Time of application of negative pressure pulses and upper airway muscle activity

Effect of upper airway pressure changes on thoracic inspiratory muscles has been shown to depend on the time of application during the breathing cycle. The present study was designed to investigate the importance of the time of application of upper airway negative pressure pulses on upper airway muscles. The upper airway was functionally isolated into a closed system in 24 anesthetized spontaneously breathing rabbits. Negative pressure pulses were applied in early (within the first 200 ms) and late (greater than or equal to 200 ms) inspiration, while electromyograms (EMG) of the diaphragm (Dia), genioglossus (GG), alae nasi (AN), and/or posterior cricoarytenoid (PCA) muscles were simultaneously monitored. When negative pressure pulse was applied in early inspiration, the increase in GG activity was greater [0.49 +/- 0.37 to 4.24 +/- 3.71 arbitrary units (AU)] than when negative pressure was applied in late inspiration (0.44 +/- 0.29 to 2.64 +/- 3.05 AU). Similarly, increased activation of AN (2.63 +/- 1.01 to 4.26 +/- 1.69 AU) and PCA (3.46 +/- 1.16 to 6.18 +/- 2.93 AU) was also observed with early inspiratory application of negative pressure pulses; minimal effects were seen in these muscles with late application. An inhibitory effect on respiratory timing consisting of a prolongation in inspiration (TI) and a decrease in peak Dia EMG/TI was observed as previously reported. These results indicate that the time of application of negative pressure during the breathing cycle is an important variable in determining the magnitude of the response of upper airway muscles.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genioglossus and alae nasi activity in fetal sheep

The functional development of two upper airway dilating muscles, the alae nasi and the genioglossus, has been studied in fetal sheep in utero from 112-140 days gestation. Before electrocortical differentiation phasic activity was present in both muscles for long periods, mostly when breathing movements were present. After 120 days gestation phasic genioglossal and alae nasi activity occurred only during periods of low voltage electrocortical activity. During high voltage episodes there was no phasic activity and tonic activity was not sustained. Although present during periods of breathing movements genioglossus activity was rarely synchronous with the diaphragm. The alae nasi showed both respiratory and non-respiratory related activity. Hypoxia abolished both alae nasi and genioglossus activity but whereas alae nasi rapidly developed an inspiratory rhythm during 5% CO2 administration this was not the case with the genioglossus and inspiratory activity was not always seen in the genioglossus even during 10% CO2 administration. It is concluded that there are fundamental differences between the control of genioglossus and alae nasi activity in the fetal sheep. The alae nasi behaves as an inspiratory muscle responding to hypoxia and hypercapnia as would be expected but the genioglossus shows no inspiratory activity during normal unstimulated fetal breathing. Thus the neural mechanisms for activation of inspiratory activity appear to be present late in gestation. However it is possible for the genioglossus to develop an inspiratory rhythm under conditions of much increased respiratory drive.     

Mechanisms of control of alae nasi muscle activity.

Human upper airway dilator muscles are clearly influenced by chemical stimuli such as hypoxia and hypercapnia. Whether in humans there are upper airway receptors capable of modifying the activity of such muscles is unclear. We studied alae nasi electromyography (EMG) in normal men in an attempt to determine 1) whether increasing negative intraluminal pressure influences the activity of the alae nasi muscle, 2) whether nasal airway feedback mechanisms modify the activity of this muscle, and 3) if so, whether these receptor mechanisms are responding to mucosal temperature/pressure changes or to airway deformation. Alae nasi EMG was recorded in 10 normal men under the following conditions: 1) nasal breathing (all potential nasal receptors exposed), 2) oral breathing (nasal receptors not exposed), 3) nasal breathing with splints (airway deformation prevented), and 4) nasal breathing after nasal anesthesia (mucosal receptors anesthetized). In addition, in a separate group, the combined effects of anesthesia and nasal splints were assessed. Under each condition, EMG activity was monitored during basal breathing, progressive hypercapnia, and inspiratory resistive loading. Under all four conditions, both load and hypercapnia produced a significant increase in alae nasi EMG, with hypercapnia producing a similar increment in EMG regardless of nasal receptor exposure. On the other hand, loading produced greater increments in EMG during nasal than during oral breathing, with combined anesthesia plus splinting producing a load response similar to that observed during oral respiration. These observations suggest that nasal airway receptors have little effect on the alae nasi response to hypercapnia but appear to mediate the alae nasi response to loading or negative airway pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in upper airway muscle activation and ventilation during phasic REM sleep in normal men

