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Biomedical subjects

N S Cherniack

Publications and source records attributed to N S Cherniack.

At least 163 records · Page 9Linked to original sources

The effects of hypercapnia and hypoxia on single hypoglossal nerve fiber activity.

The respiratory related modulation of hypoglossal nerve activity has been studied at the single fiber level in cats under hyperoxic hypercapnia and hypoxic conditions and their conduction velocities determined. Changes in fiber activity were compared to simultaneous changes occurring in phrenic activity. Three different kinds of discharge patterns were observed: (a) inspiratory, (b) phasic activity during both inspiration and expiration, and (c) continuous random activity with no respiratory modulation. These fibers could be grouped into three categories according to their pattern of discharge during CO2 breathing. Type I fibers, mean conduction velocity of 30.0 m/sec, exhibited only an inspiratory phasic discharge during 100% O2 breathing. Their discharge frequency increased rapidly with higher levels of CO2 and hypoxia. Type II fibers, mean conduction velocity of 36.7 m/sec, had three different kinds of inspiratory-expiratory discharge patterns during 100% O2 breathing. With increasing hypercapnia or hypoxia fibers of this group discharged phasically during inspiration and discharge at low frequency during expiration. Type III fibers had a non phasic discharge pattern at 100% O2 breathing and at all levels of CO2 tested (up to 10%). Discharge frequency rose during CO2 rebreathing and hypoxia, but the rate of increase was much less than Type I and Type II fibers. Their mean conduction velocity was 41.3 m/sec. The inspiratory activity of Type I and II fibers increased their activity more than the phrenic during hypercapnia and hypoxia. Type II and Type III fibers are responsible at least in part for the tonic activity of the nerve.

Animals↗

Effects of aging on sensation of respiratory force and displacement.

The psychophysical technique of magnitude production was used to evaluate the sensation of inspiratory force and inspired volume in young and older subjects. Inspiratory force was generated during a static inspiratory maneuver against a closed airway. The exponent of the power function relationship between airway pressure and sensation intensity during force scaling was not significantly different between young and older subjects. In contrast, the exponents for the magnitude production of inspired volume were significantly greater in the older compared with the young group. We also assessed the effects of age on the relative importance of force and displacement signals on the sensation of inspired volume. Subjects attempted to reproduce a control tidal volume while breathing against a series of inspiratory resistive and elastic loads. In both groups error in tidal volume reproduction increased progressively as the severity of the load increased. During moderate and severe loading the error in the older subjects was significantly greater than in the young group. Correspondingly, the peak inspiratory airway pressures at tidal volume reproduction against these loads were significantly smaller in the older compared with the young subjects. The results suggest that in older subjects cues related to respiratory muscle force are more important than volume in the sensation of lung volume changes. In young subjects the sensation of lung volume changes is based to a greater degree on signals of volume or displacement.

Adult↗

Bronchoconstriction: upper airway dilating muscle and diaphragm activity.

The effect of bronchoconstriction on the activity of the diaphragm and the upper dilating airway muscles were studied by administering graded doses of methacholine to anesthetized dogs spontaneously breathing oxygen. The electrical activity of the genioglossus, posterior cricoarytenoid, and alae nasi was compared with that of the diaphragm at different levels of pulmonary resistance. Induced bronchoconstriction was associated with increases in the electrical activity of all muscles examined. Bilateral cervical vagotomy diminished but did not prevent the bronchoconstrictor effects of methacholine. When greater concentrations of methacholine were administered to produce bronchoconstriction comparable with that produced prevagotomy, both genioglossus and diaphragm activity increased. This study indicates that the upper airway muscles and the diaphragm respond to bronchoconstriction. The activation of the upper airway muscles with bronchoconstriction may decrease upper airway resistance serving to partially offset increases in pulmonary resistance and to modulate airflow patterns during bronchoconstriction.

Airway Resistance↗

Effect of histamine on respiratory chemosensitivity in conscious goats.

The effect of histamine on occlusion pressure and electrical activity of the diaphragm was studied in 5 conscious goats under conditions of changing respiratory drive by exposing the animals in separate trials to progressive hypercapnia produced by rebreathing technique. Both electrical activity of the diaphragm and occlusion pressure increased with hypercapnia. At any level of PCO2, occlusion pressure and diaphragm electrical activity were greater after histamine than in the control state at the same level of chemical stimulation. Both parameters changed proportionally, and a linear correlation was found between them (r greater than 0.9). These results in conscious unsedated animals indicate that (1) histamine causes an increase of inspiratory neuromuscular drive, and (2) occlusion pressure satisfactorily indicates changes in respiratory neuron motor output.

