Vagal Feedback Research Articles

Assessing baroreflex sensitivity by the transfer function method: what are we really measuring?

by governing the autonomic outflow to the heart and blood vessels, arterial baroreceptors play a central role in controlling short-term blood pressure responses to the hemodynamic perturbations continuously occurring in daily life. Abnormalities in baroreflex function are thought to play an

Determinants of heart rate variability in obstructive sleep apnea syndrome during wakefulness and sleep.

Heart rate variability (HRV) is mediated by at least three primary mechanisms: 1) vagal feedback from pulmonary stretch receptors (PSR), 2) central medullary coupling between respiratory and cardiovagal neurons (RCC), and 3) arterial baroreflex (ABR)-induced fluctuations. We employed a noninvasive experimental protocol in conjunction with a minimal model to determine how these sources of HRV are altered in obstructive sleep apnea syndrome (OSAS). Respiration, heart rate, and blood pressure were monitored in eight normal subjects and nine untreated OSAS patients in relaxed wakefulness and stage 2 and rapid eye movement sleep. A computer-controlled ventilator delivered inspiratory pressures that varied randomly from breath to breath. Application of the model to the corresponding subject responses allowed the delineation of the three components of HRV. In all states, RCC gain was lower in OSAS patients than in normal subjects (P < 0.04). ABR gain was also reduced in OSAS patients (P < 0.03). RCC and ABR gains increased from wakefulness to sleep (P < 0.04). However, there was no difference in PSR gain between subject groups or across states. The findings of this study suggest that the adverse autonomic effects of OSAS include impairment of baroreflex gain and central respiratory-cardiovascular coupling, but the component of respiratory sinus arrhythmia that is mediated by lung vagal feedback remains intact.

C-fiber activation exacerbates sleep-disordered breathing in rats.

We reported previously that activation of vagal feedback by protoveratrines or serotonin exacerbates sleep apnea in rats, but each of these agents activates multiple afferent fiber types. To elucidate the specific impact of C-fiber activity on sleep apnea, the present study utilized capsaicin (CAP), which stimulates C-fibers via the CAP receptor. Nine adult Sprague-Dawley rats were instrumented for chronic polysomnography and recorded for 6 hours on four occasions. Prior to each recording, the animals received an intraperitoneal injection of either saline (control), or CAP 0.1, 1.0, or 10.0 mg/kg. Respiration was monitored by single-chamber plethysmography and apneas were scored as breaths longer than 2.5 seconds not preceded by a sigh. CAP increased apneas during non-rapid eye movement (NREM) sleep (p < 0.05 vs control) and reduced respiratory minute ventilation by about 15% in all behavioral states (waking, NREM, and REM sleep). We conclude that selective pharmacological activation of C-fibers produces a diathesis of sleep-disordered breathing specific to NREM sleep in rats.

Termination of inspiration by phase-dependent respiratory vagal feedback in awake normal humans.

Imperceptible levels of proportional assist ventilation applied throughout inspiration reduced inspiratory time (TI) in awake humans. More recently, the reduction in TI was associated with flow assist, but flow assist also reaches a maximum value early during inspiration. To test the separate effects of flow assist and timing of assist, we applied a pseudorandom binary sequence of flow-assisted breaths during early, late, or throughout inspiration in eight normal subjects. We hypothesized that imperceptible flow assist would shorten TI most effectively when applied during early inspiration. Tidal volume, integrated respiratory muscle pressure per breath, TI, and TE were recorded. All stimuli (early, late, or flow assist applied throughout inspiration) resulted in a significant increase in inspiratory flow; however, only when the flow assist was applied during early inspiration was there a significant reduction in TI and the integrated respiratory muscle pressure per breath. These results provide further evidence that vagal feedback modulates breathing on a breath-by-breath basis in conscious humans within a physiological range of breath sizes.

