Intralaryngeal CO2 Research Articles

Effects of intralaryngeal carbon dioxide and acetazolamide on the laryngeal chemoreflex.

Sudden infant death syndrome is the leading cause of death in infants in the United States. The laryngeal chemoreflex (LCR) is thought to contribute to its pathogenesis. In adult animals, increasing levels of intralaryngeal CO2 result in a decrease in ventilatory activity. Intravenous acetazolamide (AZ) abolishes this response. The purpose of this study was to determine the effects of intralaryngeal CO2 and AZ on the LCR and respiratory physiology of piglets under normoxic and hypoxic conditions. We applied 0% or 10% CO2 in a randomized order to the larynx of 26 piglets. Intubation via tracheotomy prevented inhalation of the gas mixtures. Laryngeal stimulation was performed under normoxic conditions (PaO2 of >70 mm Hg) in 15 animals and under hypoxic conditions (PaO2 of 50 to 65 mm Hg) in 11 animals both with and without intravenous AZ (5 mg/kg). Respiratory and cardiovascular response data were recorded. Ten percent intralaryngeal CO2 has no significant effect on mean baseline respiratory rate, systemic PaCO2 or PaO2 levels, or apnea duration (p > .05). The use of AZ (versus no AZ) resulted in significantly higher baseline respiratory rates (64 versus 51 breaths per minute; p = .016), a decreased baseline systemic PaCO2 level (38.8 versus 45.9 mm Hg; p < .001), a higher baseline PaO2 level (97.9 versus 82.8 mm Hg; p < .001), shorter mean apnea durations (15.5 versus 24.8 seconds; p = .001), a higher lowest O2 saturation level after the stimulus (78.0% versus 68.4%; p = .003), and fewer profound apneas (10 of 90 versus 41 of 90 trials; p < .001). We conclude that 10% intralaryngeal CO2 does not decrease ventilatory activity in piglets and has no significant effect on the LCR. Acetazolamide, however, appears to have a protective effect against the LCR, resulting in shorter and less severe apneas. The protective effect of AZ against the LCR appears to be related to its ability to stimulate the respiratory drive and increase oxygenation at baseline.

Effects of CO2 and H+ on laryngeal receptor activity in the perfused larynx in anaesthetized cats.

1. Intralaryngeal CO2 reflexly decreases ventilation and increases upper airway muscle activity. Topical anaesthesia of the laryngeal mucosa or cutting the superior laryngeal nerves (SLNs) abolishes these reflexes, indicating that the receptors responsible are superficially located and that their afferent fibres are in the SLN. Intralaryngeal CO2 affects the activity of receptors recorded from the SLN. 2. An isolated, luminally perfused laryngeal preparation was developed in anaesthetized, paralysed cats in order to compare the effects of solutions with varying levels of pH and PCO2 on pressure-sensitive laryngeal receptor activity. Since the pH of tracheal surface fluid is reported to be approximately 7.0, two neutral (pH 7.4 and 7.0) and two acidic (pH 6.8 and 6.3) solutions were used. 3. Compared with neutral acapnic control solutions, neutral hypercapnic (PCO2 64 mmHg) solutions either excited or inhibited the discharge of 113 out of 211 pressure-sensitive SLN afferents. In 24 receptors, the effects of hypercapnic solutions with either neutral or acidic pH were similar in both direction and magnitude. In 50 receptors affected by neutral hypercapnic solutions, acidic acapnic solutions had no effect on 66 % of units and significantly smaller effects in the remaining units. In 17 receptors, the effects of neutral solutions with a PCO2 of 35 mmHg were significantly less than for neutral solution with a PCO2 of 64 mmHg. 4. These results show that the effects of CO2 on laryngeal pressure-sensitive receptors are independent of the pH of the perfusing media, and suggest that acidification of the receptor cell or its microenvironment is the main mechanism of CO2 chemoreception.

