Effects of carotid denervation on interactions between lung inflation and PaCO2 in modulating phrenic activity

Hypercapnia attenuates the effects of static airway pressure (Paw) on phrenic burst frequency (f) and the expiratory duration. We examined the role of carotid chemoreceptors in this response using an experimental preparation that allowed independent control of lung inflation and CO2 reflexes. Experiments were conducted in intact (n = 6) and carotid denervated (CBX; n = 12) chloralose/urethane anesthetized dogs. Integrated phrenic amplitude (Phr), f, and the inspiratory (TI) and expiratory durations (TE) were measured as a function of Paw (2-12 cm H2O) at levels of PaCO2 between 30 and 80 mm Hg. In intact dogs: (1) f decreased as Paw increased, and elevated PaCO2 decreased the slope of this relationship; (2) neither PaCO2 nor Paw affected TI; and (3) TE increased hyperbolically with Paw, and elevated PaCO2 attenuated this relationship. In CBX dogs: (1) f decreased as Paw increased, but this relationship was not affected by PaCO2; (2) TI increased as PaCO2 increased but was unaffected by Paw; and (3) TE increased as Paw increased but was unaffected by PaCO2. The results indicate that carotid chemoreceptors are necessary in the mechanism whereby hypercapnia attenuates the effects of Paw on f and TE. Furthermore, carotid denervation reveals an effect of hypercapnia on TI, an effect that is not evident in dogs with functional carotid chemoreceptors.     

Effects of hypoxemia on phrenic nerve responses to static lung inflation in anesthetized dogs

To study interactions between hypoxemia and lung stretch in modulating ventilatory activity, an experimental preparation was used that allows independent control of static airway pressure (Paw) and arterial PO2 in anesthetized dogs. Phrenic burst frequency (f) and integrated amplitude (Phr) were monitored while Paw was varied between 2 and 12 cm H2O at levels of PaO2 between 30 and 200 mm Hg. Experiments were repeated in intact (n = 8) and carotid denervated dogs (CBX; n = 7). In intact dogs, f decreased with increasing Paw through an effect on the expiratory duration (TE). Hypoxia increased f by decreasing both the inspiratory duration (TI) and TE. Hypoxia had no effect on the slope of the f vs Paw relationship, but attenuated the effect of Paw on TE. Phr was increased by hypoxia, but Paw had little effect. After CBX, f was still inhibited by Paw, but PaO2 had no consistent effect on f, TI or TE at any level of Paw. Phr was inhibited by hypoxia after CBX, but Paw had no effect. The results indicate that Paw and PaO2 exert additive effects on f in anesthetized dogs. Hypoxia attenuates the effect of Paw on TE, which alone would attenuate the slope of the f vs Paw relationship. However, the effect of hypoxia on TI enhances the slope of the f vs Paw relationship, restoring a parallel shift. These effects are abolished by carotid denervation.     

The effect of lung mechanics on gas transport during high-frequency oscillation.

With the general aim of obtaining clinically relevant information on the use of high-frequency oscillation (HFO), we examined the effects of altering oscillatory frequency (f), tidal volume (VT), and mean airway pressure (Paw) on gas exchange in rabbits, both before and after altering the animal's pulmonary mechanics by saline induced lung injury. Twenty-seven combinations of f (5, 8, 12 Hz), VT (0.5, 1, 2 mL/kg), and Paw (5, 10, 13 cm H2O) were used. Acute pulmonary injury was induced by instilling 10 mL/kg of warm saline into the lung. Gas exchange was assessed by steady-state levels of arterial oxygen tension (PaO2) and carbon dioxide tension (PaCO2). Arterial PaO2 was independent of f or VT before or after lung injury; it was independent of Paw before injury but highly dependent on Paw after lavage. The difference was presumably related to lung volume recruitment. Arterial PaCO2 was dependent on f and VT but independent of Paw at any time. The relationship was modeled by the equation PaCO2 alpha fa. VTb where the exponents a = -0.4 and b = -0.6. Our technique of a standardized saline instillation gave a reproducible and stable model of lung injury. In damaged rabbit lungs the principles of HFO appear to be similar to conventional mechanical ventilation; oxygenation depends on Paw and inspired oxygen concentration, while CO2 removal is determined by f and VT.     