Vagal feedback is essential for breathing in unanesthetized ground squirrels

The roles of vagal afferent feedback in terminating inspiration and modulating breathing pattern and ventilatory responses to hypoxia and hypercapnia were assessed in the golden-mantled ground squirrel, Spermophilus lateralis, during wakefulness and urethane anesthesia. Hypoxia increased ventilation primarily through increases in breathing frequency (f R) while hypercapnia increased ventilation primarily through increases in tidal volume (V T) in both anesthetized and unanesthetized animals. Vagotomy resulted in an increase in tidal volume, a decrease in breathing frequency and ventilation, and depressed ventilatory responses to both hypoxia and hypercapnia in anesthetized animals. In unanesthetized animals vagotomy produced a transient ‘gasp-like’ breathing pattern that rapidly progressed to a non-obstructive central apnea. These data indicate that vagal feedback shapes ventilation on a breath-by-breath basis during anesthesia and is essential for ventilation in unanesthetized animals. The mechanisms that transform the influences of vagal input on breathing between anesthetized and unanesthetized states remain unclear. Changes in breathing pattern induced by the removal of vagal feedback compromise chemoreflexes.

Evidence of a Functional Role in Lung Inflation for the Buccal Pump in the Agamid Lizard Uromastyx Aegyptius Microlepis

This study has demonstrated that the agamid desert lizard Uromastyx aegyptius microlepis ventilates its lungs both with a triphasic, thoracic aspiratory pump and by gulping air, using a buccal pump. These two mechanisms never occur simultaneously because bouts of buccal pumping are always initiated after the passive expiration that terminates a thoracic breath. Lung inflation arising from thoracic and buccal ventilation was confirmed by direct recording of volume changes using a whole-body plethysmograph. This observation was further confirmed by mechanical separation of the inflationary pressures associated with these two breathing mechanisms, enabling the effects of lung inflation on buccal breathing to be observed. This revealed that the buccal pump is influenced by a powerful Hering-Breuer-type reflex, further confirming its role in lung inflation. Bilateral thoracic vagotomy tended to increase the variance of the amplitude and duration of the breaths associated with the aspiration pump and abolished the effects of lung inflation on the buccal pump. Uromastyx has vagal afferents from pulmonary receptors that respond to changes in lung volume and appear not to be sensitive to CO2. This study describes two lung-inflation mechanisms (an amphibian-like buccal pump and a mammalian-like aspiration pump) in a single extant amniote, both of which are subject to vagal feedback control.

Distribution and classification of respiratory neurones in the nucleus tractus solitarius of the rat medulla and their responses to central and periphereal stimuli

In the cat the dorsal respiratory group comprising the nucleus tractus solitarius (NTS) is regarded as an important respiratory centre. However the relevance of this nucleus in the control of respiration in the rat is still unclear. The present work aimed to identify and localize the various neurons involved in respiration in the nucleus tractus solitarius region of the rat medulla. Further, we intended to study the responses of these identified respiratory neurons to central and peripheral stimulation, in particular: 1)effect of stimulation of midbrain periaqueductal gray (PAG) matter and, 2)effect of stimulation of the vagus (vagal feedback). Nembutal-anaesthetised (80 mg/Kg), spontaneously-breathing rats (n = 60, 300–400 g) were used for the study. Neurons firing in relation to diaphragm electromyogram (dEMG) were located between 0.6–1.5 mm lateral to the midline, extending 0.5 mm caudal to 1.8 mm rostral to the posterior end of the area postrema (AP). Four different populations of respiratory-related neurons were recorded. They have been classified (with reference to dEMG) as: expiratory-inspiratory phase-spanning cells, early inspiratory neurons (eI-cells), cells that fire only in phase with diaphragm (I-all cells), and expiratory cells. The phase-spanning and eI-cell populations were located both in the ventrolateral and ventromedial NTS rostral to the area postrema, while the other cells were found predominantly in the more lateral regions. eI-cells were observed to start firing up to 20 ms prior to dEMG and ceased firing about one third of the way through diaphragm activity. They also showed a decrementing discharge pattern. Excitatory amino acid (DLH, 15–60 nl of 0.2 M) stimulation of PAG along its dorso-ventral axis produced dose-dependent changes in the cardiorespiratory parameters: increased respiratory frequency, decreased inspiratory and expiratory durations, increased blood pressure (BP) and heart rate. PAG stimulation elicited increases in activity in both phase-spanning and eI-neuronal populations in the NTS. The PAG sites evoking an increase in the phase-spanning cell activity were located more laterally than the PAG sites that led to increased eI-cell activity. The increase in the responses of the phase-spanning neurons was not accompanied by any changes in the respiratory frequency, whereas the PAG stimulation giving rise to an increase in eI-neuronal activity also elicited simultaneous increases in dEMG and the respiratory frequency. The central end of the cut vagus was electrically stimulated to activate pulmonary stretch-receptor afferents. Vagal stimulation caused depression of inspiratory cell activity along with bradycardia and a fall in BP. Both eI-neurons and I-all cells were inhibited. These cells exhibited a 'vagal escape' phenomenon ie, resuming activity whilst vagal stimulation continued. Phase-spanning cells and expiratory cells are yet to be tested for responses to vagal stimulation. The behaviours of these respiratory-related cells of the NTS, their temporal relationships with the dEMG, firing patterns, their responses to central and peripheral stimuli are discussed and a possible role for each in the brainstem control of respiration is proposed. Similar studies have also been carried out to elucidate the roles of ventrolateral column (VLM)/ventral respiratory group (VRG) neurons in the control of respiration in the rat. The findings of these studies are presented in an accompanying abstract.