Animals↗

Effect of respiratory loading on the relationship between occlusion pressure and diaphragm EMG during hypoxia and hypercapnia.

In 7 conscious, unsedated goats with chronically implanted diaphragm electrodes, the effect of respiratory loading on the relationship between occlusion pressure and diaphragm EMG was studied. Diaphragm electrical activity (ED) quantified by the moving average technique was measured in separate trials during progressive hyperoxic hypercapnia and progressive isocapnic hypoxia, both before and after inspiratory resistance had been increased by externally applied loads. Airway occlusion was performed during inspiration on random breaths at functional residual capacity, and the maximum negative pressure (Pmax) was measured. In all 7 goats, occlusion pressure was greater with external loads (EL) than control. The peak ED of unoccluded breaths was greater with EL than control in all animals during hypoxia but in only 3 of the animals during hypercapnia. In half of the trials, the ratio of Pmax to ED of occluded or unoccluded breaths was higher with EL than control. In the remaining studies, the ratio was the same. FRC was unaffected by EL. In the one goat in which it was measured, intercostal EMG was also greater during EL than control. These results suggest that the inspiratory muscles other than the diaphragm are recruited during EL causing the Pmax to ED ratio to rise even if neuromechanical coupling remains unchanged. It is speculated that in conscious, unsedated animals, acute increases in the resistance to air flow affect the distribution of respiratory motor activity.

Animals↗

Diaphragm activation with intramuscular stimulation in dogs.

We studied in 10 supine anesthetized dogs diaphragm contraction produced by electrical activation with intramuscular electrodes surgically implanted in the ventral surface of the diaphragm and compared this with activation of the ipsilateral phrenic nerve (C5, 6, and 7) before it entered the thorax. Repetitive 40-Hz pulse trains with supramaximal current stimulus were used after hyperventilation of the animals to apnea. A single intramuscular electrode within 1 to 2 cm of the site of phrenic nerve entry into the diaphragm produced a mean transdiaphragmatic pressure of 12.0 cm H2O +/- 0.97 SE and mean tidal volume of 0.27 L +/- 0.04 SE. Mean values observed with phrenic nerve stimulation were not statistically different, and both electrode systems produced equivalent outward abdominal motion and upper rib cage paradox, as monitored by inductive plethysmography. There was no difference in gas exchange during stimulation with a single hemidiaphragm electrode and mechanical ventilation compared at the same tidal volume and respiratory rate. Blockade of neuromuscular transmission with curare eliminated intramuscular and phrenic nerve stimulation proportionately, suggesting that activation of the diaphragm is dependent in both cases on the phrenic nerve. This technique does not entail manipulation of the phrenic nerve and may have clinical application as an alternative technique for diaphragm pacing.

Animals↗

Occlusion pressure and breathing pattern in patients with interstitial lung disease.

The ventilatory and occlusion pressure (P100) responses to hypercapnia, maximal inspiratory airway and transdiaphragmatic pressures, and the separate volume contributions of the rib cage and abdomen to tidal breathing were evaluated in 16 patients with chronic stable interstitial lung disease. Compared with those in the normal subjects, ventilation and P100 at a PCO2 = 55 mmHg were significantly higher (p less than 0.05 and p less than 0.01, respectively) in the patients with interstitial lung disease. However, the ventilatory and occlusion pressure responses to hypercapnia (delta VE/delta PCO2 and delta P 100/delta PCO2, respectively) were not significantly different between the groups. Maximal inspiratory airway pressure was significantly reduced in the patient group (p less than 0.05); maximal transdiaphragmatic pressure was also reduced but not significantly. At any given level of ventilation, tidal volume was decreased and breathing frequency increased in the patients with interstitial lung disease (p less than 0.05). The greater respiratory frequency was caused by reductions in both expiratory and inspiratory time. Because of smaller tidal volumes, rib cage expansion was reduced in the group of patients when compared with that in normal subjects during both spontaneous breathing and when compared at the same level of hypercapnia; abdomen volume was reduced to a lesser extent. We conclude that in patients with interstitial lung disease, non-chemical, presumably neural, mechanisms, increase respiratory drive and alter the breathing pattern. We speculate that both vagal mechanisms and mechanoreceptors in the chest wall sensitive to rib cage expansion contribute to these responses.

