Alterations in respiratory muscle activation in the ischemic fatigued canine diaphragm

The purpose of the present study was to examine the respiratory motor response to diaphragm fatigue. Studies were performed using in situ diaphragm muscle strips dissected from the left costal diaphragm in anesthetized dogs. The left inferior phrenic artery was isolated, and diaphragmatic strip fatigue was elicited by occluding this vessel. Strip tension, strip electromyographic activity, parasternal electromyographic activity, and the electromyogram of the right hemidiaphragm were recorded during spontaneous breathing efforts before, during, and after periods of phrenic arterial occlusion. In separate trials, we examined the neuromuscular responses to phrenic arterial occlusion at arterial PCO2 (PaCO2) of 40, 55, and 75 Torr. No fatigue and no alteration in electromyographic activities were observed in trials at PaCO2 of 40 Torr. During trials at PaCO2 of 55 and 75 Torr, however, diaphragm tension fell, the peak height of the diaphragm strip electromyogram decreased, and the peak heights of the parasternal and right hemidiaphragm electromyograms increased. Relief of phrenic arterial occlusion resulted in a return of strip tension and all electromyograms toward base-line values. In additional experiments, the left phrenic nerve was sectioned in the chest after producing fatigue. Phrenic section was followed by an increase in the peak height of the left phrenic neurogram (recorded above the site of section). This latter finding suggests that diaphragm strip motor drive may be reflexly inhibited during the development of fatigue by neural traffic carried along phrenic afferents.     

Phrenic neural output during hypoxia in dogs: constant-flow ventilation vs. spontaneous breathing.

We studied the effects of removing cyclic pulmonary afferent neural information on respiratory pattern generation in anesthetized dogs. Phrenic neural output during spontaneous breathing (SB) was compared with that occurring during constant-flow ventilation (CFV) at several levels of eucapnic hypoxemia. Hypoxia caused an increase in both the frequency and the amplitude of the moving time average (MTA) phrenic neurogram during both SB and CFV. The change in frequency as arterial saturation was reduced from 90 to 60% during SB was significantly higher than that during CFV [SB, 32.3 +/- 10.9 (SD) breaths/min; CFV, 10.3 +/- 5.8 breaths/min; P = 0.001]. By contrast, the increase in the amplitude of the MTA phrenic neurogram was smaller (SB, 0.62 +/- 0.68 units; CFV, 1.35 +/- 0.81 units; P = 0.01). The changes in frequency with hypoxia during both modes of ventilation resulted primarily from a shortening of expiratory time. Both inspiratory time and expiratory time were greater during CFV than during SB, but their change in response to hypoxia was not significantly different. We conclude that the amplitude response of the MTA phrenic neurogram to hypoxia is similar to that seen during hypercapnia; in the presence of phasic afferent feedback the MTA amplitude response is decreased and the frequency response is increased relative to the response observed in the absence of phasic afferents.     

Synchronization of respiratory frequency by somatic afferent stimulation.

In cats anesthetized with chloralose-urethan, vagotomized, paralyzed, and artifically ventilated, superficial radial (cutaneous) and hamstring (muscle) nerve afferents were stimulated while phrenic nerve electrical activity was recorded. The results obtained with both types of nerves were similar. Stimulation in mid and late expiration advanced the onset of the next inspiration, shortening its duration. Stimulation in early inspiration advanced, while that in late inspiration delayed, the onset of the next expiration. These effects were often accompanied by changes in phrenic motoneuron firing patterns (earlier recruitment, increased discharge frequency, increased slope of integrated phrenic neurogram). Repetitive somatic afferent stimulation produced sustained increases in respiratory frequency in all cats and in half of them entrainment of respiratory frequency to the frequency of stimulation occurred at ratios such as 4:3, 4:5, 1:2, 1:3, 1:4, and 1:7. The lowest stimulus intensity required for evoking these phase shifts was between 5 and 10T (threshold of most excitable fibers) for muscle afferents and between 1 and 2T for cutaneous afferents. These results demonstrate the existence of a reflex mechanism capable of locking respiratory frequency to that of a periodic somatic afferent input. They also provide an experimental basis for the hypothesis that reflexes are resposible for the observed locking between step or pedal frequency and respiratory rate during exercise in man.     