Several investigators have observed that irregular breathing occurs during rapid-eye-movement (REM) sleep in healthy subjects, with ventilatory suppression being prominent during active eye movements [phasic REM (PREM) sleep] as opposed to tonic REM (TREM) sleep, when ocular activity is absent and ventilation more regular. Inasmuch as considerable data suggest that rapid eye movements are a manifestation of sleep-induced neural events that may importantly influence respiratory neurons, we hypothesized that upper airway dilator muscle activation may also be suppressed during periods of active eye movements in REM sleep. We studied six normal men during single nocturnal sleep studies. Standard sleep-staging parameters, ventilation, and genioglossus and alae nasi electromyograms (EMG) were continuously recorded during the study. There were no significant differences in minute ventilation, tidal volume, or any index of genioglossus or alae nasi EMG amplitude between non-REM (NREM) and REM sleep, when REM was analyzed as a single sleep stage. Each breath during REM sleep was scored as "phasic" or "tonic," depending on its proximity to REM deflections on the electrooculogram. Comparison of all three sleep states (NREM, PREM, and TREM) revealed that peak inspiratory genioglossus and alae nasi EMG activities were significantly decreased during PREM sleep compared with TREM sleep [genioglossus (arbitrary units): NREM 49 +/- 12 (mean +/- SE), TREM 49 +/- 5, PREM 20 +/- 5 (P less than 0.05, PREM different from TREM and NREM); alae nasi: NREM 16 +/- 4, TREM 38 +/- 7, PREM 10 +/- 4 (P less than 0.05, PREM different from TREM)]. We also observed, as have others, that ventilation, tidal volume, and mean inspiratory airflow were significantly decreased and respiratory frequency was increased during PREM sleep compared with both TREM and NREM sleep. We conclude that hypoventilation occurs in concert with reduced upper airway dilator muscle activation during PREM sleep by mechanisms that remain to be established.     

Respiratory changes in nasal muscle length

Respiratory changes in alae nasi muscle length were recorded using sonomicrometry in pentobarbital sodium-anesthetized tracheostomized dogs spontaneously breathing 100% O2. Piezoelectric crystals were inserted via small incisions into the alae nasi of 11 animals, and bipolar fine-wire electrodes were inserted contralaterally in nine of the same animals. The alae nasi shortened during inspiration in all animals. The mean amount of shortening was 1.33 +/- 0.22% of resting length (LR), and the mean velocity of shortening during the first 200 ms was 4.60 +/- 0.69% LR/S. The onset of alae nasi shortening preceded inspiratory flow by 77 +/- 18 ms (P less than 0.002), at which time both alae nasi shortening and the moving average of electromyographic (EMG) activity had reached approximately one-third of their peak values. In contrast, there was a relative delay in alae nasi relaxation relative to the decay of alae nasi EMG at the end of expiration. Single-breath airway occlusions at end expiration changed the normally rounded pattern of alae nasi shortening and moving average EMG to a late-inspiratory peaking pattern; both total shortening and EMG were increased by similar amounts. The onset of vagally mediated volume-related inhibition of alae nasi shortening occurred synchronously with the onset of inhibition of alae nasi EMG; both occurred at lung volumes substantially below tidal volume. These results indicate that the pattern of inspiratory shortening of this nasal dilating muscle is reflected closely in the pattern of EMG activity and that vagal afferents cause substantial inhibition of alae nasi inspiratory shortening.     

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.     

Effect of phrenic afferent stimulation on pattern of respiratory muscle activation.

