm activity showed no consistent change. Alcohol caused a significant increase in respiratory frequency in awake cats and reduced the responses of genioglossal and PCA muscle activities to hypercapnia and normocapnic hypoxia. We conclude that alcohol induces a selective reduction in upper airway respiratory motor activity by an action that does not require intact suprapontile structures, vagal afferents, or peripheral chemoreceptors. This reduction may contribute to the alcohol-induced exacerbation of obstructive sleep apnea.

We have developed a new technique for diaphragmatic electromyography using an array of seven sequential electrode pairs at 1.0-cm spacing on an esophageal catheter. This array provides information about the spatial distribution of the electrical field generated by the diaphragm and reveals a sharply peaked variation of electrical potential with distance along the esophagus. The rectified and integrated information from each of the seven pairs is summed to give an approximation to the total electrical activity over the span of the array, providing a signal that is relatively insensitive to the position of the array over approximately 4 cm of catheter movement and removes the requirement for balloon stabilization of the catheter. With our array, we have confirmed the artifact in the evoked compound muscle action potential that seems to be related to diaphragmatic shape as reported by others who used supramaximal phrenic nerve stimulation, but the magnitude of this artifact (compared with the functional residual capacity level) was modest near functional residual capacity, averaging 12 +/- 14% (SD) for lung volumes 1.0 l above and -4 +/- 15% for lung volumes 1.0 l below functional residual capacity along the rib cage-abdomen relaxation line.

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.

We recorded ventilation and genioglossal electromyographic activity in 12 awake, normal subjects before and after they drank 1 ml of ethyl alcohol per kg of body weight. Measurements were made during quiet room air breathing and during hypercapnic rebreathing. Alcohol did not alter minute ventilation, the pattern of breathing, or the ventilatory response to CO2, but it significantly reduced genioglossal activity in both quiet breathing and hypercapnia. The effect was more consistent in male than in female subjects. These results indicate that the neural mechanisms underlying the respiratory activity of the genioglossus are more susceptible to depression by alcohol than those serving the muscles of the ventilatory pump. This susceptibility may be important in the exacerbation by alcohol of obstructive apnea during sleep.

We have developed an intraoral bipolar surface electrode for the genioglossus muscle. The electrode, made from an athletic mouthguard and dental impression material, was fitted to the lower teeth. Electrode wires, bared at the tip, were positioned on the bottom of the mouthpiece to lie in contact with the superior surface of the genioglossus just behind the teeth. The electromyographic activity of the genioglossus, simultaneously obtained from the surface electrode and conventional intramuscular electrodes, was compared during quiet breathing, CO2 rebreathing, and a variety of tongue movements. The two types of electrodes recorded similar patterns of muscle activity, and spectral analyses of the signals revealed similar and highly coherent frequency spectra. We conclude that the surface electrode satisfactorily reflects the bioelectrical activity of the genioglossus. The mouthpiece electrode has the further advantage that quantitative comparisons can be made among recordings made in different experimental sessions, since the fit of the mouthpiece to the teeth assures a constant relationship of the electrode to the genioglossus muscle.

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.

Sedative drugs have been found to depress the respiratory activity of upper airway muscles more than that of the diaphragm. To determine whether CO2 at narcotic levels has a similar action, we recorded phrenic and hypoglossal nerve activities in decerebrate, vagotomized, paralyzed cats. T5 or T6 external intercostal nerve activity was also recorded in some animals. End-tidal CO2 concentration was raised progressively to over 30% or until depression of nerve activity was apparent. Respiratory frequency was reduced by severe hypercapnia in most cats. Hypoglossal nerve activity was consistently decreased more than that of the phrenic nerve. In most cases intercostal nerve activity was also more susceptible than phrenic nerve activity to hypercapnic depression. The results indicate that CO2 at narcotic levels interferes both with the central pattern generator for breathing movements and with the expression of the pattern in specific motor nerves.

The influence of head position on the respiratory activity of the diaphragm (DIA), posterior cricoarytenoid (PCA) and genioglossus (GG) muscles was studied in conscious cats with chronically implanted electromyographic electrodes. Tracheal pressure was also recorded through a small implanted catheter. Spontaneous or passive downward movements of the head resulted in sustained increases in the respiratory excursions of tracheal pressure and in PCA and GG activities. Conversely, these variables all decreased when the head was raised. Activity of the DIA was little affected. In animals with chronic tracheostomies, which greatly diminished tracheal pressure excursions and their changes with head movements, the postural responses of PCA and GG activities persisted, but were attenuated. The responses also persisted after bilateral superior laryngeal nerve section. These findings demonstrate responses that act to maintain the patency of the upper respiratory tract, probably by reflex mechanisms. Receptors in the upper airway contribute to the responses, but other afferents - possibly from vestibular or joint receptors - are also involved.

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.