Excitation of dorsal and ventral respiratory group neurons by phrenic nerve afferents

The projections of phrenic nerve afferents to neurons in the dorsal (DRG) and ventral (VRG) respiratory group were studied in anesthetized, paralyzed, and vagotomized cats. Extracellular recordings of neuronal responses to vagal nerve and cervical phrenic nerve stimulation (CPNS) indicated that about one-fourth of the DRG respiratory-modulated neurons were excited by phrenic nerve afferents with an onset latency of approximately 20 ms. In addition, non-respiratory-modulated neurons within the DRG were recruited by CPNS. Although some convergence of vagal and phrenic afferent input was observed, most neurons were affected by only one type of afferent. In contrast to the DRG, only 3 out of 28 VRG respiratory-modulated neurons responded to CPNS. A second study determined that most of these neuronal responses were due to activation of diaphragmatic afferents since 90% of the DRG units activated by CPNS were also excited at a longer latency by thoracic phrenic nerve stimulation. The difference in onset latency of neuronal excitation indicates an afferent peripheral conduction velocity of about 10 m/s, which suggests that they are predominately small myelinated fibers (group III) making paucisynaptic connections with DRG neurons. Decerebration, decerebellation, and bilateral transection of the dorsal columns at C2 do not abolish the neuronal responses to cervical PNS.     

Effects of diaphragmatic ischemia on the inspiratory motor drive.

To assess the effect of diaphragmatic ischemia on the inspiratory motor drive, we studied the in situ isolated and innervated left diaphragm in anesthetized, vagotomized, and mechanically ventilated dogs. The arterial and venous vessels of the left diaphragm were catheterized and isolated from the systemic circulation. Inspiratory muscle activation was assessed by recording the integrated electromyographic (EMG) activity of the left and right costal diaphragms and parasternal intercostal and alae nasi muscles. Tension generated by the left diaphragm during spontaneous breathing attempts was also measured. In eight animals, left diaphragmatic ischemia was induced by occluding the phrenic artery for 20 min, followed by 10 min of reperfusion. This elicited a progressive increase in EMG activity of the left and right diaphragms and parasternal and alae nasi muscles to 170, 157, 152, and 128% of baseline values, respectively, an increase in the frequency of breathing efforts, and no change in left diaphragmatic spontaneous tension. Thus the ratio of left diaphragmatic EMG to tension rose progressively during ischemia. During reperfusion, only the frequency of breathing efforts and alae nasi EMG recovered completely. In four additional animals, left diaphragmatic ischemia was induced after the left phrenic nerve was sectioned. Neither EMG activity of inspiratory muscles nor respiratory timing changed significantly during ischemia. In conclusion, diaphragmatic ischemia increases inspiratory motor drive through activation of phrenic afferents. The changes in alae nasi activity and respiratory timing indicate that this influence is achieved through supraspinal pathways.     

Attenuation of phrenic motor discharge by phrenic nerve afferents

Short latency phrenic motor responses to phrenic nerve stimulation were studied in anesthetized, paralyzed cats. Electrical stimulation (0.2 ms, 0.01-10 mA, 2 Hz) of the right C5 phrenic rootlet during inspiration consistently elicited a transient reduction in the phrenic motor discharge. This attenuation occurred bilaterally with an onset latency of 8-12 ms and a duration of 8-30 ms. Section of the ipsilateral C4-C6 dorsal roots abolished the response to stimulation, thereby confirming the involvement of phrenic nerve afferent activity. Stimulation of the left C5 phrenic rootlet or the right thoracic phrenic nerve usually elicited similar inhibitory responses. The difference in onset latency of responses to cervical vs. thoracic phrenic nerve stimulation indicates activation of group III afferents with a peripheral conduction velocity of approximately 10 m/s. A much shorter latency response (5 ms) was evoked ipsilaterally by thoracic phrenic nerve stimulation. Section of either the C5 or C6 dorsal root altered the ipsilateral response so that it resembled the longer latency contralateral response. The low-stimulus threshold and short latency for the ipsilateral response to thoracic phrenic nerve stimulation suggest that it involves larger diameter fibers. Decerebration, decerebellation, and transection of the dorsal columns at C2 do not abolish the inhibitory phrenic-to-phrenic reflex.     