Ventilation and electromyogram (EMG) activities of the right hemidiaphragm, parasternal intercostal, triangularis sterni, transversus abdominis, genioglossus, and alae nasi muscles were measured before and during central stimulation of the left thoracic phrenic nerve in 10 alpha-chloralose anesthetized vagotomized dogs. Pressure in the carotid sinuses was fixed to maintain baroreflex activity constant. The nerve was stimulated for 1 min with a frequency of 40 Hz and stimulus duration of 1 ms at voltages of 5, 10, 20, and 30 times twitch threshold (TT). At five times TT, no change in ventilation or EMG activity occurred. At 10 times TT, neither tidal volume nor breathing frequency increased sufficiently to reach statistical significance, although the change in their product (minute ventilation) was significant (P less than 0.05). At 20 and 30 times TT, increases in both breathing frequency and tidal volume were significant. At these stimulus intensities, the increases in ventilation were accompanied by approximately equal increases in the activity of the diaphragm, parasternal, and alae nasi muscles. The increase in genioglossus activity was much greater than that of the other inspiratory muscles. Phrenic nerve stimulation also elicited inhomogeneous activation of the expiratory muscles. The transversus abdominis activity increased significantly at intensities from 10 to 30 times TT, whereas the activity of the triangularis sterni remained unchanged. The high stimulation intensities required suggest that the activation of afferent fiber groups III and IV is involved in the response. We conclude that thin-fiber phrenic afferent activation exerts a nonuniform effect on the upper airway, rib cage, and abdominal muscles and may play a role in the control of respiratory muscle recruitment.     

Alae nasi electromyographic activity and timing in obstructive sleep apnea

The alae nasi is an accessible dilator muscle of the upper airway located in the nose. We measured electromyograms (EMG) of the alae nasi to determine the relationship between their activity and timing to contraction of the rib cage muscles and diaphragm during obstructive apnea in nine patients. Alae nasi EMG were measured with surface electrodes and processed to obtain a moving time average. Contraction of the rib cage and diaphragm during apneas was detected with esophageal pressure. During non-rapid-eye-movement (NREM) sleep, there was a significant correlation in each patient between alae nasi EMG activity and the change in esophageal pressure. During rapid-eye-movement (REM) sleep, correlations were significantly lower than during NREM sleep. As the duration of each apnea increased, the activation of alae nasi EMG occurred progressively earlier than the change in esophageal pressure. We conclude that during obstructive apneas in NREM sleep, activity of the alae nasi increases when diaphragm and rib cage muscle force increases and the activation occurs earlier as each apneic episode progresses.     

Effect of sleep state and hypercapnia on alae nasi and diaphragm EMGs in preterm infants

A coordinated activation of upper airway and chest wall muscles may be crucial in maintaining airway patency and ventilation. The alae nasi (AN) and diaphragm (DIA) electromyograms (EMG) were recorded with surface electrodes in 17 unsedated healthy preterm infants during both active (AS) and quiet sleep (QS). Airflow was measured via a nasal mask pneumotachograph and integrated to obtain tidal volume. Studies were performed during inhalation of room air and mixtures of 2 and 4% CO2 in air. In room air, phasic AN EMG accompanied 45 +/- 7% of breaths during AS compared with 14 +/- 5% of breaths during QS (P less than 0.001); however, with inhalation of 4% CO2 the incidence of AN EMG increased to comparable levels in both sleep states. During room air breathing onset of AN EMG preceded that of the DIA EMG and inspiratory airflow by 41 +/- 8 ms (P less than 0.01) and 114 +/- 29 ms (P less than 0.05), respectively. Peak AN activity preceded peak DIA activity by 191 +/- 36 ms (P less than 0.01). Alteration in sleep state or increasing chemical drive did not significantly alter these temporal relationships. Nevertheless, with each increase in end-tidal CO2, peak DIA EMG and tidal volume increased while peak AN EMG only showed a consistent increase during 4% CO2 inhalation. We conclude that although there exists a mechanism that temporally coordinates AN and DIA activation, the amount of AN EMG activity with each breath is not clearly correlated with DIA activation, which may contribute to the high incidence of respiratory dysrhythmias in preterm neonates.     

