Central Inspiratory Activity Research Articles

Effect of bilateral destruction of the subretrofacial area on central inspiratory activity of the respiratory center and on the respiratory response to hypercapnia

Local bilateral destruction with 1 M glutamic acid of neuronal structures located between ventral surface of the medulla oblongata and the retrofacial nucleus (subretrofacial area) in rats increases the amplitude of pulses from the phrenic nerve and lowers respiratory rate. Hypercapnia does not affect the amplitude of phrenic nerve pulses but increases respiratory rate. It is suggested that the amplitude of central respiratory activity is regulated by the central chemoreceptors with participation of neuronal structures located in the subretrofacial area.

Breathing pattern during bronchial challenge in humans

Increases in minute ventilation (V'E) have been observed during exacerbations of asthma and in response to administration of histamine. However, it is not yet clear how the breathing pattern is affected, and whether the increase in V'E is found in general. In the present study, the effects of inhalation of histamine on respiratory frequency (fR), tidal volume (VT), V'E, and on functional residual capacity (FRC) were evaluated in 63 humans. Forty four subjects were hyperresponsive (BHR+). In each of these subjects, the doses of histamine applied for the present study (mean 3.5 mg x mL(-1)) caused a decrease in forced expiratory volume in one second (FEV1) that was greater than 20% of the control value. The dose of histamine applied in the 19 nonhyperresponsive subjects (BHR-) was substantially larger (8.0 mg x mL(-1)) whilst for this dose the decrease in FEV1 was less than 20% of control value. After histamine, fR was significantly increased in both subgroups of subjects, BHR+ and BHR-. The increase in V'E was significant in BHR- but not significant in BHR+. In general, the changes in V'E,fR and VT were not uniform; comparable numbers of subjects responded with increases (n=33) and decreases (n=30) in V'E. For fR 40 subjects responded with an increase and 23 with a decrease, and for VT these numbers were 26 and 37, respectively. The increase in FRC after histamine was significantly larger in BHR+ subjects than in BHR-. These findings may be interpreted to indicate that different mechanisms with opposite effects may be operating simultaneously, e.g. excitation of central inspiratory activity by stimulation of rapidly-adapting pulmonary stretch receptors, which will promote increases in respiratory frequency, tidal volume and minute ventilation, and bronchoconstriction with increased airway resistance, which will promote decreases in these parameters. As a consequence, depending on the net result of these opposite contributions to, e.g. minute ventilation, administration of histamine will cause an increase in minute ventilation in one subject and a decrease in another.

Modelling the peripheral chemosensory drive of ventilation on basis of homogenous sensory units.

Depth and timing of breath are supposed to be the result of the interaction of two functional compartments forming the respiratory pattern generator (“Inspiratory offswitch Hypothesis”). The first compartment generates the central inspiratory activity (CIA). The second one, the inspiratory off-switch (IO-S), has control of the inspiratory duration; when IO-S activity overpasses certain threshold the activity of the CIA is inhibited (Bradley et al, 1975; Cohen & Feldman, 1977; von Euler, 1977, 1986).

Mechanisms compensating for altered resistance to respiration during muscular exercise in man

Alterations in respiratory parameters following the substitution of a helium-oxygen (He−O2) or sulfur hexafluoride-oxygen (SF6−O2) mixture for air were analyzed during the first 10 respiratory cycles in human volunteers exposed to either of these mixtures for 3 min at rest and during forced respiration. Both at rest and during moderate physical exercise neither the volume of pulrnonary ventilation nor the partial carbon dioxide pressure differed significantly in the subjects breathing air, He−O2, or SF6−O2. When the He−O2 mixture was substituted for air, the forces developed by the inspiratory muscles, the work of breathing, the activity of the parasternal intercostal muscles, and the central inspiratory activity were all reduced, whereas substitution of the SF6−O2 mixture for air led to significant increases in these four parameters. It is concluded that compensatory responses of the respiratory system to altered density of the gaseous medium develop on the basis of the afferent impulse traffic from mechanoreceptors of the lungs and respiratory muscles and also on account of segmental reflexes and intrinsic properties of the muscle fibers themselves.