Adult↗

Mechanisms underlying CO2 retention during flow-resistive loading in patients with chronic obstructive pulmonary disease.

The present study examined the respiratory responses involved in the maintenance of eucapnea during acute airway obstruction in 12 patients with chronic obstructive disease (COPD) and 3 age-matched normal subjects. Acute airway obstruction was produced by application of external flow-resistive loads (2.5 to 30 cm H2O/liter per s) throughout inspiration and expiration while subjects breathed 100% O2. Application of loads of increasing severity caused progressive increases in PCO2 in the patients, but the magnitude of the increase in PCO2 varied substantially between subjects. On a resistance of 10 cm H2O/liter per s, the highest load that could be tolerated by all COPD patients, the increase in PCO2 ranged from 1 to 11 mm Hg, while none of the normal subjects retained CO2. Based on the magnitude of the increase in PCO2 the patients could be divided into two groups: seven subjects whose PCO2 increased by less than or equal to 3 mm Hg (group I) and five subjects whose PCO2 increased by greater than 6 mm Hg (group II). Base-line ventilation and the pattern of breathing were similar in the two groups. During loading group I subjects maintained or increased tidal volume while all group II patients decreased tidal volume (VT). The smaller tidal volume in group II subjects was mainly the result of their shorter inspiratory time as the changes in mean inspiratory flow were similar in the two groups. The magnitude of CO2 retention during loading was inversely related to the magnitude of the change in VT (r = -0.91) and inspiratory time (Ti) (r = -0.87) but only weakly related to the change in ventilation (r = -0.53). The changes in PCO2, VT, and Ti during loading correlated with the subjects' maximum static inspiratory pressure, which was significantly lower in group II as compared with group I patients. These results indicate that the tidal volume and respiratory timing responses to flow loads are impaired in some patients with COPD. This impairment, presumably due to poor inspiratory muscle function, appears to lead to CO2 retention during loaded breathing.

Aged↗

Sleep apnea considered as a control system instability.

In the present study a mathematical model of the chemical control of respiration is described which attempts to simulate periodic breathing during sleep. The model is an extension of an earlier model which has been shown to successfully reproduce the transient effects of CO2 inhalation on breathing, controlled changes in ventilation on arterial gas tension, and Cheyne-Stokes breathing. Included in the extended model are the effects of chemical stimuli during sleep on both chest wall and upper airway muscle activity. Data is presented indicating that simulations from the model reproduce reasonably well the essential features of the results obtained in eight subjects with periodic respiration during sleep when breathing room air, O2, or low concentrations of CO2. Simulations from the model and the experimental data suggest that periodic breathing during sleep results from unstable operation in the respiratory control system analogous to that seen during instabilities in physical control systems. The model indicates that obstructive as well as central apneas can be produced by control system instability. Furthermore, central apneas increase the likelihood of obstructive apneas while obstructive apneas tend to aggravate the control instability. The model results predict that the characteristics of the periodic breathing seen during sleep, such as apnea length, will depend on circulation time and the sensitivity of both upper airway and chest wall muscles to hypercapnia and hypoxia.

Air↗

Effect of aging on respiratory responses to CO2 and inspiratory resistive loads.

We studied 10 elderly individuals over 60 years of age and 18 individuals less than 30 years to determine whether aging affects the response of the respiratory control system to chemical stimuli or to altered mechanical conditions. Both groups consisted of males and females who were nonsmokers. Ventilation and the isometric force developed by the inspiratory muscles (occlusion pressure) was assessed during hypercapnia while the subjects breathed under control conditions or through a load at the mouth that increased inspiratory resistance. Ventilation responses to progressively increasing CO2 were lower but not significantly so in the older group. There were significant differences in ventilatory pattern in the two groups. However, occlusion pressure responses to hypercapnia and to resistive loads were the same. The results suggest that aging has little or no adverse effect on respiratory control.

Adult↗

Effect of chemical stimuli on nerves supplying upper airway muscles.