Response of genioglossus muscle activity to nasal airway occlusion in normal sleeping adults

To determine the combined effect of increased subatmospheric upper airway pressure and withdrawal of phasic volume feedback from the lung on genioglossus muscle activity, the response of this muscle to intermittent nasal airway occlusion was studied in 12 normal adult males during sleep. Nasal occlusion at end expiration was achieved by inflating balloon-tipped catheters located within the portals of a nose mask. No seal was placed over the mouth. During nose breathing in non-rapid-eye-movement (NREM) sleep, nasal airway occlusion resulted in multiple respiratory efforts before arousal. Mouth breathing was not initiated until arousal. Phasic inspiratory genioglossus activity was present in eight subjects during NREM sleep. In these subjects, comparison of peak genioglossus inspiratory activity on the first three occluded efforts to the value just before occlusion showed an increase of 4.7, 16.1, and 28.0%, respectively. The relative increases in peak genioglossus activity were very similar to respective increases in peak diaphragm activity. Arousal was associated with a large burst in genioglossus activity. During airway occlusion in rapid-eye-movement (REM) sleep, mouth breathing could occur without a change in sleep state. In general, genioglossus responses to airway occlusion in REM sleep were similar in pattern to those in NREM sleep. A relatively small reflex activation of upper airway muscles associated with a sudden increase in subatmospheric pressure in the potentially collapsible segment of the upper airway may help compromise upper airway patency during sleep.     

Influence of nasal airflow temperature and pressure on alae nasi electrical activity.

The influence of nasal airflow, temperature, and pressure on upper airway muscle electromyogram (EMG) was studied during steady-state exercise in five normal subjects. Alae nasi (AN) and genioglossus EMG activity was recorded together with nasal and oral airflows and pressures measured simultaneously by use of a partitioned face mask. At constant ventilations between 30 and 50 l/min, peak inspiratory AN activity during nasal breathing (7.2 +/- 1.4 arbitrary units) was greater than that during oral breathing (1.0 +/- 0.3 arbitrary units; P less than 0.005). In addition, the onset of AN EMG activity preceded inspiratory flow by 0.38 +/- 0.03 s during nasal breathing but by only 0.17 +/- 0.04 s during oral breathing (P less than 0.04). When the subject changed from nasal to oral breathing, both these differences were apparent on the first breath. However, peak AN activity during nasal breathing was uninfluenced by inspiration of hot saturated air (greater than 40 degrees C), by external inspiratory nasal resistance, or by changes in the expiratory route. The genioglossus activity did not differ between nasal and oral breathing (n = 2). Our findings do not support reflex control of AN activity sensitive to nasal flow, temperature, or surface pressure. We propose a centrally controlled feedforward modulation of phasic inspiratory AN activity linked with the tonic drive to the muscles determining upper airway breathing route.     

Influence of upper airway sensory receptors on respiratory muscle activation in humans

We reasoned that neural information from upper airway (UA) sensory receptors could influence the relationship between UA and diaphragmatic neuromuscular responses to hypercapnia. In this study, the electromyographic (EMG) activities of the alae nasi (AN), genioglossus (GG), and chest wall (CW) or diaphragm (Di) to ventilatory loading were assessed in six laryngectomized, tracheostomized human subjects and in six subjects breathing with an intact UA before and after topical UA anesthesia. The EMG activities of the UA and thoracic muscles increased at similar rates with increasing hypercapnia in normal subjects, in subjects whose upper airways were anesthetized, and in laryngectomized subjects breathing with a cervical tracheostomy. Furthermore, in the laryngectomized subjects, respiratory muscle EMG activation increased with resistive inspiratory loading (15 cmH2O X l-1 X s) applied at the level of a cervical tracheostomy. At an average expired CO2 fraction of 7.0%, resistive loading resulted in a 93 +/- 26.3% (SE) increase in peak AN EMG activity, a 39 +/- 2.0% increase in peak GG EMG activity, and a 43.2 +/- 16.5% increase in peak CW (Di) EMG activity compared with control values. We conclude that the ventilatory responses of the UA and thoracic muscles to ventilatory loading are not substantially influenced by laryngectomy or UA anesthesia.     

Involvement of pharyngeal muscles in compensatory responses of the respiration system to inspiration resistance load]

The present study was undertaken to test the hypothesis that recruitment of upper airway muscles in loaded breathing is a result of integration of peripheral chemoreceptor and pulmonary mechanoreceptor afferents. Experiments were performed in spontaneously breathing tracheostomized anesthetized rabbits. It had been studied the effects of inspiratory resistive loading to EMG activity of genioglossus muscle. In the intact rabbits the peak value and duration of inspiratory activity of genioglossus increased in loading. Imposition of resistive load in vagotomized animals did not evoke alteration in inspiratory activity of genioglossus in the first loaded breath. Hyperoxia decreased the response of genioglossus muscle to inspiratory loading and vagatomy. We conclude that hypoxic stimulation of peripheral chemoreceptors and decrease in volume-related afferent activity from pulmonary stretch receptors are major mechanisms of the upper airway muscle recruiment in inspiratory resistive loading.     