Generation of the respiratory rhythm: modelling the inspiratory off switch as a neural integrator

Neural integration is involved in the respiratory central processing of vagal afferent activity originating from lung mechanoreceptors. In the present work it is assumed that not only vagal activity, but also the incoming activities of the other inputs which converge into the “inspiratory off-switch”, are processed there by integration. Moreover, integration is considered to be essential for the inspiratory off-switch function. This assumption leads to a novel mathematical model, in which constancy of the inspiratory off-switch threshold and absence of a central inspiratory activity input to the inspiratory off-switch are postulated. The model accurately predicts the relationship between timing and depth of breathing measured experimentally under several steady-state conditions, including peripheral and central chemoreceptor stimulation, increased body temperature, increased elastic and flow resistive loads, and bilateral vagotomy. The model also provides adequate simulation of the integrative vagal processing and questions the idea that “accommodative” vagal processing originates from a separate process different to integration at the inspiratory off-switch. The assumption that integration is essential for the inspiratory off-switching suggests a simple basis for interpreting, electrophysiological properties of bulbo-pontine inspiratory neurons in terms of a neuronal circuit that acts like an integrator. The prediction of a new type of inspiratory neuron is discussed.

Breath‐by‐breath determination of inspiratory occlusion pressure

In order to determine the influence of breath-by-breath measurement of inspiratory occlusion pressure (P0.1) on the pulmonary ventilation, the respiratory timing and the central inspiratory activity as reflected by P0.1 per se, nine healthy males were studied as they breathed in a valve assembly including an externally controlled occlusion valve. A new technique was used, terminating occlusions at a preset inspiratory threshold pressure and determining P0.1 from linear regression of the mouth pressure curve. Subjects were studied at rest and during light exercise, with the occluding function (threshold pressure) on or off during alternating periods. Breath-by-breath variability of P0.1 was of the order of 30%. We found no detectable influence of breath-by-breath short-lasting inspiratory occlusions on tidal volume and ventilation. However, mean inspiratory flow was slightly increased due to a shortened inspiratory duration at rest and during light exercise. Also, raising the threshold pressure for occlusions from 69 to 147 Pa (0.7 to 1.5 cm H2O) resulted in a 20% increase of P0.1. We conclude that breath-by-breath measurement of P0.1 is a feasible technique, and that the slightly shortened inspiratory duration and the increased P0.1 with increased threshold pressure may not necessarily be expressions of a true stimulation of the central inspiratory activity.

Antagonistic interaction of laryngeal and central chemoreceptor respiratory reflexes.

Stimulation of laryngeal afferent fibers evokes a profound reflex inhibition of central respiratory drive. The interaction of this airway reflex with chemoreceptive ventilatory control mechanisms is poorly understood. The present study was undertaken to determine whether there is significant interaction between the effects of central chemoreceptor and laryngeal afferent stimulation on central inspiratory activity and, if so, to also determine the nature of the interaction. The effect of electrical stimulation of the superior laryngeal nerve (SLN) on the timing and intensity of central inspiratory activity was determined from the rectified and filtered phrenic neurogram in 10 dogs. Each dogs was decerebrated, artificially ventilated, vagotomized, and had the carotid bodies denervated. In each case, stimulation of the right SLN at 3 and 10 Hz caused a frequency-dependent slowing or arrest of central inspiratory activity. Increases in arterial PCO2 (PaCO2) attenuated the absolute level of inhibition of central inspiratory activity recorded during both SLN stimulation and control periods. Tp clarify the nature of the interaction between chemoreceptor and laryngeal afferent stimulation, the relationship between PaCO2 and central inspiratory activity was investigated during stimulation of the SLN at 0, 3, and 10 Hz. Control central inspiratory activity increased as a sigmoidal function of PaCO2. This sigmoidal relationship was greatly depressed during SLN stimulation but did not appear to be shifted along the PaCO2 axis. The results of this study therefore suggest that the interaction between central chemoreceptor and laryngeal afferent stimulation is multiplicative: the inhibition of the central inspiratory activity is mediated by an attenuation and not a resetting of central chemoreflexes.

