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Biomedical subjects

S L Knuth

Publications and source records attributed to S L Knuth.

12 recordsLinked to original sources

Phrenic and hypoglossal neural responses to cold airflow in the upper airway.

Cold air flowing through the larynx is known to alter the activities of laryngeal receptors with afferents in the superior laryngeal nerves (SLNs) and to induce reflex apnea in neonatal mammals. To examine the ventilatory response in adult animals and to explore associated upper airway motor responses, we recorded phrenic and hypoglossal neural responses to cooling the isolated larynx with cold air in decerebrate, vagotomized, paralyzed, ventilated cats. The most consistent response was phrenic inhibition, which occurred in all animals tested. Either excitation or inhibition of hypoglossal activity was seen consistently in individual cats, with the result that the group response was not statistically significant. All responses to laryngeal cooling were abolished by section of the SLNs. The findings confirm that directing cold air through the larynx causes reflex inhibition of ventilatory (phrenic) activity, but raise new questions as to how the two, directionally opposite hypoglossal responses are mediated.

Animals

Influence of laryngeal CO2 on respiratory activities of motor nerves to accessory muscles.

Intralaryngeal CO2 in decerebrate, vagotomized cats decreases phrenic nerve activity and increases the respiratory activity of the hypoglossal (HG) nerve. These responses are mediated by afferents in the superior laryngeal nerves. To explore the responses of other respiratory motor nerves to this stimulus, we have recorded the activities of the nasolabial (NL) branch of the facial nerve, the posterior cricoarytenoid (PCA) and thyroarytenoid (TA) branches of the recurrent laryngeal nerve and the nerve to triangularis sterni (TS) muscle. In response to 5 and 10% CO2 in the surgically isolated upper airway, we found dose-related decreases in phrenic activity, increases in HG and NL activity and characteristic, but intermittent, exaggeration of early expiratory bursts of TA activity. The activities of the PCA and TS nerves showed no consistent responses. These results broaden the definition of the reflex response to intralaryngeal CO2, revealing components that reflect ventilatory inhibition, upper airway dilation and laryngeal protection.

Animals

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.

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.

Animals

Dependence of pharyngeal resistance on genioglossal EMG activity, nasal resistance, and airflow.

We investigated the quantitative relationships among pharyngeal resistance (Rph), genioglossal electromyographic (EMGge) activity, nasal resistance (Rna), and airflow in 11 normal men aged 19-50 while they were awake. We made measurements with subjects seated with the head erect, seated with the head flexed forward approximately 40 degrees, and supine. Each subject wore a face mask connected to a pneumotachograph to measure airflow. After topical anesthesia of the nose, two catheters for measuring nasal and pharyngeal airway pressures were passed through one nostril: the nasal pressure catheter was positioned at the nasal choanae, and the pharyngeal pressure catheter was positioned just above the epiglottis. We measured EMGge activity with an intraoral surface electrode. The subjects breathed exclusively through the nose while inhaling room air or rebreathing CO2. We measured Rph, Rna, airflow, and EMGge activity at approximately 90-ms intervals throughout each inspiration. Rph was invariant as head position was changed. At any given head position, EMGge activity rose as airflow increased, and Rph remained constant. In contrast, Rna increased as airflow increased. Because Rph was constant, EMGge activity was not correlated with Rph, but EMGge was positively correlated with Rna and airflow. On the basis of the stability of Rph in the face of marked changes in collapsing forces, we conclude that the dynamic interplay of posture, head and jaw position, and upper airway muscle activity quite effectively maintains pharyngeal patency, and interactions among these factors are subtle and complex.

Adult

Reflex inhibition of crural diaphragmatic activity by esophageal distention in cats.

Distention of the esophagus has been shown to result in selective inhibition of phasic inspiratory activity in the crural portion of the diaphragm, with no effect on costal diaphragmatic activity. The purpose of this study was to determine rigourously the afferent pathways that mediate this response. Bipolar EMG electrodes were placed in the costal and crural portions of the diaphragm in decerebrate, spontaneously breathing cats. Distention of the esophagus by inflation of a Foley catheter balloon with 20 ml of air resulted in a selective inhibition of crural hiatal EMG activity, while costal EMG activity was maintained at predistention levels. The distention was accompanied by a reduction in respiratory frequency. Transection of the spinal cord at the C8-T1 level did not obliterate the crural inhibition produced by inflation. Section of the C4-C8 dorsal roots also failed to abolish the response. However, after bilateral cervical vagotomy, esophageal distention no longer influenced diaphragmatic EMG activity. These results indicate that the crural inhibition observed with esophageal distention is vagally mediated and is not influenced importantly by intercostal or phrenic afferents. Records of activity of the phrenic nerve branch innervating the crural portion of the diaphragm showed a similar response pattern, confirming that the inhibition is central in origin and that the crural fibers inhibited by distention are only a fraction of the total population of crural phrenic motoneurons.

Animals

Patterns of neural and muscular electrical activity in costal and crural portions of the diaphragm.