Temperature effects on pulmonary receptor responses to airway pressure and CO2 in Alligator mississippiensis

The effects of body temperature (Tb) on pulmonary stretch receptor (PSR) and CO2-sensitive intrapulmonary chemoreceptor (IPC) response characteristics may have important effects on ventilatory control in reptiles. In this study, three questions were addressed: (1) what are the effects of Tb on PSR and IPC responses to airway pressure (Paw) and lung CO2 (PCO2); (2) what are the effects of acute (less than 12 h) vs chronic (greater than 1 week) changes in Tb on both receptor groups; and (3) can predicted changes in the fractional dissociation of imidazole (alpha im), calculated via independent changes in Tb and PCO2, explain the CO2-sensitivity of either IPC or PSR? Single fiber PSR and IPC responses to Paw, PCO2 and Tb were determined in 11 anesthetized Alligator mississippiensis (pentobarbital; 30 mg/kg), acclimated at 20 degrees C (N = 5) or at 30 degrees C (N = 6). PSR activity increased as Paw increased at both Tb, but PSR activity and sensitivity to Paw were lower at 20 degrees C. The average Q10 was 2.1. Increasing inhaled CO2 from 1 to 7% decreased PSR activity by 27 +/- 6% at 20 degrees C and 18 +/- 5% at 30 degrees C. IPC activity decreased as PCO2 increased at both Tb, but IPC activity and sensitivity were reduced at 20 degrees C. The average Q10 was 3.2. Increasing Paw from 2 to 10 cm H2O had inconsistent effects on IPC activity. There were no differences between the effects of acute or chronic changes in Tb on either PSR or IPC responses. Predicted changes in alpha im could not explain the CO2-sensitivity of either IPC or PSR. We conclude that PSR and IPC adapt rapidly to Tb changes. The larger Q10 of IPC suggests that the relative role of IPC vs PSR in ventilatory control may be greater at elevated body temperatures.     

Influence of phasic volume feedback on abdominal expiratory nerve activity

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.     

Functions of the retrofacial nucleus in chemosensitivity and ventilatory neurogenesis

The hypothesis was evaluated that neurons within the retrofacial nucleus of medulla integrate afferent stimuli from the central chemoreceptors. In decerebrate, vagotomized, paralyzed and ventilated cats, activity of the phrenic nerve was monitored. Peak integrated phrenic activity increased in hypercapnia; the frequency of phrenic bursts typically declined slightly. The retrofacial nucleus was ablated by radio-frequency lesions or neurons within this nucleus were destroyed by microinjections of kainic acid. Results were similar following lesions or injections. Following unilateral ablations, peak phrenic activity was greatly reduced at normocapnia and hypercapnia; the frequency of phrenic bursts typically rose. Both frequency and peak phrenic activity fell further after the contralateral destruction with a cessation of all phasic phrenic discharge being observed in most animals. Injections of kainic acid in regions rostral, caudal or medial to the retrofacial nucleus produced no consistent changes in phrenic activity. We conclude that neuronal activities in the region of the retrofacial nucleus are important both in the integration of stimuli from the central chemoreceptors and in defining the discharge patterns of respiratory neurons.     

Activity of abdominal muscle motoneurons during hypercapnia.