Some reflex cardioinhibitory responses in the cat and their modulation by central inspiratory neuronal activity.

1. Cats were anaesthetized with a mixture of chloralose and urethane, and were artifically ventilated. 2. An open pneumothorax was provided by two large-bore tubes which were sealed in the sixth intercostal space on each side. They were connected to a Fleisch pneumotachograph. Phasic changes in central inspiratory neuronal activity were measured quantitatively as changes in the volume of the pneumothorax during temporary interruption of artificial respiration, the volume of the lungs being held constant at their end-expiratory level. In this way the activity of slowly adapting pulmonary stretch receptors was maintained constant. 3. Reflex cardioinhibitory responses were elicited by stimulation of (a) the carotid body chemoreceptors by intracarotid injections of cyanide; (b) the arterial baroreflex by controlled elevations of the blood pressure; (c) cardiac receptors by left atrial injections of veratridine; and (d) pulmonary C fibres (including J receptors) by right atrial injections of phenylbiguanide. 4. The effects of central inspiratory neuronal activity on pulse interval were assessed by comparing the values observed during the inspiratory and expiratory phases of the respiratory cycle in the control state and during stimulation of each cardiovascular receptor group. 5. The carotid chemoreceptor-induced bradycardia measured during the expiratory phase of respiration was reduced during inspiration to a value of about 15% of control. The central inspiratory drive was less effective in altering the reflex responses from the arterial baroreceptors and cardiac receptors, the corresponding values being 42 and 51% respectively. 6. In contrast, the bradycardia evoked by pulmonary C fibre stimulation was not significantly affected by the central inspiratory drive. 7. The differential nature of the modulation by the central inspiratory drive occurred independently of the integrity of the sympathetic nerve supply to the heart indicating that the cardiac efferents involved were largely fibres in the vagus nerves. 8. The possible explanation of these results in terms of central mechanisms is discussed.

Respiratory‐related discharge pattern of sympathetic nerve activity in the spontaneously hypertensive rat.

1. Synchronization of spontaneous sympathetic discharge during the respiratory cycle was studied in the cervical and renal nerves of vagotomized, normotensive Wistar-Kyoto rats (WKYs) and age-matched spontaneously hypertensive rats (SHRs). Phrenic nerve discharge was used as an index of central inspiratory activity. 2. In normotensive Wistar-Kyoto rats depression of sympathetic activity appeared at the onset of inspiration reaching a minimum at mid-inspiration. Peak maximal sympathetic discharge corresponded to postinspiratory phase; a second increase sometimes appeared in late expiration. Variations of respiratory frequency over wide range of experimental conditions by hypoxia, hyperoxia, hyper- or hypocapnia and transection of carotid sinus nerves did not affect this pattern. 3. In SHRs the respiratory-phase-related timing of sympathetic discharge was variable. In normoxia, the maximal sympathetic activity occurred in late inspiration, preceded by short depression at early inspiration and followed by postinspiratory depression. A second increase in sympathetic activity was observed in mid-expiration. 4. The pattern of respiratory phase modulated sympathetic activity in SHRs was altered by hypoxic stimulation of the peripheral chemoreceptors. The early inspiratory depression of sympathetic activity was substantially prolonged and the maximal sympathetic discharge was shifted from inspiration to early expiration. This effect was abolished after carotid sinus nerves had been cut. 5. Hypercapnic stimulation of central chemoreceptors in SHRs with carotid sinus nerves cut did not influence the timing of the sympathetic activity in relation to the respiratory phase, though the magnitude of rhythmical sympathetic discharges was increased. 6. We discuss the possibility that altered synchronization between central respiratory drive and sympathetic neuronal system may contribute to the neurogenic mechanisms of arterial hypertension in SHRs.