Intralaryngeal CO2 reduces the inspiratory drive in cats by sensory feedback from the larynx.

Larynx is a powerful reflexogenic area in regulation of breathing. Majority of the respiratory responses from the laryngeal airway is defensive, hypoventilatory in function. As a part of the dead space larynx is exposed to carbon dioxide (CO2) during each expiration. It has been shown that intralaryngeal CO2 in animal preparation elicits a decrease in ventilation (6). This effect has a sensory pathway in the superior laryngeal nerve. Most fruitful recent search for the CO2 - responsive receptors within the laryngeal passage did not reveal any specialized endings. Few receptors are stimulated by intralaryngeal CO2 (1, 7), while activity of the remaining ones is attenuated (4). This decreased afferent input from the laryngeal airway might well contribute to changes in the respiratory pattern induced by excess of CO2. We reasoned that overall increased ventilation evoked by the inhaled CO2 is attenuated by the laryngeal inhibitory input. The present experiments were designed to study the effects of increased concentration of carbon dioxide in the functionally separated laryngeal airway on respiratory pattern and to assess the role of vagal and sensory laryngeal feedback in this respiratory response.

Influence of intralaryngeal CO2 on the response of laryngeal afferents to upper airway negative pressure.

Effects of intralaryngeal CO2 on the response of superior laryngeal afferents to negative pressure were investigated in 20 anesthetized spontaneously breathing adult cats. Single-fiber action potentials were recorded from the peripheral cut end of the superior laryngeal nerve. The larynx was exposed to negative pressure during inspiration when the animal breathed against an occluded upper airway. Among the 99 receptors evaluated, 54 were respiratory modulated and 45 were nonmodulated endings. The effect of intralaryngeal CO2 on the response of 39 receptors responding to negative pressure was determined by exposure of the larynx to CO2 or air for 1 min followed immediately by upper airway occlusion. The mean discharge frequency of 22 fibers inhibited by negative pressure was 32.4 +/- 2.6 Hz during air trials compared with 29.9 +/- 2.6 Hz during CO2 trials (P < 0.005). During occlusion of the upper airway after the warm humidified air trial, the discharge frequency of these endings decreased to 24.2 +/- 2.3 Hz compared with 17.5 +/- 2.2 Hz after CO2 trial (P < 0.001). The mean discharge frequencies of 17 fibers stimulated by negative pressure were 3.7 +/- 2.6 and 4.4 +/- 1.8 Hz, respectively, during air and CO2 trials. The mean frequencies increased to 14.7 +/- 3.5 Hz (air) and 18.6 +/- 4.0 Hz (CO2) during upper airway occlusions (P < 0.01). We conclude that intralaryngeal CO2 can alter the response of pressure-sensitive laryngeal afferents, thereby having a role in the maintenance of upper airway patency.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of intralaryngeal CO2 and H+ on laryngeal receptor activity in the perfused larynx in cats.

Intralaryngeal CO2 alters discharges of superior laryngeal nerve (SLN) afferent fibres (Boushey et al, 1974. Bradford et al, 1990) and reflexly enhances the activity of upper airway dilating muscles (Nolan et al, 1990, Bartlett et al, 1992a), decreases ventilation (Boushey et al, 1974, Nolan et al, 1990) and phrenic nerve activity (Bartlett et al, 1992a) These reflex effects are abolished by SLN section. The above results suggest that laryngeal CO2 receptors may play an important role in maintaining upper airway patency To elucidate mechanisms of CO2-induced effects on laryngeal mechanoreceptors, an in situ, isolated, perfused larynx has been developed Part of this study has been briefly reported elsewhere (O’Regan et al, 1993)KeywordsTest SolutionNegative PressurePositive PressurePhrenic NerveControl SolutionThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Alteration of ventilatory activity by intralaryngeal CO2 in the cat.