To determine whether the central respiratory drives to costal and crural portions of the diaphragm differ from each other in response to chemical and mechanical feedbacks, activities of costal and crural branches of the phrenic nerve were recorded in decerebrate paralyzed cats, studied either with vagi intact and servo-ventilated in accordance with their phrenic nerve activity or vagotomized and ventilated conventionally. Costal and crural electromyograms (EMGs) were recorded in decerebrate spontaneously breathing cats. Hypercapnia and hypoxia resulted in significant increases in peak integrated costal, crural, and whole phrenic nerve activities when the vagi were either intact or cut. However, there were no consistent differences between costal and crural neural responses. Left crural EMG activity was increased significantly more than left costal EMG activity in response to hypercapnia and hypoxia. These results indicate that the central neural inputs to costal and crural portions of the diaphragm are similar in eupnea and in response to chemical and mechanical feedback in decerebrate paralyzed cats. The observed differences in EMG activities in spontaneously breathing animals must arise from modulation of central respiratory activity by mechanoreceptor feedback from respiratory muscles, likely the diaphragm itself.

Sleep deprivation appears to increase the severity of obstructive sleep apnea, and inadequate activation of the genioglossus muscle may play an important role in the pathogenesis of obstructive sleep apnea. Therefore, we investigated the effect of sleep deprivation on genioglossal electromyographic (EMG) activity. Eleven men were studied during room air breathing and CO2 rebreathing before sleep deprivation (control), after 1 night of sleep deprivation, and the day after sleep recovery. We measured inspired minute ventilation, tidal volume, respiratory frequency, and peak integrated inspiratory genioglossal EMG activity. After sleep deprivation, no significant changes in inspiratory minute ventilation or tidal volume occurred during room air breathing or CO2 rebreathing, but the breathing frequency during CO2 rebreathing increased significantly after sleep deprivation. Genioglossal EMG activity was diminished during CO2 rebreathing after sleep deprivation, but this was significant only in subjects 30 yr of age and older. The fall in EMG activity was independent of changes in tidal volume. All variables returned towards control levels after sleep recovery. We conclude that sleep deprivation selectively decreases genioglossal EMG activity during CO2 rebreathing in awake older subjects. This influence of sleep deprivation may play a role in the pathogenesis or severity of obstructive sleep apnea.

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.

Electromyographic patterns of the diaphragm and a posterior cricoarytenoid (PCA) muscle were evaluated in anesthetized rabbits with and without reversible blockade of pulmonary stretch receptors by inhalation of 200 ppm sulfur dioxide (SO2). Inspiratory activity of both muscles was increased by hypercapnia and by isocapnic hypoxia, with or without receptor blockade. Expiratory diaphragmatic activity was diminished by these stimuli and was likewise not qualitatively affected by SO2 exposure. Expiratory PCA activity was increased by hypercapnia and hypoxia prior to SO2 exposure, but decreased by these stimuli during stretch receptor blockade. These results are consistent with the previous finding that vagal afferents facilitate expiratory PCA activity, thus maintaining a patent laryngeal airway, even in the face of increased carotid chemoreceptor afferents, which inhibit expiratory activity of the PCA muscle. The results further indicate that some or all of the afferents responsible for this effect are from pulmonary stretch receptors.

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.

Distention of the esophagus has been shown to result in selective inhibition of phasic inspiratory activity in the crural portion of the diaphragm, with no effect on costal diaphragmatic activity. The purpose of this study was to determine rigourously the afferent pathways that mediate this response. Bipolar EMG electrodes were placed in the costal and crural portions of the diaphragm in decerebrate, spontaneously breathing cats. Distention of the esophagus by inflation of a Foley catheter balloon with 20 ml of air resulted in a selective inhibition of crural hiatal EMG activity, while costal EMG activity was maintained at predistention levels. The distention was accompanied by a reduction in respiratory frequency. Transection of the spinal cord at the C8-T1 level did not obliterate the crural inhibition produced by inflation. Section of the C4-C8 dorsal roots also failed to abolish the response. However, after bilateral cervical vagotomy, esophageal distention no longer influenced diaphragmatic EMG activity. These results indicate that the crural inhibition observed with esophageal distention is vagally mediated and is not influenced importantly by intercostal or phrenic afferents. Records of activity of the phrenic nerve branch innervating the crural portion of the diaphragm showed a similar response pattern, confirming that the inhibition is central in origin and that the crural fibers inhibited by distention are only a fraction of the total population of crural phrenic motoneurons.

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.

We examined the effect of diazepam on the respiratory electromyographic (EMG) activity of the genioglossal muscle using a double-blind, placebo-controlled, randomized protocol. Control measurements of minute ventilation, tidal volume, frequency, end-tidal CO2, and peak integrated inspiratory genioglossal EMG activity were made in 10 normal awake male subjects during quiet breathing and CO2 rebreathing. Subjects then received either 10 mg of diazepam orally or a placebo, and all respiratory measurements were repeated after 45 min. Each subject was studied on 2 separate days, receiving each treatment on a different day. The placebo had no effect on any of the measured variables. After diazepam, we observed an increase in end-tidal CO2 rebreathing, diazepam was associated with a reduction in minute ventilation, tidal volume, and frequency. When compared at equal end-tidal CO2 levels, genioglossal EMG activity and tidal volume were significantly reduced after diazepam. However, only older subjects demonstrated a reduction in EMG activity when compared at equal tidal volumes during CO2 rebreathing. We conclude that diazepam selectively decreases genioglossal EMG activity during CO2 rebreathing only in older subjects.