Pulmonary vagal modulation of ventilation in toads (Bufo marinus)

This study examined the role of pulmonary vagal feedback on hypercapnic chemosensitivity and breathing pattern formation in cane toads ( Bufo marinus). Decerebrate, paralysed toads were uni-directionally ventilated with air, 2.5% CO 2 or 5.0% CO 2 with the lungs inflated or deflated, before and after pulmonary vagotomy. Motor output from the mandibular branch of the trigeminal nerve served as an index of fictive breathing. As respiratory drive was increased, breathing frequency increased and breaths were clustered into discrete episodes separated by periods of apnea. Lung deflation tended to enhance episodic breathing while inflation biased the system towards apnea at low levels of respiratory drive and a pattern of continuous, small breaths at higher levels of respiratory drive. Following bilateral pulmonary vagotomy there was no increase in ventilation during hypercapnia and lung inflation/deflation had no effect on breathing pattern. In isolated brainstem-spinal cord preparations from the same animals, all variables associated with fictive breathing were unaffected by changes in superfusate pH from 8.0 to 7.6. The breathing pattern from the in vitro preparations was highly variable. This study demonstrates a crucial role for vagal feedback in modulating respiration and the respiratory responses to hypercapnia in B. marinus.

Phrenic response to hypercapnia in the unanesthetized, decerebrate, newborn rat

We developed a decerebrate, vagotomized, newborn rat preparation to investigate brainstem respiratory control mechanisms without the influence of anesthesia, supra-pontine structures, or vagally mediated feedback mechanisms. We measured the changes in phrenic nerve electrical activity in response to breathing 3% and 5% CO 2 in unanesthetized, vagotomized, decerebrate newborn rats from 0 to 10 days of age and compared them with the changes in anesthetized, vagotomized, newborn rats and adult, vagotomized, decerebrate or anesthetized animals. Phrenic nerve activity was irregular in the young newborn rats and became more regular between 7 and 10 days of age. Ti and Ti/Ttot increased with age but increasing age had no influence on the response to CO 2. The response to CO 2 was dominated by increases in phrenic amplitude, minute activity, and inspiratory slope with no change in timing variables. These responses are similar to those that have been reported previously in vagally intact animals, suggesting that vagal feedback contributes little to the response to hypercapnia in the newborn rat. In summary, decerebrate newborn rats consistently respond to hypercapnia by increasing inspiratory drive similar to conscious animals.

CO2-sensitive olfactory and pulmonary receptor modulation of episodic breathing in bullfrogs.

