Role of the carotid chemoreceptors in regulation of inspiratory onset

We studied the effect of intermittent tidal breaths of CO2-enriched air (3-9% CO2) on the duration of expiratory time (TE) in five trained dogs, before and after (3 dogs) bilateral surgical denervation of the carotid bodies (CBD). During studies the dogs lay quietly, either awake or in nonrapid-eye-movement sleep, and breathed through a cuffed endotracheal tube inserted via a chronic tracheostomy. Studies were conducted during bilateral blockade of the cervical vagus nerves (VB), achieved by circulating cold alcohol through radiators placed around exteriorized vagal skin loops. Prior to CBD, single breaths of CO2 significantly shortened TE and thus advanced the onset of the subsequent inspiration. Further, the decrease in TE induced by the CO2 stimulus was in direct proportion to the inspired CO2 concentration. Thus 3% CO2 shortened TE by 1.82 +/- 0.93 (SD) s, and 9% CO2 by 3.44 +/- 1.53 s. Changes in TE occurred in the absence of associated changes in either tidal volume or inspiratory time. After CBD, test breaths of CO2 failed to shorten TE during VB. We conclude that the carotid bodies have the ability to mediate changes in the timing of inspiratory onset in response to a transient CO2 stimulus.     

Expiratory flow pattern and respiratory mechanics

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

Ventilation is unstable during drowsiness before sleep onset.

Ventilation is unstable during drowsiness before sleep onset. We have studied the effects of transitory changes in cerebral state during drowsiness on breath duration and lung volume in eight healthy subjects in the absence of changes in airway resistance and fluctuations of ventilation and CO2 tension, characteristic of the onset of non-rapid eye movement sleep. A volume-cycled ventilator in the assist control mode was used to maintain CO2 tension close to that when awake. Changes in cerebral state were determined by the EEG on a breath-by-breath basis and classified as alpha or theta breaths. Breath duration and the pause in gas flow between the end of expiratory airflow and the next breath were computed for two alpha breaths which preceded a theta breath and for the theta breath itself. The group mean (SD) results for this alpha-to-theta transition was associated with a prolongation in breath duration from 5.2 (SD 1.3) to 13.0 s (SD 2.1) and expiratory pause from 0.7 (SD 0.4) to 7.5 s (SD 2.2). Because the changes in arterial CO2 tension (PaCO2) are unknown during the theta breaths, we made in two subjects a continuous record of PaCO2 in the radial artery. PaCO2 remained constant from the alpha breaths through to the expiratory period of the theta breath by which time the duration of breath was already prolonged, representing an immediate and altered ventilatory response to the prevailing PaCO2. In the eight subjects, the CO2 tension awake was 39.6 Torr (SD 2.3) and on assisted ventilation 38.0 Torr (1.4). We conclude that the ventilatory instability recorded in the present experiments is due to the apneic threshold for CO2 being at or just below that when awake.     

Interaction between upper airway negative pressure pulses and CO2 on breathing pattern

The interaction between CO2 and negative pressure pulses on breathing pattern was investigated in 10 anesthetized, spontaneously breathing rabbits. The upper airway was functionally isolated into a closed system. A servo-respirator triggered by the inspiratory activity of the diaphragm was used to apply pressure pulses of -15 cmH2O to the isolated upper airway in early inspiration while the animal was breathing room air, 100% O2, 6% CO2 in O2, or 9% CO2 in O2. The negative pressure pulses produced a reversible inhibition of inspiration in most trials with resultant increase in inspiratory duration (TI); no change was observed in peak diaphragmatic electromyogram (Dia EMG) or expiratory duration, whereas a decrease was seen in mean inspiratory drive (peak Dia EMG/TI). This prolongation of inspiratory duration and decrease in mean inspiratory drive with negative pressure pulses persisted at higher levels of CO2; the slopes of the test breaths were not significantly different from that of control breaths. These results suggest that upper airway negative pressure pulses are equally effective in altering the breathing pattern at all levels of CO2.     