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

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

Stereotyped phrenic response to laryngeal afferent volleys: the mechanism and anesthetic sensitivity.

The stereotyped reflex changes in phrenic discharge, produced by train(s) of electrical shocks to myelinated afferents in the internal branch of the superior laryngeal nerve (SLN), were studied in vagotomized cats and rabbits, mechanically ventilated with the mixture of oxygen and nitrous oxide. Single weak shocks caused a short latency (4-5 msec) phrenic response, an excitation followed by a slight inhibition for 10 msec, which was repeatable at a rate of 200 Hz or more. Repeated weak shocks at a rate higher than 100 Hz or single stronger shocks caused a powerful inhibition with a limited duration (25-30 msec) of both the central inspiratory activity (CIA) and short latency response. This stereotyped inhibition, which was followed by a rebound excitation, could occur every 30-50 msec with some reduction and was apparently associated with a decreased slope of integrated phrenicogram. During inhalation of halothane (0.5-1.5%), the short latency phrenic response was reduced, while the stereotyped inhibition and the reduction of phrenic augmentation were markedly enhanced when the CIA was slightly depressed by halothane inhalation. Therefore, the stereotyped inhibition produced by myelinated laryngeal afferents.

Cardiovascular and respiratory responses evoked from the posterior cerebellar cortex and fastigial nucleus in the cat.

1. In both anaesthetized and decerebrate cats the cerebellar cortex (lobules VI, VII, VIII, IX and X) and the fastigial nucleus (f.n.) have been stimulated electrically, and chemically, while recording changes in phrenic nerve discharge, heart rate, arterial blood pressure and renal and femoral blood flow. 2. Stimulation of lobules VI, VII, VIII and Xb failed to elicit any cardiovascular or respiratory changes. Activation of lobule IX (the uvula), and in some preparations sub-lobule Xa, evoked cardiovascular and respiratory responses consistently. In the anaesthetized cat, electrical stimulation of the uvula evoked apnoea, a small bradycardia and a depressor response associated with vasodilatation in the hindlimb vascular bed. In contrast, stimulation in an equivalent region in a decerebrate preparation elicited an apneustic discharge, a pronounced tachycardia and a rise in arterial pressure with vasoconstriction in both renal and femoral vascular beds. In both the anaesthetized and decerebrate animals the pattern of response elicited by chemical activation was identical to that seen with electrical stimulation. 3. Electrical, or chemical, stimulation after administration of anaesthetic to the decerebrate cat then evoked an identical pattern of response to that seen in the 'intact' anaesthetized animal. This evidence suggests that the reversal in the pattern of the response in an effect of the anaesthetic agent and not the decerebration itself. 4. The only area of the f.n. to produce cardiovascular effects was the rostral region. Electrical stimulation of the rostral f.n. in both anaesthetized and decerebrate preparations inhibited central inspiratory activity and evoked tachycardia, along with a pressor response associated with vasoconstriction in both renal and femoral vascular beds. In contrast, chemical excitation of those sites in the rostral f.n. shown previously to produce pronounced cardiovascular and respiratory changes failed to elicit any changes in the recorded variables. 5. The present evidence suggests that there are two areas in the cat cerebellum which can exert pronounced cardiovascular and respiratory effects. The patterns of response elicited by electrical stimulation of the posterior cortex and rostral f.n. are mediated by two separate cerebellar-brainstem pathways as judged by the two different effects of anaesthesia on the evoked responses. We suggest that the f.n. may not play a role in the control of the cardiovascular system since chemical excitation of cell bodies of the rostral f.n. failed to elicit the so-called 'fastigial pressor response'.

Interactive effects of CO2 and upper airway negative pressure on breathing pattern.

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

Reflex cardiorespiratory responses to pulmonary vascular congestion.