Breathing was monitored during normocarbia, hypercarbia (6% CO2 in air), and the period immediately after the return to normocarbic conditions in intact, olfactory-denervated, and vagotomized bullfrogs. In intact frogs, ventilation increased during hypercarbia, but the breathing pattern remained episodic. Immediately upon return to air, there was a further paradoxical increase in breathing frequency, and breathing became continuous in most frogs. Results obtained from animals after olfactory receptor denervation indicate that tonic stimulation of olfactory receptors by airway CO2 inhibited breathing during hypercarbia. Measurements of the kinetics of changes in airway and arterial blood CO2 levels support the suggestion that the sudden release of this inhibition on the return to normocarbic conditions was responsible for the posthypercarbic hyperpnea. Vagotomy increased ventilation during normocarbia. Hypercarbia now caused a change in breathing pattern but had no net effect on total ventilation, suggesting that pulmonary vagal feedback inhibited ventilation during normocarbia but stimulated ventilation during hypercarbia. Although olfactory and pulmonary receptor feed-back shape the breathing pattern, they were not responsible for initiating or terminating the episodes of breathing.

Some effects of vagal blockade on abdominal muscle activation and shortening in awake dogs.

1. The mechanisms of abdominal muscle activation are thought to be different during expiratory threshold loading (ETL) compared with hypercapnia. Our objectives in the present study were to determine the effects of removing excitatory vagal feedback on abdominal muscle activation, shortening and pattern of recruitment during ETL and hypercapnia. Six tracheotomized dogs were chronically implanted with sonomicrometer transducers and fine wire EMG electrodes in each of the four abdominal muscles. Muscle length changes and EMG activity were studied in the awake dog during ETL (6 dogs) and CO2 rebreathing (3 dogs), before and after vagal blockade. 2. Following vagal blockade, the change in volume (increase in functional residual capacity, FRC) during ETL was greater and active phasic shortening of all the abdominal muscles was reduced, when shortening was compared with a similar change in lung volume. Similarly, at comparable minute ventilation, abdominal muscle active shortening was also reduced during hypercapnia. The internal muscle layer was recruited preferentially in both control and vagally blocked dogs during both ETL and hypercapnia. 3. The degree of recruitment of the abdominal muscles during ETL and hypercapnia in awake dogs is influenced by vagal feedback, but less so than in anaesthetized dogs. These results illustrate the importance of the vagi and abdominal muscle activation in load compensation. However, vagal reflexes are apparently not contributing to the preferential recruitment of the internal muscle layer. In awake dogs during vagal blockade abdominal muscle recruitment still occurs by extravagal mechanisms.

Role of vagal feedback from the lung in hypoxic-induced tachycardia in humans

We assessed the cardiovascular responses to systemic normocapnic hypoxia in five normal subjects, five double lung transplant patients with lung denervation and intact hearts, and five patients with denervated hearts. Progressive normocapnic hypoxia was induced over 10-15 min and maintained for 2-3 min each at 90, 87, 84, and 80% arterial O2 saturation (SaO2). Normal subjects showed the most pronounced mean increase in heart rate (dHR/dSaO2 = 0.86 +/- 0.13 beat/min per 1% SaO2). Three lung-denervated subjects had normal tachycardiac responses (1.6, 0.9, and 0.69 beats/min per 1%), whereas the other two had distinctly lower responses (0.34 and 0.39 beat/min per 1%). Most of the lung-denervated subjects also showed a significant tachycardia with even mild hypoxia; none showed a bradycardiac response to any level of hypoxia. In the heart-denervated group, hypoxic tachycardia was significantly lower than normal (0.29 +/- 0.13 beat/min per 1%). We conclude that vagal feedback from the lungs is not required for the normal chronotropic response to hypoxia in humans; however, this mechanism may contribute significantly to the marked variability in hypoxic-induced tachycardia found among human subjects. These data in humans contrast with the progressive bradycardiac response to hypoxia reported in vagally denervated (or nonhyperpneic) dogs and cats.