Effects of inspiratory resistive load on respiratory control in hypercapnia and exercise

Eight healthy young men underwent two separate steady-state incremental exercise runs within the aerobic range on a treadmill with alternating periods of breathing with no load (NL) and with an inspiratory resistive load (IRL) of approximately 12 cmH2O.1-1.s. End-tidal PCO2 was maintained constant throughout each run at the eucapnic or a constant hypercapnic level by adding 0-5% CO2 to the inspired O2. Hypercapnia caused a steepening, as well as upward shift, relative to the corresponding eucapnic ventilation-CO2 output (VE - VCO2) relationship in NL and IRL. Compared with NL, the VE - VCO2 slope was depressed by IRL, more so in hypercapnic [-19.0 +/- 3.4 (SE) %] than in eucapnic exercise (-6.0 +/- 2.0%), despite a similar increase in the slope of the occlusion pressure at 100 ms - VCO2 (P100 - VCO2) relationship under both conditions. The steady-state hypercapnic ventilatory response at rest was markedly depressed by IRL (-22.6 +/- 7.5%), with little increase in P100 response. For a given inspiratory load, breathing pattern responses to separate or combined hypercapnia and exercise were similar. During IRL, VE was achieved by a greater tidal volume (VT) and inspiratory duty cycle (TI/TT) along with a lower mean inspiratory flow (VT/TI). The increase in TI/TT was solely because of a prolongation of inspiratory time (TI) with little change in expiratory duration for any given VT. The ventilatory and breathing pattern responses to IRL during CO2 inhalation and exercise are in favor of conservation of respiratory work.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of hypercapnia on Breuer-Hering threshold for inspiratory termination

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

Effect of ketamine on control of breathing in cats

We studied minute ventilation, breathing pattern, end-tidal CO2 partial pressure (PACO2), and tracheal occlusion pressure in cats anesthetized with ketamine (40 and 80 mg/kg) before and after CO2 inhalation. Before CO2 administration ventilation was reduced and PACO2 increased relative to unanesthetized cats at both ketamine doses. Breathing pattern was of the "apneustic" type, being characterized by 1) prolonged inspiratory duration and relatively short expiratory time and 2) markedly curvilinear (convex upward) inspiratory volume-time profile. The latter reflected a similar curvilinearity in the tracheal occlusion pressure waveform. During CO2 inhalation, the ventilatory response to CO2 was similar to that in unanesthetized cats in spite of a depressed tracheal occlusion pressure response. This discrepancy was due to the fact that in the presence of a convex upward inspiratory volume-time profile, the shortening of inspiratory duration with increasing CO2 results in a marked increase of mean inspiratory flow, and hence the ventilatory response to CO2 remains high.     

Influence of airway resistance on hypoxia-induced periodic breathing.

We studied the effects of changing upper airway pressure on the variability of the dynamic response of ventilation to a hypoxic disturbance in 11 spontaneously breathing dogs. Supralaryngeal pressure, instantaneous inspiratory flow, end-expiratory lung volume, and the inspiratory and expiratory O2 and CO2 concentrations were continuously recorded at baseline and after a 1.5-min hypoxic stimulus (abrupt normoxic recovery). Arterial blood gases were obtained at baseline, at the end of the hypoxic period, and after 1 min of recovery. Airway resistances were modified during the recovery by changing the composition of the inspired gas (all with an inspiratory O2 fraction of 20.9%) among four different trials: two trials were realized with air (density 1.12 g/l), and the other two were with He or SF6 (respective density 0.42 and 4.20) in random order. There was no difference between baseline minute ventilation, arterial blood gases, and supralaryngeal resistance values preceding the trials. The hypoxemic and hypocapnic levels and the hypoxia-induced hyperventilation reached during the hypoxic tests were identical for the different hypoxic stimuli. The supralaryngeal resistance measured at peak flow was dramatically influenced by the composition of the inspired gas: 8.8 +/- 1.8 and 6.9 +/- 1.7 (SE) cmH2O.l-1.s with air, 7.2 +/- 2.2 with He, 21.9 +/- 5.5 with SF6 (P less than 0.05). Ventilatory fluctuations were consistently seen during the posthypoxic period. They were characterized by a strength index value (M) (Waggener et al. J. Appl. Physiol. 56: 576-581, 1984).(ABSTRACT TRUNCATED AT 250 WORDS)     

Inspiratory-to-expiratory time ratio and alveolar ventilation during high-frequency ventilation in dogs