The purpose of these studies was to determine the reflex responses of the cardiovascular system and central inspiratory activity caused by pulmonary vascular congestion. We used a canine preparation in which the left lung was isolated in situ and could be exposed to a variety of stimuli, including distension of the pulmonary capillaries with blood, without direct mechanical or chemical alterations on the circulation. We found that lung expansion to 30 cmH2O and stimulation of nerve endings of the left lung with capsaicin caused pronounced transient reflex bradycardia (-30 to -50 beats/min) and hypotension (-25 to -40 mmHg) and caused reflex cessation of inspiratory activity. Pressurizing the left pulmonary vessels by injecting blood in volumes sufficient to raise pulmonary transcapillary pressures to 30 mmHg caused no changes in heart rate, systemic arterial pressure, or inspiratory muscle activity. These results lead us to conclude that pulmonary vascular congestion does not stimulate pulmonary C-fibers or any other nerve endings to such a degree as to cause detectable changes in blood pressure, heart rate, or central inspiratory activity. Morphometric analysis revealed distended capillaries engorged with blood, but the alveolar wall surface area was not increased which raises the possibility that expansion of the alveolar membrane may be needed to mechanically initiate the C-fiber reflex.

Respiratory drive during sudden cold water immersion

Sudden decreases in cutaneous temperature induce an immediate ventilatory response, which has been termed the inspiratory or ‘gasp’ reflex. This respiratory response has been implicated as a contributing factor to cold water immersion drowning. In the present study, five subjects wearing either shorts or a variety of thermal protective apparel were immersed on separate occasions in 10 °C water. The observed peak mean skin temperature cooling rates (dT̄s/dt) for the different conditions varied from 6.9 ± 2.1 °C/min for the shorts condition to 1.8 ± 0.3 °C/min for a helicopter pilot suit made of cotton ventile material. During the immersion, recordings were made of respiratory drive, as indicated by the mouth occlusion pressure at 100 msec following the onset of inspiration (P 0.1). The respiratory drive, an indicator of central inspiratory activity, correlated well with peak dT̄s/dt. The slope P 0.1/(dT̄s/dt) was subject dependent and did not appear to be related to body composition. The substantial intersubject variability in the respiratory response is suggested to result from differences in the central integration of thermoafferent information. It is concluded that the inspiratory reflex is the result of cutaneous thermoreceptor activity.

Changes in inspiratory activity after injection of adenosine and hypoxanthine in cats.

The effects of intra-arterial and intravenous injections of adenosine and hypoxanthine were investigated with special reference to respiratory variables in anesthetized young cats. Studies were made of the effects on inspiratory activity (phrenic nerve activity), heart rate, blood pressure and central venous pressure. To assess the risk of accumulation of adenosine degeneration products after several injections measurements were also made of hypoxanthine, xanthine and urate in plasma at intervals after the injections. It was found that intra-arterial and intravenous injections of adenosine increased central inspiratory activity during the first few breaths after the injection. The blood pressure and heart rate decreased slightly and central venous pressure increased slightly after the injection. Degradation of adenosine and its metabolites takes place rapidly and it is therefore unlikely that metabolites influence the results. It is concluded that adenosine causes brief stimulation of inspiratory activity.

Inhibition of phrenic nerve activity during positive‐pressure ventilation at high and low frequencies

A study was made to determine whether the ventilatory pattern, in terms of ventilatory frequency, insufflation period and end-expiratory pressure, influences the arterial blood gas level at which central inspiratory activity is inhibited, and whether further expansion of the lung changes this activity. This was accomplished by measuring arterial pH and blood gases, and intratracheal, intrapleural and transpulmonary pressures, at the setting of positive-pressure ventilation causing inhibition of phrenic nerve activity in chloralose-anaesthetized cats. Spontaneous breathing movements were prevented by muscle relaxation. Ventilatory frequencies of 15-120 breaths per minute (b.p.m.) were studied at at least two different insufflation times. A volume-controlled ventilator with a large compressible volume was used in the frequency range 15-45 b.p.m. and a constant flow respirator with a low-compressible volume in the range 45-120 b.p.m. A much lower PCO2 was needed for phrenic nerve activity to be inhibited at a ventilatory frequency of 15 b.p.m. than at higher frequencies. At ventilatory frequencies between 30 and 120 b.p.m. inhibition could be achieved at a higher PCO2, within the normal range. The inhibition of phrenic nerve activity tended to be less stable when PEEP was added during ventilation with a long insufflation period, but PEEP did not influence the arterial blood gas level at which inhibition occurred. In the lower frequency range of 15-30 b.p.m., inspiratory activity was observed with bursts at the same rate as the insufflations given by the ventilator. The intratracheal peak pressures at ventilation causing inhibition of phrenic nerve activity decreased with increasing ventilatory frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)