Vagal input enhances responsiveness of respiratory discharge to central changes in pH/CO2 in bullfrogs

This study investigated the interaction between vagal afferent input and central chemosensitivity in modulating the respiratory motor output of in vitro brain stem-spinal cord preparations from adult bullfrogs. With this preparation, the spatiotemporal distribution of respiratory-related motor output emulated that of intact bullfrogs; that is, the fictive breathing pattern was mostly episodic. Recordings from cranial motor nerves (V and X) showed that, without peripheral feedback, increasing the PCO2 of the mock cerebrospinal fluid (thereby reducing pH from 8.3 to 7.7) caused a modest increase in respiration-related burst frequency. When the pulmonary branch of a vagus nerve was stimulated phasically (2 V, 20 Hz, 0.2 ms) during each fictive breath to simulate afferent pulmonary stretch receptor feedback 1) the responsiveness of the preparation to the same changes in pH was augmented nearly threefold and 2) the breathing pattern remained episodic. It appears, therefore, that episodic breathing is an intrinsic property of the central nervous system in bullfrogs. It is concluded that there is a strong interaction between vagal feedback and central chemodetection in controlling the temporal relationships that characterize this episodic breathing pattern.

Apnoea following normocapnic mechanical ventilation in awake mammals: a demonstration of control system inertia.

1. Inhibition of inspiratory muscle activity from volume-related feedback during mechanical ventilation has been shown previously. To determine if this neuromechanical inhibition displays a memory effect, the duration of expiration immediately following cessation of mechanical ventilation was assessed in eight normal subjects. The subjects were passively mechanically ventilated via a nasal mask until the end-tidal CO2 (PET,CO2) was a minimum of 30 mmHg and inspiratory effort was no longer detected, as evidenced by stabilization of mouth pressure and disappearance of surface diaphragm EMG activity. The ventilator output was held constant at a mean tidal volume (VT) of 1.0 l and breath duration of 4.6 s and PET,CO2 was increased 1-1.5 mmHg/min (via increased inspired CO2 fraction, FI,CO2) until inspiratory muscle activity returned. The PET,CO2 at which activation first occurred was defined as the CO2 recruitment threshold (PCO2,RT). The mechanical ventilation protocol was repeated and the PET,CO2 increased 1-1.5 mmHg/min until it was a mean of 1.1 mmHg above spontaneous PET,CO2 and 3.6 mmHg below PCO2,RT. After 4-6 min of mildly hypercapnic mechanical ventilation, the mechanical ventilation was terminated. 2. Following termination of mechanical ventilation, the duration of the subsequent apnoea was 14.6 +/- 2.8 s (mean +/- S.E.M.) or 453 +/- 123% > spontaneous TE and 178 +/- 62% > the TE chosen by the subject during 'assist control' ventilation at VT = 1.0 l. 3. To test the hypothesis that the apnoea following cessation of mechanical ventilation was due to a vagally mediated memory effect, the study was repeated in five double-lung transplant patients with similar PCO2,RT to normal subjects. These pulmonary vagally denervated patients also displayed an apnoea (14.5 +/- 4.0 s) upon cessation of mechanical ventilation (at a PET,CO2 2.0 mmHg > eupnoea and 2.4 mmHg < PCO2,RT), that was 367 +/- 162% > spontaneous TE. 4. We also found significant apnoea in the awake dog immediately following mildly hypercapnic passive mechanical ventilation, and this was similar before and after bilateral vagal blockade (15.7 +/- 1.3 and 19.7 +/- 4.7 s, respectively). 5. We conclude that neuromechanical inhibition of inspiratory muscle activity, produced by passive mechanical ventilation at high VT, exhibits a memory effect reflected in TE prolongation, which persists in the face of substantial increases in chemoreceptor stimuli. This effect is not dependent on vagal feedback from lung receptors. 6. We hypothesize that this persistent apnoea represents an inherent 'inertia', characteristic of the ventilatory control system.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of tracheostomy on electrically induced vocalization in decerebrate cats

Electrical stimulation delivered to the rostral pons induced well coordinated activity of the intralaryngeal muscles and the ventilatory muscles for vocalization in unanesthetized, decerebrate cats. The stimulation reset the normal respiratory rhythm and induced vocalization with a newly developed rhythm. Continuous opening of the tracheostomy decreased the breathing cycle during induced vocalization. Opening of the prepared tracheostomy during vocalization caused a sudden decrease in the subglottic pressure, but the expiration phase was not abruptly terminated. These findings suggested that vagal feedback from pulmonary stretch receptors plays a more significant role in the maintenance of the breathing cycle during electrically induced vocalization than the laryngeal feedback from the laryngeal mucosa.