It has been suggested that the increase in inspiratory flow rate caused by a decrease in the inspiratory-to-expiratory time ratio (I:E) at a constant tidal volume (VT) could increase the efficiency of ventilation in high-frequency ventilation (HFV). To test this hypothesis, we studied the effect of changing I:E from 1:1 to 1:4 on steady-state alveolar ventilation (VA) at a given VT and frequency (f) and at a constant mean lung volume (VL). In nine anesthetized, paralyzed, supine dogs, HFV was performed at 3, 6, and 9 Hz with a ventilator that delivered constant inspiratory and expiratory flow rates. Mean airway pressure was adjusted so that VL was maintained at a level equivalent to that of resting FRC. At each f and one of the I:E chosen at random, VT was adjusted to obtain a eucapnic steady state [arterial pressure of CO2 (PaCO2) = 37 +/- 3 Torr]. After 10 min of each HFV, PaCO2, arterial pressure of O2 (PaO2), and CO2 production (VCO2) were measured, and I:E was changed before repeating the run with the same f and VT. VA was calculated from the ratio of VCO2 and PaCO2. We found that the change of I:E from 1:1 to 1:4 had no significant effects on PaCO2, PaO2, and VA at any of the frequencies studied. We conclude, therefore, that the mechanism or mechanisms responsible for gas transport during HFV must be insensitive to the changes in inspiratory and expiratory flow rates over the VT-f range covered in our experiments.     

Mechanism of action of ozone on the human lung

Fourteen healthy normal volunteers were randomly exposed to air and 0.5 ppm of ozone (O3) in a controlled exposure chamber for a 2-h period during which 15 min of treadmill exercise sufficient to produce a ventilation of approximately 40 l/min was alternated with 15-min rest periods. Before testing an esophageal balloon was inserted, and lung volumes, flow rates, maximal inspiratory (at residual volume and functional residual capacity) and expiratory (at total lung capacity and functional residual capacity) mouth pressures, and pulmonary mechanics (static and dynamic compliance and airway resistance) were measured before and immediately after the exposure period. After the postexposure measurements had been completed, the subjects inhaled an aerosol of 20% lidocaine until response to citric acid aerosol inhalation was abolished. All of the measurements were immediately repeated. We found that the O3 exposure 1) induced a significant mean decrement of 17.8% in vital capacity (this change was the result of a marked fall in inspiratory capacity without significant increase in residual volume), 2) significantly increased mean airway resistance and specific airway resistance but did not change dynamic or static pulmonary compliance or viscous or elastic work, 3) significantly reduced maximal transpulmonary pressure (by 19%) but produced no changes in inspiratory or expiratory maximal mouth pressures, and 4) significantly increased respiratory rate (in 5 subjects by more than 6 breaths/min) and decreased tidal volume.(ABSTRACT TRUNCATED AT 250 WORDS)     

Breathing pattern and CO2 response in newborn rats before and during anesthesia

We have studied the breathing pattern (minute ventilation VE, tidal volume VT, and respiratory rate f) in newborn rats before and during barbiturate (20-30 mg/kg ip) or ketamine anesthesia (40-80 mg/kg ip). Animals were intact and prone in a flow plethysmograph in thermoneutral conditions. Before anesthesia, CO2 breathing (5 min in 5% and 5 min in 10% CO2 in O2) resulted in a substantial increase in VE (169 and 208%, respectively), which was maintained throughout the entire CO2 breathing period. This indicates that, despite the extremely large VE per kilogram at rest, in these small animals there is still a large reserve for a sustained increase in VE. During barbiturate, the resting VE dropped to 45% of control, due to a reduction in VT (83%) and f (59%). This latter result was due to a prolongation of the expiratory time (214%) with no significant changes in inspiratory time. CO2 response was also much depressed, to approximately 63% of the control. The late portion of the expiratory flow-volume curves, the slope of which represents the expiratory time constant of the system, was similar before and during anesthesia in approximately 50% of the animals, whereas it increased during anesthesia in the remaining animals. Although compliance of the respiratory system was generally unaltered, the increased impedance during anesthesia probably reflected an increased resistance. Qualitatively similar results were obtained during ketamine anesthesia. Therefore, as observed in adult mammals, anesthesia in newborn rats has a marked depressant effect on resting breathing pattern and CO2 response, occasionally accompanied by an increase in the expiratory impedance of the respiratory system.     

Airway anesthesia effects on hypercapnic breathing pattern in humans

Minute ventilation (VE) and breathing pattern during an abrupt increase in fractional CO2 were compared in 10 normal subjects before and after airway anesthesia. Subjects breathed 7% CO2-93% O2 for 5 min before and after inhaling aerosolized lidocaine. As a result of airway anesthesia, VE and tidal volume (VT) were greater during hypercapnia, but there was no effect on inspiratory time (TI). Therefore, airway anesthesia produced an increase in mean inspiratory flow (VT/TI) during hypercapnia. The increase in VT/TI was compatible with an increase in neuromuscular output. There was no effect of airway anesthesia on the inspiratory timing ratio or the shape and position of the curve relating VT and TI. We also compared airway resistance (Raw), thoracic gas volume, forced vital capacity, forced expired volume at 1s, and maximum midexpiratory flow rate before and after airway anesthesia. A small (0.18 cmH2O X l-1 X s) decrease in Raw occurred after airway anesthesia that did not correlate with the effect of airway anesthesia on VT/TI. We conclude that airway receptors accessible to airway anesthesia play a role in hypercapnic VE.     