Studies of upper airway resistance suggest that the activity of cranial nerves supplying upper airway muscles changes with chemical drive and that imbalances in the activation of these nerves as compared to the phrenic play a role in causing upper airway obstruction. We assessed the effect of hypoxia and hypercapnia on the activity of the hypoglossal nerve, the recurrent laryngeal nerve, and phrenic nerve in paralyzed anesthetized artificially ventilated dogs. Comparison of hypoglossal and phrenic nerves were also repeated after vagotomy. Both hypoglossal and recurrent laryngeal nerves exhibited increased activity with inspiration. Hypoxia and hypercapnia increased phrenic nerve activity as well as the activity of the two cranial nerves. While linear increases occurred in phrenic and recurrent laryngeal nerve activity with both chemical stimuli, the relationship between hypoglossal and phrenic nerve activity was curvilinear. At lower levels of chemical drive, changes in hypoglossal nerve were less than in the phrenic, and the reverse was true at higher levels of chemical stimulation. There were also differences in the response of both cranial nerves and the phrenic to changing vagal stimulation. The dissimilarities observed in the cranial response of the nerves (versus the phrenic) could potentially affect the forces developed during inspiration and lead to obstruction in the upper airway.

Airway Resistance↗

Central and peripheral chemoreceptor inputs to phrenic and hypoglossal motoneurons.

We tested the hypothesis that phrenic and hypoglossal responses to progressive hypercapnia differ qualitatively because the CO2-related drive inputs to their respective motoneuron pools are different. The relative contributions of carotid sinus and central chemoreceptor inputs to hypoglossal and phrenic responses during hyperoxic hypercapnia were determined by comparing the two nerve activities during rebreathing runs done either before and after bilateral carotid sinus nerve (CSN) section, or without and with cooling of the intermediate, I(s), area on the ventral surface of the medulla. The studies were performed on chloralose-anesthetized, vagotomized, paralyzed cats. Cooling of the I(s) area impaired phrenic responsiveness to hypercapnia more than hypoglossal responsiveness, whereas CSN section had the opposite effect. Thus phrenic nerve response was more dependent on central chemoreceptor input than was the hypoglossal response, but hypoglossal response was more dependent on carotid sinus chemoreceptor input. We conclude that the phrenic and hypoglossal motoneuron pools each receive a different functional input from both the medullary and the carotid sinus chemoreceptors.

Action Potentials↗

Effect of progressive hypoxia on breathing during sleep.

We examined the effects of progressive hypoxia on breathing during wakefulness and quiet (NREM) sleep in 17 healthy young adults (11 males and 6 females). Ventilation was determined from quantitative measurements of abdominal and rib cage excursions using magnetometers or inductive plethysmography. Hypoxia was induced by blending N2 into the inspiratory line of a loose-fitting mask while O2 saturation was monitored with an ear oximeter. No attempt was made to maintain isocapnia. Ventilatory responses to hypoxia were depressed in 2 male subjects by sleep, but were unchanged or increased in the others. Thus on the average, sleep produced no change in ventilatory responses to hypoxia. There was no consistent difference in the frequencies or tidal volumes attained at a given level of ventilation during hypoxia awake and asleep. During sleep there was relatively more rib cage than abdominal movement. Relief of hypoxia was followed by periodic breathing during sleep in 12 subjects but in only 2 subjects when awake. In two thirds of the trials, hypoxia failed to produce arousal even though arterial O2 saturation was allowed to fall below 75%. The results suggest that (1) sleep potentiates apnea producing effects of O2 changes but has inconsistent effects on ventilatory responses to hypoxia, and (2) hypocapnic hypoxia is not an invariably potent stimulus for arousal.

Abdomen↗

Effect of aging on the perception of resistive ventilatory loads.

We have shown previously, using the technique of magnitude estimation, that the change in sensation level for a given change in elastic loading is less in elderly than in young subjects. In the present study, we used the same technique to compare the perception of added inspiratory and expiratory resistive loads in 40 young (18 to 30 yr of age) and 19 elderly (60 yr of age and older) subjects. Two different ranges of loads were studied and the relation between load magnitude and sensation intensity (the exponent for magnitude estimation) was determined. The study showed that the exponent for both inspiratory and expiratory loads is less in the older group. Because peak airway pressure and the inspiratory and expiratory times while breathing against the added loads were the same in both age groups, the difference in exponents in the two groups was not caused by differences in the forces generated during breathing. Age-related changes in sensory perception may affect behavioral responses to impaired respiratory mechanics.

Adolescent↗