A comparison of central aspects of fatigue in submaximal and maximal voluntary contractions.

Magnetic and electrical stimulation at different levels of the neuraxis show that supraspinal and spinal factors limit force production in maximal isometric efforts ("central fatigue"). In sustained maximal contractions, motoneurons become less responsive to synaptic input and descending drive becomes suboptimal. Exercise-induced activity in group III and IV muscle afferents acts supraspinally to limit motor cortical output but does not alter motor cortical responses to transcranial magnetic stimulation. "Central" and "peripheral" fatigue develop more slowly during submaximal exercise. In sustained submaximal contractions, central fatigue occurs in brief maximal efforts even with a weak ongoing contraction (<15% maximum). The presence of central fatigue when much of the available motor pathway is not engaged suggests that afferent inputs contribute to reduce voluntary activation. Small-diameter muscle afferents are likely to be activated by local activity even in sustained weak contractions. During such contractions, it is difficult to measure central fatigue, which is best demonstrated in maximal efforts. To show central fatigue in submaximal contractions, changes in motor unit firing and force output need to be characterized simultaneously. Increasing central drive recruits new motor units, but the way this occurs is likely to depend on properties of the motoneurons and the inputs they receive in the task. It is unclear whether such factors impair force production for a set level of descending drive and thus represent central fatigue. The best indication that central fatigue is important during submaximal tasks is the disproportionate increase in subjects' perceived effort when maintaining a low target force.     

Bilateral phrenic stimulation: a simple technique to assess diaphragmatic fatigue in humans

Transdiaphragmatic pressure (Pdi) and the rate of relaxation of the diaphragm (tau) were measured at functional residual capacity (FRC) in six normal seated subjects during single-twitch stimulation of both phrenic nerves. The latter were stimulated supramaximally with needle electrodes with square-wave impulses of 0.1-ms duration at 1 Hz before and after diaphragmatic fatigue produced by resistive loaded breathing. Constancy of chest wall configuration was achieved by monitoring the diameter of the abdomen and the rib cage with a respiratory inductive plethysmograph system. During control the peak Pdi generated during the phrenic stimulation amounted to 34.4 +/- 4.2 (SE) cmH2O and represented in each subject a fixed fraction (17%) of its maximal transdiaphragmatic pressure. After diaphragmatic fatigue the peak Pdi decreased by an average of 45%, amounting to 18.1 +/- 2.7 cmH2O 5 min after the fatigue run, and tau increased from 55.2 +/- 9 ms during control to 77 +/- 8 ms 5 min after the fatigue run. The decrease in peak Pdi and the increase in tau observed after the fatigue run persisted throughout the 30 min of the recovery period studied, the peak Pdi amounting to 18.4 +/- 2.8 and 18.9 +/- 3.3 cmH2O and tau to 81.3 +/- 5.7 and 88.7 +/- 10 ms at 15 and 30 min after the end of the fatigue run, respectively. It is concluded that diaphragmatic fatigue can be detected in man by bilateral phrenic stimulation with needle electrodes without any discomfort for the subject and that the decrease in diaphragmatic strength after fatigue is long lasting.     