Significance of airway resistance for the pattern of breathing and lung volumes in exercising humans

The effects of increased airway resistance on lung volumes and pattern of breathing were studied in eight subjects performing leg exercise on a cycle ergometer. Airway resistance was changed 1) by increasing the density (D) of the respired gas by a factor of 4.2 and changing the inspired gas from O2 at 1.3 bar to air at 6 bar and 2) by increasing airway flow rates by exposing the subjects to incremental work loads of 0-200 W. Increased gas D caused a slower and deeper respiration at rest and during exercise and, at work loads greater than 120 W, depressed the responses of ventilation and mean inspiratory flow. Raised airway resistance induced by increases in D and/or airway flow rates altered respiratory timing by increasing the ratio of inspiratory time (TI) to total breath duration. Furthermore, analyses of the relationships between tidal volume and TI and between end-inspiratory volume and TI revealed elevation of Hering-Breuer inspiratory volume thresholds. We propose that this elevation, and hence exercise-induced increases of tidal volume, can largely be explained by previous observations that the threshold of the inspiratory off-switch mechanisms depends on central inspiratory activity (cf. C. von Euler, J. Appl. Physiol. 55: 1647-1659, 1983), which in turn increases with airway resistance (Acta Physiol. Scand. 120: 557-565, 1984).     

Blood flow in respiratory muscles during maximal exertion in ponies with laryngeal hemiplegia

The interactive effects of upper airway negative pressure and hypercapnia on the pattern of breathing were assessed in pentobarbital-anesthetized cats. At any given level of pressure in the upper airway, hypercapnia increased respiratory rate, reduced inspiratory time, and augmented tidal volume, inspiratory airflow, and the peak and rate of rise of diaphragm electrical activity. Conversely, at any given level of CO2, upper airway negative pressure decreased respiratory rate, prolonged inspiratory time, and depressed inspiratory airflow and diaphragm electromyogram (EMG) rate of rise. Application of negative pressure to the upper airway shifted the relationship between tidal volume and inspiratory time upward and rightward. The relationship between inspiratory and expiratory times, however, was linearly correlated over a wide range of chemical drives and levels of upper airway pressure. These results suggest that in the anesthetized cat upper airway negative pressure afferent inputs 1) interact in an additive fashion with hypercapnia to alter the pattern of breathing, 2) interact multiplicatively with CO2 to influence mean inspiratory airflow and diaphragm EMG rate of rise, 3) depress the generation of central inspiratory activity, 4) increase the time-dependent volume threshold for inspiratory termination, and 5) affect the ratio between inspiratory and expiratory times in a similar manner as alterations in PCO2.     

Separation of factors responsible for change in breathing pattern induced by instrumentation

Employment of mouthpiece and noseclips (MP + NC) has repeatedly been shown to increase tidal volume (VT), but its effect on respiratory frequency (f) and its subsets is controversial. The mechanisms accounting for this alteration in breathing pattern are poorly understood and may include stimulation of oral or nasal sensory receptors or alteration in the route of breathing. In this study we demonstrated that use of a MP + NC, compared with nonobtrusive measurement with a calibrated respiratory inductive plethysmograph, alters the majority of the volume and time indexes of breathing pattern, with increases in minute ventilation (P less than 0.01), VT (P less than 0.001), inspiratory time (TI, P less than 0.05), expiratory time (TE, P less than 0.05), mean inspiratory flow (P less than 0.05), and mean expiratory flow (P less than 0.05) and a decrease in f(P less than 0.05). Separating the potential mechanisms we found that when the respiratory route was not altered, independent oral stimulation (using an occluded MP) or nasal stimulation (by applying paper clips to the alae nasi) did not change the breathing pattern. In contrast, obligatory oral breathing without additional stimulation of the oral or nasal sensory receptors caused increases in VT (P less than 0.05), TI (P less than 0.05), and TE (P less than 0.01) and a fall in f(P less than 0.05). Heating and humidifying the inspired air did not prevent the alteration in breathing pattern with a MP. Thus change in the respiratory route is the major determinant of the alteration in breathing pattern with a MP + NC.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pseudorandom testing of ventilatory response to inspired carbon dioxide in man