Our purpose was to examine the influence of hypercapnia on the activity of motoneurons innervating the transversus abdominis and internal oblique abdominal muscles, and of integrated phrenic and abdominal motor nerve activities. Studies were done in nine adult cats that were decerebrated, vagotomized, thoracotomized, paralyzed and ventilated mechanically. Of 42 motoneurons examined, 24 showed strong respiratory modulation (RM neurons), with the discharge confined primarily to the central expiratory period. The remaining 18 motoneurons discharged tonically, and failed to show respiratory modulation even at increased levels of central respiratory drive. Hyperoxic hypercapnia augmented the activities of the phrenic and abdominal nerves and increased the early expiratory discharge frequency of the RM neurons. The hypercapnia-induced increase in firing frequency during early expiration was accompanied by a corresponding decline in late expiration, and a virtual abolition of the inspiratory activity in the few neurons that discharged in this phase under normocapnic conditions. Finally, hypercapnia induced an increase in the number of spikes generated during each expiratory period in about half of the RM neurons, whereas the remaining cells showed a decrease. Thus, the increased peak activity of the integrated whole abdominal nerve burst with hypercapnia was brought about by a shift in the temporal pattern of motoneuron firing, or by an increase in the number of spikes generated during the expiratory period. The steep rate of rise and the pronounced early expiratory peak observed in the integrated abdominal nerve burst during hypercapnia in this preparation are consistent with the increase in motoneuron firing frequency during the early stages of the expiratory phase.     

Influence of extreme hypercapnia on respiratory motor nerve activity in cats

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.     

Effects of intrapulmonary CO2 and airway pressure on pulmonary vagal afferent activity in the alligator

The effects of airway CO2 and pressure on pulmonary vagal afferent fibers were studied in seven anesthetized alligators Alligator mississippiensis, at room temperature (24 degrees C). Of 49 receptors which fired in phase with ventilation, 13 behaved like mammalian rapidly adapting pulmonary stretch receptors, 19 like mammalian slowly adapting pulmonary stretch receptors (PSR), and 17 like avian intrapulmonary CO2-sensitive chemoreceptors (IPC). PSR and IPC were positively localized to the lung by punctate stimulation or response to airway CO2 changes during pulmonary artery occlusion. PSR discharge frequency (fPSR) was measured at airway pressures (Paw) from 0 to 15 cm H2O at FICO2 = 0.01 in 14 receptors. fPSR increased in all receptors throughout the range of Paw studied. In 13 PSR, increasing FICO2 from 0.01 to 0.07 decreased fPSR 23 +/- 13% (+/- SEM) at Paw = 2 cm H2O and 14 +/- 7% at 15 cm H2O. IPC discharge frequency (fIPC) decreased as FICO2 increased and most discharged less than 1 sec-1 at FICO2 = 0.03. In 7 IPC at FICO2 = 0.01, increasing Paw from 2 to 15 cm H2O increased fIPC 17 +/- 5% after pulmonary artery occlusion demonstrating some mechanosensitivity in alligator IPC. Although both IPC and PSR showed mechanosensitivity and CO2-sensitivity, the two receptor types were distinct. PSR were 13 times more sensitive to Paw changes than IPC and IPC were 14 times more sensitive to FICO2 changes than PSR. We did not find any receptors with intermediate CO2- or mechanosensitivities that could represent a transitional form of receptor. These results predict that IPC and PSR may have different roles in reflex ventilatory control.     

The effects of hypercapnia and hypoxia on single hypoglossal nerve fiber activity

The respiratory related modulation of hypoglossal nerve activity has been studied at the single fiber level in cats under hyperoxic hypercapnia and hypoxic conditions and their conduction velocities determined. Changes in fiber activity were compared to simultaneous changes occurring in phrenic activity. Three different kinds of discharge patterns were observed: (a) inspiratory, (b) phasic activity during both inspiration and expiration, and (c) continuous random activity with no respiratory modulation. These fibers could be grouped into three categories according to their pattern of discharge during CO2 breathing. Type I fibers, mean conduction velocity of 30.0 m/sec, exhibited only an inspiratory phasic discharge during 100% O2 breathing. Their discharge frequency increased rapidly with higher levels of CO2 and hypoxia. Type II fibers, mean conduction velocity of 36.7 m/sec, had three different kinds of inspiratory-expiratory discharge patterns during 100% O2 breathing. With increasing hypercapnia or hypoxia fibers of this group discharged phasically during inspiration and discharge at low frequency during expiration. Type III fibers had a non phasic discharge pattern at 100% O2 breathing and at all levels of CO2 tested (up to 10%). Discharge frequency rose during CO2 rebreathing and hypoxia, but the rate of increase was much less than Type I and Type II fibers. Their mean conduction velocity was 41.3 m/sec. The inspiratory activity of Type I and II fibers increased their activity more than the phrenic during hypercapnia and hypoxia. Type II and Type III fibers are responsible at least in part for the tonic activity of the nerve.     