To determine whether the central respiratory drives to costal and crural portions of the diaphragm differ from each other in response to chemical and mechanical feedbacks, activities of costal and crural branches of the phrenic nerve were recorded in decerebrate paralyzed cats, studied either with vagi intact and servo-ventilated in accordance with their phrenic nerve activity or vagotomized and ventilated conventionally. Costal and crural electromyograms (EMGs) were recorded in decerebrate spontaneously breathing cats. Hypercapnia and hypoxia resulted in significant increases in peak integrated costal, crural, and whole phrenic nerve activities when the vagi were either intact or cut. However, there were no consistent differences between costal and crural neural responses. Left crural EMG activity was increased significantly more than left costal EMG activity in response to hypercapnia and hypoxia. These results indicate that the central neural inputs to costal and crural portions of the diaphragm are similar in eupnea and in response to chemical and mechanical feedback in decerebrate paralyzed cats. The observed differences in EMG activities in spontaneously breathing animals must arise from modulation of central respiratory activity by mechanoreceptor feedback from respiratory muscles, likely the diaphragm itself.

Animals

Diaphragmatic electromyography using a multiple electrode array.

We have developed a new technique for diaphragmatic electromyography using an array of seven sequential electrode pairs at 1.0-cm spacing on an esophageal catheter. This array provides information about the spatial distribution of the electrical field generated by the diaphragm and reveals a sharply peaked variation of electrical potential with distance along the esophagus. The rectified and integrated information from each of the seven pairs is summed to give an approximation to the total electrical activity over the span of the array, providing a signal that is relatively insensitive to the position of the array over approximately 4 cm of catheter movement and removes the requirement for balloon stabilization of the catheter. With our array, we have confirmed the artifact in the evoked compound muscle action potential that seems to be related to diaphragmatic shape as reported by others who used supramaximal phrenic nerve stimulation, but the magnitude of this artifact (compared with the functional residual capacity level) was modest near functional residual capacity, averaging 12 +/- 14% (SD) for lung volumes 1.0 l above and -4 +/- 15% for lung volumes 1.0 l below functional residual capacity along the rib cage-abdomen relaxation line.

Action Potentials

Influence of extreme hypercapnia on respiratory motor nerve activity in cats.

Sedative drugs have been found to depress the respiratory activity of upper airway muscles more than that of the diaphragm. To determine whether CO2 at narcotic levels has a similar action, we recorded phrenic and hypoglossal nerve activities in decerebrate, vagotomized, paralyzed cats. T5 or T6 external intercostal nerve activity was also recorded in some animals. End-tidal CO2 concentration was raised progressively to over 30% or until depression of nerve activity was apparent. Respiratory frequency was reduced by severe hypercapnia in most cats. Hypoglossal nerve activity was consistently decreased more than that of the phrenic nerve. In most cases intercostal nerve activity was also more susceptible than phrenic nerve activity to hypercapnic depression. The results indicate that CO2 at narcotic levels interferes both with the central pattern generator for breathing movements and with the expression of the pattern in specific motor nerves.

Animals

Hypoxia inhibits abdominal expiratory nerve activity.

Our purpose was to examine the influence of steady-state changes in chemical stimuli, as well as discrete peripheral chemoreceptor stimulation, on abdominal expiratory motor activity. In decerebrate, paralyzed, vagotomized, and ventilated cats that had bilateral pneumothoraces, we recorded efferent activity from a phrenic nerve and from an abdominal nerve (cranial iliohypogastric nerve, L1). All cats showed phasic expiratory abdominal nerve discharge at normocapnia [end-tidal PCO2 38 +/- 2 Torr], but small doses (2-6 mg/kg) of pentobarbital sodium markedly depressed this activity. Hyperoxic hypercapnia consistently enhanced abdominal expiratory activity and shortened the burst duration. Isocapnic hypoxia caused inhibition of abdominal nerve discharge in 11 of 13 cats. Carotid sinus nerve denervation (3 cats) exacerbated the hypoxic depression of abdominal nerve activity and depressed phrenic motor output. Stimulation of peripheral chemoreceptors with NaCN increased abdominal nerve discharge in 7 of 10 cats, although 2 cats exhibited marked inhibition. Four cats with intact neuraxis, but anesthetized with ketamine, yielded qualitatively similar results. We conclude that when cats are subjected to steady-state chemical stimuli in isolation (no interference from proprioceptive inputs), hypercapnia potentiates, but hypoxia attenuates, abdominal expiratory nerve activity. Mechanisms to explain the selective inhibition of expiratory motor activity by hypoxia are proposed, and physiological implications are discussed.

Abdomen

Differential depression of hypoglossal nerve activity by alcohol. Protection by pretreatment with medroxyprogesterone acetate.

Upper airway obstruction during sleep occurs more commonly in men than in women and has been treated with progestational agents with some success. Alcohol ingestion exacerbates sleep apnea, and recent studies have established that alcohol depresses the respiratory motor activity to upper airway muscles more than that to the diaphragm, a response pattern that favors upper airway obstruction during inspiration. To investigate the possibility that progesterone provides some protection from this action of alcohol, we studied the responses of phrenic and hypoglossal nerve activities to alcohol infusion in decerebrate cats pretreated with medroxyprogesterone acetate (MPA) or with control injections. The results indicate that pretreatment with MPA reduces the alcohol-induced mismatching of hypoglossal and phrenic activities. This action of MPA may contribute to its effectiveness in the treatment of some patients with inspiratory obstruction during sleep.

Action Potentials