Influence of phasic afferent information on phrenic neural output during hypercapnia

We measured the moving time average (MTA) of the phrenic neurogram before and after removal of phasic afferent information from the lungs, chest wall, and oscillations in blood gases by using constant-flow ventilation (CFV). Anesthetized dogs were studied at various levels of steady-state and progressive hypercapnia during spontaneous breathing and during CFV. When steady-state and progressive hypercapnia were compared, the frequency and height of the MTA phrenic neurogram were independent of the rate of induction of hypercapnia during each mode of ventilation. During spontaneous ventilation, the response to hypercapnia comprised mainly an increase in frequency with only a slight increase in the amplitude of the MTA phrenic waveform. During muscular paralysis and CFV, the responses were similar to those observed after vagotomy with mainly an increase in the amplitude and only a small increase in frequency. For both spontaneous breathing and CFV, increases in frequency were achieved mainly by a shortening in expiratory time with the inspiratory time remaining relatively constant. Our data support the concept of a centrally patterned respiratory generator, whose inherent pattern is modified by phasic feedback from peripheral receptors mainly of vagal origin.     

Transient respiratory augmentation elicited by acute head-down tilt in the anesthetized cat

Acute head-downtilt (AHDT, 30°) in humans induces a transient ventilatoryaugmentation for 1-2 min accompanied by a high venous return.However, the mechanisms underlying this respiratory response remainobscure because of limitations of experiments carried out in humansubjects. The present study was undertaken to determine whetherAHDT-induced respiratory augmentation exists in the anesthetized,paralyzed, and ventilated cat and, if so, whether this response dependson 1) the cerebellum,2) the carotid sinus (CS)and/or vagal afferents, and3) elevation of central venousreturn. The integrated phrenic neurogram, arterial blood pressure,central venous pressure (CVP), and end-tidalPCO₂ were recorded before, during,and after AHDT. The results showed that AHDT produced a transient (~2min) enhancement of minute phrenic activity (~30%) primarily via anincrease in peak integrated phrenic neurogram amplitude associated witha remarkable elevation of CVP (~3 min). Cerebellectomy, CSdenervation, bilateral vagotomy, or clamping CVP did not affect thepresence of the AHDT-induced minute phrenic activity response. Thesefindings demonstrate that the anesthetized cat is a suitable model forinvestigating the mechanisms involved in AHDT-induced respiratoryaugmentation. Preliminary studies suggest that this response does notrequire the cerebellum, CS/vagal afferents, or an associated rise incentral venous return.

     

Respiratory response to partial paralysis in anesthetized dogs

The ability to maintain alveolar ventilation is compromised by respiratory muscle weakness. To examine the independent role of reflexly mediated neural mechanisms to decreases in the strength of contraction of respiratory muscles, we studied the effects of partial paralysis on the level and pattern of phrenic motor activity in 22 anesthetized spontaneously breathing dogs. Graded weakness induced with succinylcholine decreased tidal volume and prolonged both inspiratory and expiratory time causing hypoventilation and hypercapnia. Phrenic peak activity as well as the rate of rise of the integrated phrenic neurogram increased. However, when studied under isocapnic conditions, increases in the severity of paralysis, as assessed from the ratio of peak diaphragm electromyogram to peak phrenic activity, produced progressive increases in inspiratory time and phrenic peak activity but did not affect its rate of rise. After vagotomy, partial paralysis induced in 11 dogs with succinylcholine also prolonged the inspiratory burst of phrenic activity, indicating that vagal reflexes were not solely responsible for the alterations in respiratory timing. Muscle paresis was also induced with gallamine or dantrolene, causing similar responses of phrenic activity and respiratory timing. Thus, at constant levels of arterial CO2 in anesthetized dogs, respiratory muscle partial paralysis results in a decrease in breathing rate without changing the rate of rise of respiratory motor activity. This is not dependent solely on vagally mediated reflexes and occurs regardless of the pharmacological agent used. These observations in the anesthetized state are qualitatively different from the response to respiratory muscle paralysis or weakness observed in awake subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Adaptation to reflex effects of prolonged lung inflation

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

Superior laryngeal and hypoglossal afferents tonically influence upper airway motor excitability in anesthetized rats.