Estimation of intrapleural pressure in the newborn

We examined the changes in esophageal (Pes), proximal airway (Paw), and direct intrapleural (Ppl) pressure measurements following end-expiratory airway occlusion in anesthetized spontaneously breathing newborn piglets. Simultaneous occluded pressure measurements were obtained during resting ventilation, inspiratory resistive loaded (IRL) breathing, and bilateral transvenous phrenic nerve stimulation. During spontaneous resting ventilation, occluded Paw/Ppl averaged 104 +/- 4% and occluded Pes/Ppl averaged 89 +/- 3%. Similar values were found for occluded spontaneous breaths with IRL. During phrenic nerve stimulation at end-expiratory lung volume, occluded Paw/Ppl averaged 104 +/- 6% while occluded Pes/Ppl decreased to 70 +/- 22%. We conclude that proximal airway pressure more accurately reflects intrapleural pressure than esophageal pressure with occlusion in newborn swine. During phrenic nerve stimulation, esophageal pressure measures are grossly inaccurate estimates of intrapleural pressure with occlusion.     

Influence of lung volume on respiratory responses to spontaneous bladder contractions

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.     

Selective depression by ethanol of upper airway respiratory motor activity in cats

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.     

Influence of lung volume on phrenic, hypoglossal and mylohyoid nerve activities

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.     

Activities of pulmonary stretch receptors during ventilatory cycles without lung inflation

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.     

Response of the goat carotid body to acute and prolonged hypercapnia

The effect of prolonged hypercapnia on carotid chemoreceptor discharge frequency has not been elucidated. In addition, the effect of acute hypercapnia on chemoreceptor discharge has not been determined in the goat, a species commonly used for ventilatory control studies. Therefore, we determined the effects of acute and prolonged normoxic-hypercapnia on single fiber output of the carotid body of chloralose anesthetized goats. The animals were paralyzed and artificially ventilated. The average acute response curve for 12 single fibers was linear over the range of 30-80 Torr PaCO2 with a mean slope of 0.115 +/- 0.057 (SD) imp.sec-1.Torr-1 PaCO2. Elevated discharge frequency was maintained during prolonged (up to 240 min, n = 11) steady-state hypercapnia (X PaCO2 = 85 Torr). No systematic time-dependent changes in afferent discharge frequency occurred during the period. The findings obtained during sustained hypercapnia are in contrast to the time-dependent increase in carotid body activity seen previously in our laboratory with prolonged normocapnic-hypoxia of up to 240 min duration.     

Discharge of pulmonary rapidly adapting stretch receptors during HFO ventilation.