1. We investigated the responses of phrenic and hypoglossal nerve activities to the addition of 3, 5 and 10% CO2 to a constant flow of warm, humidified air through the isolated upper airway in decerebrate, paralysed, artificially ventilated cats. 2. In bilaterally vagotomized animals, intralaryngeal CO2 caused a dose-related decrease in peak integrated phrenic activity. This response became attenuated with time, but was still discernible after 3 min of continuous intralaryngeal CO2. In the same experiments, intralaryngeal CO2 caused a gradual increase in peak integrated hypoglossal nerve activity. 3. Intermittent pulsing of intralaryngeal CO2 during neural inspiration or expiration resulted in similar, but smaller decreases in the phrenic activity of some animals. Hypoglossal activity was not influenced appreciably by this procedure. 4. Systemic hypercapnia attenuated the phrenic responses to intralaryngeal CO2. The hypoglossal responses were greatly reduced or abolished. 5. In vagally intact cats, ventilated by a servo-respirator in accordance with phrenic nerve activity, intralaryngeal CO2 resulted in only a trace of reduction in phrenic discharge. After bilateral vagotomy, the same animals showed typical responses, as described above. 6. All responses to intralaryngeal CO2 were abolished after bilateral section of the superior laryngeal nerves (SLNs). 7. We conclude that intralaryngeal CO2 acts by way of receptors with afferents in the SLNs to decrease phrenic and increase hypoglossal nerve activities. The responses are not importantly gated during neural inspiration or expiration. The responses to intralaryngeal CO2 are most clearly demonstrable after bilateral vagotomy, suggesting that vagal mechanisms serve to stabilize respiratory motor neural activity in intact animals.

Responses of laryngeal receptors to intralaryngeal CO2 in the cat.

1. We recorded afferent activities of single fibres in the superior laryngeal nerves of decerebrate or anaesthetized, paralysed cats while 3, 5 and 10% CO2 was added to a constant flow of warm, humidified air through the isolated upper airway. 2. Fifty-three receptors with discharge frequencies modulated by intralaryngeal CO2 were studied. Of these, forty-eight showed CO2-induced attenuation of their firing rates. Pulses of 3, 5 or 10% CO2, alternating with air at intervals ranging from 1.5 to 60 s, also diminished the discharge frequencies. This diminution was greater with higher CO2 concentrations and longer pulse durations. 3. Five of the fifty-three receptors were stimulated by intralaryngeal CO2. The discharge frequencies of these units increased slowly and by only a few impulses per second during CO2 exposure. 4. Thirty-four of the CO2-sensitive receptors were tested with other stimuli, including water, saline, positive and negative intralaryngeal pressures and cold air. The responses to these stimuli varied among receptors, but many of the units that reduced their frequencies with intralaryngeal CO2 were consistently stimulated by positive and/or negative intralaryngeal pressures. 5. Thirty-six of the receptors were anatomically located by probing the upper airway. Twenty-six were in the larynx, and ten were in the rostral trachea, within 5 mm of the cricoid cartilage. 6. The results, which are directly applicable to the investigation of reflex responses reported in the preceding paper, indicate that the predominant initial response to intralaryngeal CO2 under the conditions of these studies is attenuation of laryngeal receptor activity.

The effects of changes in laryngeal airway CO2 concentration on genioglossus muscle activity in the anaesthetized cat

In the anaesthetized cat the larynx was isolated in situ, artificially ventilated and used to assess reflex effects exerted by respiration-related laryngeal stimuli on genioglossus electromyographic activity (Gg EMG) and respiratory frequency (RF). Phasic Gg EMG was not observed when the larynx was unventilated but was evoked, with a concurrent decrease in RF, when negative pressures or oscillatory pressures similar to those of normal ventilation were applied to the larynx. Increases in laryngeal airway CO2 concentration also enhanced Gg EMG and reduced RF. All reflex effects were abolished by bilateral section of the superior laryngeal nerves. We propose that negative intralaryngeal pressure and CO2 may act together to restore pharyngeal patency during obstructive apnoea.