Ventilatory recovery from hypothermia in anesthetized cats

Ventilation and breathing pattern were recorded in a group of seven anesthetized cats during rewarming from 24 to 38°C of esophageal temperature. It was found that at 24°C, ventilation was very much depressed accounting for an alveolar hypoventilation resulting in hypoxia and hypercapnia. During rewarming, ventilation increased steadily; this was caused by sequential changes in central inspiratory activity (V T/Ti) and Ti/Tt ratio reflecting breath timing. Changes in V T/Ti have been initially attributed to an improvement in chemoresponsiveness and subsequently, to an involvement of supra-pontine thermoregulatory control areas during rewarming. Marked changes in breath timing, especially observed between 28 and 34°C, have been attributed to a direct effect of rewarming upon the brain stem respiratory network. It has the result, that during hypothermia, several components of the respiratory control system are differently affected causing marked changes in breathing pattern and ventilation. They are accompanied by modifications in arterial blood pressure and heart rate.

Respiratory arrhythmias and airway CO2, lung receptors, and central inspiratory activity.

The purpose of this study was to determine whether hypocapnia affects heart rate secondary to an effect on pulmonary receptors. Dogs were anesthetized and placed on cardiopulmonary bypass. Interrelationships among airway CO2, central inspiratory activity, and lung receptor effects on respiratory-related heart rate changes (respiratory arrhythmias) were studied after vagal efferent activity was increased secondary to baroreceptor stimulation. Hypocapnia, isolated to the lungs, produced an increase in the magnitude of the respiratory arrhythmias observed. Two mechanisms may produce these results. Hypocapnia affects pulmonary receptors, which 1) reflexly alter heart rate and 2) modulate breathing frequency, thus altering the dynamics of the respiratory arrhythmias that were produced. The results also suggested that the reflex increase in heart rate in response to lung inflation and the Hering-Breuer expiratory-facilitatory reflex are either produced by different pulmonary receptors or by the same pulmonary receptors but may be mediated by different central mechanisms.

Reflex effects on breathing of laryngeal denervation, negative pressure and SO 2 in upper airways

Respiratory reflex effects of laryngeal denervation, negative pressure and SO 2 in upper airways were studied in anesthetized rabbits. (a) Inspiratory efforts with nasal occlusion had longer duration (T io) and smaller diaphragm activity (Adi) than with tracheal occlusion.After secretion of superior laryngeal nerves (SLN) these differences disappeared: values with tracheal occlusion became similar to those with nasal occlusion before denervation. This suggests that laryngeal pressure receptors, firing at zero pressure and decreasing their discharge with negative pressures, increase central inspiratory activity. (b) After SO 2 T io, both with tracheal and nasal occlusion, increased even after laryngeal denervation, provided SO 2 flowed through nasa pathway. Hence, nose and/or rhinopharynx contain receptors affected by SO 2. (c) After laryngeal denervation and S 2 T io was shorter with nasal than with tracheal occlusion, despite equal Adi. This, combined with the above findings, suggests two groups of pressure receptors in nose and/or rhinopharynx with opposite effects on inspiratory off-switch: one unaffected and the other probably blocked by SO 2. (d) During nose breathing section of SLN produced only a slight decrease in mean inspiratory flow.