High-frequency oscillatory ventilation (HFOV) has been shown to stimulate slowly adapting pulmonary stretch receptors (PSR) and thereby to inhibit spontaneous breathing, i.e. HFOV prolongs expiration or even elicits normocapnic apnea. However, during HFOV respiratory effects possibly mediated by pulmonary rapidly adapting receptors (RAR) have also been observed, e.g., diaphragmatic activation or augmented breaths. Therefore, we analyzed HFOV-induced changes in RAR activity in anaesthetized rabbits by mean of single fibre preparations of vagal RAR afferents. HFOV was applied in several combinations of airway pressure (Paw) and oscillation frequency (fOsc). In the sample of 60 RAR fibres prepared in 20 rabbits we found a wide spectrum of discharge patterns during HFOV. The inspiratory discharge rate during HFOV was increased in 38, decreased in 10, and unchanged in 12 RAR. The expiratory discharge rate was increased in 34, decreased in 17, and unchanged in 9 RAR. The effects of gradually changing Paw or of fOsc during HFOV were different in different fibres. In 17 fibres both inspiratory and expiratory discharge rates rose with increasing Paw during HFOV, whereas 19 fibres were not affected by increasing Paw. In some fibres either the inspiratory (12) or the expiratory (9) activity was inhibited in proportion to increasing Paw. From these results we conclude, that (a) the changes of RAR activity during HFOV are heterogeneous and the reflex effects of RAR stimulation may be balanced by RAR with decreased activity; (b) this heterogeneity of RAR discharge patterns explains the dominancy in the control of breathing during HFOV of the homogeneously stimulated PSR; and (c) depending on HFOV ventilatory parameters used the overall RAR stimulation may be strong enough to overrule the inspiration-inhibiting effects of PSR.     

Responses of early and late onset phrenic motoneurons to lung inflation

In anesthetized or decerebrate cats that were paralyzed and ventilated with a cycle-triggered pump, we produced changes in activity of the whole phrenic nerve and of individual phrenic motoneurons (fibers or cells in the spinal cord) by withholding lung inflation during the inspiratory (I) phase. The neurons were classified into early- and late-onset types (discharge onset less or greater than 80 msec, respectively, after whole phrenic onset). Both unit and whole phrenic activity exhibited a variety of responses to inflation (excitation, depression, or no effect); but there were no consistent differences between responses of early- and late-onset neurons. The distribution of responses was quite different from that of dorsal respiratory group (DRG) I neurons (Cohen and Feldman, 1984); in particular there was no group of phrenic neurons corresponding to the late-onset I-beta neurons (I neurons excited by inflation). We conclude that the inputs to late-onset phrenic neurons are not predominantly or exclusively from late-onset DRG neurons.     

The split-respiratory centre in the cat: responses to hypercapnia

In 22 cats anaesthetized with halothane, vagotomised, paralyzed with d-tubocurarine and artificially ventilated, the medulla was split in the midline and the response of phrenic motoneurones, efferent vagus nerve and medullary respiratory neurones to hypercapnia was studied. In 18 successful experiments the mid-sagittal incision abolished all electrical activities but an inhalation of a 5% CO2-oxygen mixture promptly restored rhythmic firing in both the medullary units and efferent nerves when PaCO2 reached 55 mm Hg on the average (mean pH = 7.20). Switching the ventilation back to normocapnia was followed by a gradual disappearance of the activities usually when PaCO2 and pH returned to control values. We conclude that splitting the brainstem in cat affects the respiratory rhythmogenesis, presumably by increasing the CO2-threshold of medullary respiratory neurones.     

Effect of hypoxic, hyperoxic or hypercapnic ventilation on inspiratory termination in the cat

Intercostal nerve stimulation was used to examine the effects of altered concentrations of inspired oxygen or carbon dioxide on the termination of inspiration. Experiments were performed in decerebrate cats which were paralyzed, artificially ventilated and bilaterally vagotomized. The threshold current at which electrical stimulation of the T6 intercostal nerve terminated phrenic neural activity was determined at 10 different delays from the onset of phrenic nerve discharge. Ventilation with either hypercapnic normoxic gas (4% CO2) or hypoxic gas (17% O2) increased the threshold current required for inspiratory termination. Hyperoxic ventilation (45% O2), however, decreased the threshold for inspiratory termination. Bilateral section of the carotid sinus nerve abolished the response to hyperoxic ventilation, but did not alter the response to normoxic hypercapnia. These results demonstrate that an oxygen-related stimulus transduced by the peripheral chemoreceptors can influence the mechanism(s) responsible for inspiratory termination.