Breathing route influences upper airway muscle activity in awake normal adults

Both nasal obstruction and nasal anesthesia result in disordered breathing during sleep in humans, and bypassing the nasal route during tidal breathing in experimental animals produces decreased electromyographic activity of upper airway (UA) dilating muscles. To investigate UA responses to breathing route in normal awake humans, we studied eight healthy males (ages 21-38 yr) during successive trials of voluntary nose breathing (N), voluntary mouth breathing (M), and mouth breathing with nose occluded (MO). We measured genioglossus electromyographic activity (EMGgg) with perorally inserted bipolar electrodes, alae nasi (EMGan) and diaphragm EMG activity (EMGdi) with surface electrodes, and minute ventilation (VE) with a pneumotachograph. Mean phasic inspiratory EMG activity of both UA muscles was significantly greater during N than during M or MO, even when a 2.5-cmH2O.l-1.s inspiratory resistance was added to MO (P less than 0.01). In contrast, neither EMGdi nor VE was consistently affected by breathing route. EMGgg during N was significantly decreased after selective topical nasal anesthesia (P less than 0.002); a decrease in EMGan did not achieve statistical significance. These data suggest that peak UA dilating muscle activity may be modulated by superficial receptors in the nasal mucosa sensitive to airflow.     

Activation of masseter muscles with inspiratory resistance loading

Closure of the jaw exerts traction on muscles that insert on the hyoid bone and that may stabilize or expand the pharyngeal airway. We postulated that the masseter muscles, which close the jaw, would be activated when the patency of the pharyngeal airway is threatened. We therefore measured electromyographic activation of the masseters during inspiratory resistance loading and compared it with activation of chin muscles and alae nasi in 10 normal subjects. We observed no masseter activation during quiet unloaded breathing, but as pharyngeal pressure became lower there was a significant increase in masseter activation in all subjects. The change in masseter activation relative to pharyngeal pressure was similar to that of chin muscles and alae nasi. Activation of the masseter preceded the fall in pharyngeal pressure as also occurred in the chin muscles and alae nasi. We conclude that the masseters are activated by inspiratory resistance loading and have respiratory activity similar to pharyngeal airway muscles.     

Respiratory muscle responses to changes in chemoreceptor drive in infants

Upper airway muscles and the diaphragm may have different quantitative responses to chemoreceptor stimulation. To compare the respiratory muscle responses to changes in CO2, 10 ventilator-dependent preterm infants (gestational age 28 +/- 1 wk, postnatal age 40 +/- 6 days, weight 1.4 +/- 0.1 kg) were passively hyperventilated to apnea and subsequently hypoventilated. Electromyograms from the genioglossus, alae nasi, posterior cricoarytenoid, and diaphragm were recorded from surface electrodes. Apneic CO2 thresholds of all upper airway muscles (genioglossus 46.8 +/- 4.3 Torr, alae nasi 42.4 +/- 3.6 Torr, posterior cricoarytenoid 41.6 +/- 3.2 Torr) were higher than those of the diaphragm (38.8 +/- 2.6 Torr, all P less than 0.05). Above their CO2 threshold levels, responses of all upper airway muscles appeared proportional to those of the diaphragm. We conclude that nonproportional responses of the respiratory muscles to hypercapnia may be the result of differences in their CO2 threshold. These differences in CO2 threshold may cause imbalance in respiratory muscle activation with changes in chemical drive, leading to upper airway instability and obstructive apnea.     