Respiratory modulation of muscle sympathetic nerve activity in intact and lung denervated humans.

We determined the influences of breathing-induced changes in intrathoracic and intravascular pressures, central respiratory drive, and pulmonary vagal feedback on the within-breath variation in skeletal muscle sympathetic nerve activity (MSNA) in humans. MSNA (peroneal microneurography), arterial blood pressure (Finapres finger monitor), and tidal volume (VT) were recorded continuously in six normal subjects and four heart-lung transplant patients during: 1) spontaneous air breathing; 2) increased FICO2; 3) voluntary augmentation of VT with and without inspiratory resistance; and 4) positive pressure, passive mechanical ventilation. During conditions 3 and 4, which were performed under isocapnic conditions with a high MSNA background (either high resting activity or nonhypotensive lower body suction), subjects breathed at control or elevated VT with normal or prolonged inspiratory time (TI); breathing frequency was 12 breaths per minute. During control breathing in normal subjects there was a distinct within-breath pattern of MSNA, with approximately 70% of the activity occurring during low lung volumes (initial half of inspiration and latter half of expiration). This within-breath variation of MSNA was potentiated with increased VT breathing (> 85% of activity occurring during low lung volumes; p < 0.05 versus control breathing) and was similar during the voluntary and CO2-induced hyperpneas. MSNA decreased progressively and markedly from onset to late inspiration; fell slightly further, reaching its nadir at end-inspiration/onset-expiration; and rose sharply during mid-late expiration. Only the nadir of MSNA was associated with any change in arterial pressure. Resistive breathing, especially at elevated VT, caused a fall in arterial pressure and increased respiratory drive during inspiration, yet MSNA still declined as lung volume increased. Normal within-breath modulation of MSNA also was observed during control and elevated VT induced via positive pressure with passive ventilation, which reversed lung inflation/deflation-induced intrathoracic pressure changes and reduced or removed respiratory motor output. During control breathing in transplant patients the specific within-breath pattern of MSNA was somewhat different than that of the normal subjects, but on average, the overall low lung volume to high lung volume MSNA ratio was similar to normal subjects. In contrast to the normal subjects, however, there was no potentiation of the within-breath variation of MSNA with elevated tidal breathing. These findings indicate that during normal levels of tidal breathing most of the respiratory phase influence on muscle sympathetic outflow observed in normal conscious humans is independent of baroreceptor-sensed fluctuations in intrathoracic or intravascular pressures and of lung inflation-stimulated vagal afferent activity.(ABSTRACT TRUNCATED AT 400 WORDS)

除脳ネコ脳幹電気刺激により誘発される発声時の内喉頭筋と呼吸筋活動の解析

Vocalization was induced by repetitive electrical stimulation (0.2ms, 25 to 80 μ A, 60 to 100Hz, lasting for 5 to 30 s) delivered to the brainstem (Horsley Clarke coordinates : A 1.5 to P 5.0, L or R 1.5 to 5.5, H -3.0 to -9.0) in unanesthetized pre-collicular-postmammilary decerebrate cats. During induced vocalization, the activities of both inspiratory (diaphragm) and expiratory (rectus abdominis) muscles were augmented. The stimulation also bilaterally augmented the activities of the abductor (posterior cricoarytenoid) and adductor (thyroarytenoid) muscles of the vocal folds during inspiration and expiration, respectively. The stimulation initiated in either inspiratory or expiratory phase reset the spontaneous respiratory rhythm. Following inspiration due to the activation of the diaphragm and abductor muscle of the vocal cords, expiration with vocalization and inspiration were alternately induced with a newly developed rhythm. This suggested that the tonic electrical stimulation delivered to the higher brainstem can alter rhythm generation of spontaneous respiration. Persistent opening of a T-tube inserted into the trachea decreased respiratory cycle. Although opening of the T-tube during vocalization decreased subglottic pressure, the expiratory phase did not abruptly terminated. It was suggested that the feedback input from the mechanoreceptors in the laryngeal mucosa was less important than the vagal feedback from the alveolar stretch receptors to maintain respiratory cycle during the induced vocalization.