A new method of testing the transient ventilatory response to inspired CO2 in humans has been developed in an attempt to improve the resolution and reproducibility of measures of peripheral chemoreceptor-mediated dynamics. The test input consisted of varying the level of inspired CO2 between 0 and 6-8% on a pseudorandom breath-by-breath basis. Cross-correlating this input with responses of end-tidal CO2, tidal volume, durations of inspiration and expiration, and respiratory rate yielded estimates of impulse responses. Computer simulation results and data collected in two subjects showed that reliable estimates of circulatory time lags and rapid dynamics are possible with this method. In one subject, the response dynamics observed were consistent with peripheral chemoreceptor rate sensitivity or adaptation. The rapid changes in inspiratory and expiratory durations also observed are probably mediated by peripheral chemoreceptors and appear to depend on the phase of the breathing cycle at which the CO2 stimulus arrives.     

Fatigue of the inspiratory muscle pump in humans: an isoflow approach

A new method is described for measurement of inspiratory muscle endurance in humans that is based on isokinetic principles of muscle testing (i.e., measurement of maximum force during a constant velocity of shortening). Subjects inspired maximally while their lungs were inflated at a constant rate during each breath for 10 min. Inspiratory and expiratory time, flow rate, tidal volume, and end-tidal CO2 were maintained constant. In each subject, maximum inspiratory mouth pressure exponentially decayed over the first few minutes to an apparent sustainable value. Repeated tests in experienced subjects showed high reproducibility of sustainable pressure measurements. To determine the effects of flow, endurance tests were repeated in four subjects at flows of 0.75, 1.0, and 1.25 l/s, with a constant duty cycle. As flow increased, the maximum pressures that could be attained at rest and the maximum sustainable pressures decreased. At each flow, the sustainable pressure remained a constant fraction of the maximum pressure attainable at rest. We interpret the decay in mouth pressure during isoflow endurance tests to directly reflect the loss of net inspiratory muscle force available by maximum voluntary activation of the inspiratory pump.     

Effects of hypercapnia on inspiratory and expiratory muscle activity during expiration

Persistence of inspiratory muscle activity during the early phase of expiratory airflow slows the rate of lung deflation, whereas heightened expiratory muscle activity produces the opposite effect. To examine the influence of increased chemoreceptor drive and the role of vagal afferent activity on these processes, the effects of progressive hypercapnia were evaluated in 12 anesthetized tracheotomized dogs before and after vagotomy. Postinspiratory activity of inspiratory muscles (PIIA) and the activity of expiratory muscles were studied. During resting breathing, the duration of PIIA correlated with the duration of inspiration but not with expiration. Parasternal intercostal PIIA was directly related to that of the diaphragm. Based on their PIIA, dogs could be divided into two groups: one with prolonged PIIA (mean 0.57 s) and the other with brief PIIA (mean 0.16 s). Hypercapnia caused progressive shortening of the PIIA in the dogs with prolonged PIIA during resting breathing. The electrical activity of the external oblique and internal intercostal muscles increased gradually during CO2 rebreathing in all dogs both pre- and postvagotomy. After vagotomy, abdominal activity continued to increase with hypercapnia but was less at all levels of PCO2. The internal intercostal response to hypercapnia was not affected by vagotomy. The combination of shorter PIIA and augmented expiratory activity with hypercapnia might, in addition to changes in lung recoil pressure and airway resistance, hasten exhalation.     

Velocity of shortening of inspiratory muscles and inspiratory flow

Respiratory muscle length was measured with sonomicrometry to determine the relation between inspiratory flow and velocity of shortening of the external intercostal and diaphragm. Electromyographic (EMG) activity and tidal shortening of the costal and crural segments of the diaphragm and of the external intercostal were recorded during hyperoxic CO2 rebreathing in 12 anesthetized dogs. We observed a linear increase of EMG activity and peak tidal shortening of costal and crural diaphragm with alveolar CO2 partial pressure. For the external intercostal, no consistent pattern was found either in EMG activity or in tidal shortening. Mean inspiratory flow was linearly related to mean velocity of shortening of costal and crural diaphragm, with no difference between the two segments. Considerable shortening occurred in costal and crural diaphragm during inspiratory efforts against occlusion. We conclude that the relation between mean inspiratory flow and mean velocity of shortening of costal and crural diaphragm is linear and can be altered by an inspiratory load. There does not appear to be a relationship between inspiratory flow and velocity of shortening of external intercostals.     

Respiratory responses in reversible diaphragm paralysis

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