Fluctuation in timing of upper airway and chest wall inspiratory muscle activity in obstructive sleep apnea

An imbalance in the amplitude of electrical activity of the upper airway and chest wall inspiratory muscles is associated with both collapse and reopening of the upper airway in obstructive sleep apnea (OSA). The purpose of this study was to examine whether timing of the phasic activity of these inspiratory muscles also was associated with changes in upper airway caliber in OSA. We hypothesized that activation of upper airway muscle phasic electrical activity before activation of the chest wall pump muscles would help preserve upper airway patency. In contrast, we anticipated that the reversal of this pattern with delayed activation of upper airway inspiratory muscles would be associated with upper airway narrowing or collapse. Therefore the timing and amplitude of midline transmandibular and costal margin moving time average (MTA) electromyogram (EMG) signals were analyzed from 58 apnea cycles in stage 2 sleep in six OSA patients. In 86% of the postapnea breaths analyzed the upper airway MTA peak activity preceded the chest wall peak activity. In 86% of the obstructed respiratory efforts the upper airway MTA peak activity followed the chest wall peak activity. The onset of phasic electrical activity followed this same pattern. During inspiratory efforts when phasic inspiratory EMG amplitude did not change from preapnea to apnea, the timing changes noted above occurred. Even within breaths the relative timing of the upper airway and chest wall electrical activities was closely associated with changes in the pressure-flow relationship. We conclude that the relative timing of inspiratory activity of the upper airway and chest wall inspiratory muscles fluctuates during sleep in OSA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Upper airway muscle and diaphragm responses to hypoxia in the piglet

The neonatal ventilatory response to hypoxia is characterized by initial transient stimulation and subsequent respiratory depression. It is unknown, however, whether this response is also exhibited by the upper airway muscles that regulate nasal, laryngeal, and pharyngeal patency. We therefore compared electromyogram (EMG) amplitudes and minute EMGs for the diaphragm (DIA), alae nasi (AN), posterior cricoarytenoid (PCA), and genioglossus (GG) muscles in 12 anesthetized spontaneously breathing piglets during inhalation of 12% O2 over 10 min. Minute EMG for the DIA responded to hypoxia with an initial transient increase and subsequent return to prehypoxia levels by 10 min. Hypoxia also stimulated all three upper airway muscles. In contrast to the DIA EMG, however, AN, PCA, and GG EMGs all remained significantly above prehypoxia levels after 10 min of hypoxia. We have thus demonstrated that the initial stimulation and subsequent depression of the DIA EMG after 12% O2 inhalation contrast with the sustained increase in AN, PCA, and GG EMGs during hypoxia. We speculate that 1) central inhibition during neonatal hypoxia is primarily distributed to the motoneuron pools regulating DIA activation and 2) peripheral chemoreceptor stimulation and/or central disinhibition induced by hypoxia preferentially influence those motoneuron pools that regulate upper airway muscle activation, causing the different hypoxic responses of these muscle groups in the young piglet.     

Effect of intestinal afferent stimulation on pattern of respiratory muscle activation

The purpose of the present study was to examine the reflex effects of mechanical stimulation of intestinal visceral afferents on the pattern of respiratory muscle activation. In 14 dogs anesthetized with pentobarbital sodium, electromyographic activity of the costal and crural diaphragm, parasternal intercostal, and upper airway respiratory muscles was measured during distension of the small intestine. Rib cage and abdominal motion and tidal volume were also recorded. Distension produced an immediate apnea (11.16 +/- 0.80 s). During the first postapneic breath, costal (43 +/- 7% control) and crural (64 +/- 6% control) activity were reduced (P less than 0.001). In contrast, intercostal (137 +/- 11%) and upper airway muscle activity, including alae nasi (157 +/- 16%), genioglossus (170 +/- 15%), and posterior cricoarytenoid muscles (142 +/- 7%) all increased (P less than 0.005). There was greater outward rib cage motion although the abdomen moved paradoxically inward during inspiration, resulting in a reduction in tidal volume (82 +/- 6% control) (P less than 0.005). Postvagotomy distension produced a similar apnea and subsequent reduction in costal and crural activity. However, enhancement of intercostal and upper airway muscle activation was abolished and there was a greater fall in tidal volume (65 +/- 14%). In conclusion, mechanical stimulation of intestinal afferents affects the various inspiratory muscles differently; nonvagal afferents produce an initial apnea and subsequent depression of diaphragm activity whereas vagal pathways mediate selective enhancement of intercostal and upper airway muscle activation.     

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.