Vagal modulation of respiratory muscle activity in awake dogs during exercise and hypercapnia.

Using chronically instrumented awake tracheotomized dogs, we examined the contributions of vagal feedback to respiratory muscle activities, both electrical and mechanical, during normoxic hypercapnia (inspired CO2 fraction = 0.03, 0.04, 0.05, and 0.06) and during mild treadmill exercise (3, 4.3, and 6.4 km/h). Cooling exteriorized vagal loops eliminated both phasic and tonic mechanoreceptor input during either of these hyperpneas. At a given chemical or locomotor stimulus, vagal cooling caused a further increase in costal, crural, parasternal, and rib cage expiratory (triangularis sterni) muscles. No further change in abdominal expiratory muscle activity occurred secondary to vagal cooling during these hyperpneas. However, removal of mechanoreceptor input during hypercapnia was not associated with consistent changes in end-expiratory lung volume, as measured by the He-N2 rebreathe technique. We conclude that during these hyperpneas 1) vagal input is not essential for augmentation of expiratory muscle activity and 2) decrements in abdominal expiratory muscle activity may be offset by increments in rib cage expiratory muscle activity and contribute to the regulation of end-expiratory lung volume.

Control of genioglossal muscle activity in the anesthetized piglet: the role of vagal afferents.

We examined genioglossal muscle electromyogram activity during room air breathing and hyperoxic hypercapnia in 10 anesthetized (halothane) newborn piglets before and after bilateral midcervical vagotomy. With vagal afferents intact, genioglossal activity was absent during room air breathing in 10/10 study animals and was recruited in only 4/10 piglets during carbon dioxide breathing. After vagotomy, genioglossal activity remained absent in 9/10 study animals during room air breathing but was recruited in 10/10 piglets during the hypercapnic gas exposure at arterial CO2 tensions comparable to prevagotomy levels. We conclude that vagal afferent feedback modulates genioglossal activity in anesthetized newborn piglets and exerts an inhibitory influence on the activity of this muscle during hyperpnea induced by carbon dioxide breathing.

Time-varying pulmonary arterial compliance

We tested the hypothesis that pulmonary arterial compliance (Ca) varies during the ventilatory cycle. Pressure and flow in the main pulmonary artery were measured in open-chest dogs under chloralose anesthesia (n = 12) with a positive-pressure volume-cycled ventilator. Input impedance was calculated from the pressure and flow waves of heart cycles obtained immediately after the start of inspiration (SI) and immediately after the start of expiration (SE). A lumped parameter model was used to calculate Ca from the input impedance spectrum of the main pulmonary artery. Three levels of positive end-expiratory pressure (PEEP) were used before and after meclofenamate (n = 6) or vagotomy (n = 6). Ca was significantly greater at SE than at SI at each level of PEEP. PEEP increased Ca at SE but not at SI. None of these changes was altered by meclofenamate or vagotomy, suggesting that these differences of Ca were due to passive mechanical effects rather than an active neurohumoral mechanisms. We conclude that Ca is time varying during the ventilatory cycle because it is altered by the dynamic increase of lung volume between SI and SE, but not with the quasi-static increase of lung volume induced by raising the level of PEEP. These changes of Ca were unaffected by vagal feedback or inhibition of cyclooxygenase. We suggest that the increased Ca just after the start of expiration may result from dynamic shifts of blood volume from the extra-alveolar to the alveolar vessels.