Upper airway (UA) muscle activity is stimulated by changes in UA transmural pressure and by asphyxia. These responses are reduced by muscle relaxation. We hypothesized that this is due to a change in afferent feedback in the ansa hypoglossi and/or superior laryngeal nerve (SLN). We examined 1) the glossopharyngeal motor responses to UA transmural pressure and asphyxia and 2) how these responses were changed by muscle relaxation in animals where one or both of these afferent pathways had been sectioned bilaterally. Experiments were performed in 24 anesthetized, thoracotomized, artificially ventilated rats. Baseline glossopharyngeal activity and its response to UA transmural pressure and asphyxia were moderately reduced after bilateral section of the ansa hypoglossi (P < 0.05). Conversely, bilateral SLN section increased baseline glossopharyngeal activity, augmented the response to asphyxia, and abolished the response to UA transmural pressure. Muscle relaxation reduced resting glossopharyngeal activity and the response to asphyxia (P < 0.001). This occurred whether or not the ansa hypoglossi, the SLN, or both afferent pathways had been interrupted. We conclude that ansa hypoglossi afferents tonically excite and SLN afferents tonically inhibit UA motor activity. Muscle relaxation depressed UA motor activity after section of the ansa hypoglossi and SLN. This suggests that some or all of the response to muscle relaxation is mediated by alterations in the activity of afferent fibers other than those in the ansa hypoglossi or SLN.     

Role of phrenic nerve afferents in the control of breathing

A long-held belief is that respiratory-related reflexes mediated by afferents in the diaphragm are weak or absent. However, recent data suggest that diaphragmatic afferents are capable of altering ventilatory motor drive as well as influencing perception of added inspiratory loads in humans. This review describes the sensory elements of the diaphragm, their central projections, and their functional significance in the control of respiratory muscle activation. The reflexes elicited by electrical stimulation of phrenic nerve afferents and the contribution of diaphragmatic afferents in respiratory load compensation and perception are considered. There is growing evidence that phrenic nerve afferents are activated under a variety of conditions. However, the significance of this input to the central nervous system is yet to be discerned.     

Diaphragmatic blood flow in the dog

In anesthetized mongrel dogs we measured the blood flow in the left phrenic artery (Qdi), using an electromagnetic flow probe, before and during supramaximal phrenic nerve stimulation (pacing). This was done at constant respiratory rate (24/min) but at three different stimulation frequencies at a duty cycle of 0.4 (20, 50, and 100 Hz) and at three different duty cycles at a stimulation frequency of 50 Hz (duty cycle = 0.2, 0.4, and 0.8). Qdi was unchanged during diaphragm contraction until transdiaphragmatic pressure (Pdi) was greater than approximately 11 cmH2O, whereafter it began to decrease, reaching zero at Pdi approximately 20 cmH2O. Thus, when Pdi was greater than 21 cmH2O, all flow occurred during relaxation. Qdi averaged over the entire respiratory cycle (Qt) was less at duty cycle = 0.8 than under the other conditions. This was because of decreasing length of relaxation phase rather than a difference of relaxation phase flow (Qr), which was maximal during all conditions of phrenic stimulation. During pacing-induced fatigue, Qt actually rose slightly as Pdi fell. This was due to an increase in contraction phase flow while Qr remained constant. The relationship between Qt and tension-time index was not unique but varied according to the different combinations of duty cycle and stimulus frequency.     

Diaphragm afferent modulation of phrenic motor drive

Experiments were performed in eight lightly anesthetized thiopental sodium (Pentothal) cats to examine whether diaphragmatic afferents can significantly alter the neural drive to the diaphragm when the animal is exposed to lower body negative pressure. Moving-time-averaged diaphragmatic electromyograms (EMGma) were recorded and compared before and during exposure to lower body negative pressure in each of three consecutive conditions: C7 spinalization, bilateral vagotomy, and cervical dorsal rhizotomy. Application of lower body negative pressure in C7-spinalized animals resulted in a decrease in inspiratory time and peak diaphragmatic activity compared with control levels. After bilateral vagotomy, EMGma activity was prolonged with the application of lower body negative pressure. However, there was no increase in peak EMGma activity. After transection of the cervical dorsal roots subserving the phrenic nerve, the prolongation of diaphragmatic activity negative was eliminated. Therefore, we conclude that the significant increase in duration of inspiration in response to application of lower body negative pressure in the C7-spinalized, bilaterally vagotomized cat is mediated by phrenic nerve afferents.     

The role of reflex mechanisms in postinhibitory rebound studied by analysis of human single motor unit activity

The mechanism of onset of rebound after inhibition induced by electrical stimulation of a nerve of maximal and submaximal strength for M-response was studied in single motor units of normal human soleus, rectus femoris, and hand muscles. Poststimulus histograms and changes in the duration of interspike intervals were compared with mechanical recordings of muscle contractions. In all muscles tested, during strong isotonic contraction, the increase in motor unit activity after a silent period was partly due to synchronization of their emergence from inhibition. However, it also contained a component of true facilitation of motoneurons, which was evidently a reflex response to lengthening of the muscle in the relaxation phase after evoked contraction. The latent period of this facilitation in the soleus and rectus femoris muscles coincided in value with the latent period of the monosynaptic spinal reflex, whereas in the hand muscles, in which a monosynaptic response to electrical nerve stimulation could not be evoked, the latent period of facilitation as a result of spindle activation during muscle relaxation was significantly longer than the latent period of the monosynaptic reflex. These findings support the hypothesis of presynaptic suppression of monosynaptic connections of Ia afferents with the motoneurons of some human muscles by descending tonic influences and of the use of information coming from spindles by supraspinal levels of the CNS.     

Effect of abdominal compression on diaphragmatic tendon organ activity.

Previous studies suggest that afferents in the diaphragm participate in the reflex reduction in phrenic nerve efferent activation when the length of the diaphragm is increased by abdominal compression. The present study determined the response of tendon organ afferents in the diaphragm to increases in abdominal pressure. Five cats were anesthetized with thiopental sodium (60 mg/kg ip to induce, supplemented intravenously). Extracellular recordings from nine individual tendon organ afferents were made from right cervical dorsal root ganglia 5 and 6. Right crural electromyographic activity was recorded. The right extrathoracic phrenic nerve was isolated and stimulated to identify tendon organs on the basis of conduction velocity and response to twitch. The response to ramp-and-hold stretch of the diaphragm was used as an additional test to differentiate tendon organs from muscle spindles. The mean level of activity of the tendon organs during the 1st s of the inspiratory phase was 47 +/- 10 (SD) Hz. Abdominal compression was associated with a significant increase in the activity of these afferents to 61 +/- 11 Hz. Results indicate that increases in the activity of diaphragmatic tendon organs are associated with moderate increases in abdominal pressure and are likely the result of elevations in the active tension developed by the diaphragm. Combined with results from previous studies, it is possible that diaphragmatic tendon organs may play a role in the attenuation of respiratory muscle activation when abdominal pressure is increased.     

CO2 sensitivity of cat phrenic neurogram during hypoxic respiratory depression

The CO2 response of the phrenic neurogram before and during CO-induced isocapnic brain hypoxia was studied in peripherally chemodenervated, vagotomized, paralyzed, ventilated cats with blood pressure held constant. During inhalation of 0.5% CO in 40% O2, arterial O2 content (CaO2) was reduced to 40% and minute phrenic activity to 38.4 +/- 9.4% (SE; n = 9) of prehypoxic levels, primarily due to depression of peak phrenic amplitude (PP). CO2 response, defined as the slope of the plot of PP vs. end-tidal PCO2 during CO2 rebreathing, was unaffected by phrenic depression even to the point of total suppression of phrenic activity in two cats. The effect of the tissue metabolic acidosis associated with hypoxia on phrenic CO2 sensitivity was assessed in a separate group of cats by blocking lactate formation during hypoxia with dichloroacetate (DCA). Preventing lactic acidosis during hypoxia did not affect the CO2 response of the phrenic activity during hypoxia. We conclude that 1) hypoxic depression does not limit the ability of central respiratory neurons to respond to CO2, and 2) the failure of DCA to affect the CO2 response of the phrenic neurogram suggests that brain intracellular lactic acidosis does not modify the phrenic response to hypercapnia.     

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

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