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J C Leiter

Publications and source records attributed to J C Leiter.

16 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

Ventilatory and hematopoietic responses to chronic hypoxia in two rat strains.

Hilltop (H) and Madison (M) strains of Sprague-Dawley rats exhibit strikingly different susceptibilities to the effects of chronic altitude exposure. The H rats develop greater polycythemia, hypoxemia, and pulmonary hypertension. We studied ventilation, pulmonary gas exchange, tissue oxygenation, and hematologic adaptations in the two rat strains during a 50-day exposure to a simulated altitude (HA) of 5,500 m (18,000 ft). There were no strain differences among the variables we studied under sea level (SL) conditions. Within the first 14 days of hypoxic exposure, the only significant strain differences were that erythropoietin (EPO) rose much higher and erythroid activity was greater in the H rats, even though arterial Po2 and PCo2 (Pao2 and PaCo2, respectively), renal venous PO2 (Prvo2), and ventilation (VE) were equivalent in the two strains during this time. By day 14 at HA, the H rats had significantly higher erythroid activity, hematocrit (Hct), and EPO levels, significantly lower PaO2 and PrvO2, but equivalent VE and PaCO2. These changes persisted for the remainder of the exposure, except that the Hct continued to rise and the increase was greater in H rats. Despite the greater O2-carrying capacity of H rats in the later stages of hypoxic exposure, PaO2 and PrvO2 were significantly lower in H rats. There were no strain differences at either SL or HA in ventilatory responses to hypercapnia or hypoxia, in blood O2 affinity or 2,3-diphosphoglycerate, in extrarenal production of EPO, or in EPO clearance. We conclude that early in the hypoxic exposure the H rats produce more EPO at apparently equivalent levels of hypoxia, and this is the first step in the pathogenesis of the maladaptation to HA manifest by H rats. We find no consistent evidence that differences in VE contribute to the variable susceptibility to hypoxia in the two rat strains.

Altitude Sickness↗
PubMed1992

Analysis of pharyngeal resistance and genioglossal EMG activity using a model of orifice flow.

A model of orifice flow has been used to analyze the relationships among pressure, flow, and genioglossal electromyographic activity in the human pharynx during inspiration. The orifice flow model permits one to assess the character of airflow (laminar or turbulent) and to estimate the cross-sectional area of the orifice from pressure and flow measurements. On the basis of other data (J. Appl. Physiol. 73: 584-590, 1992), this analysis suggests that pharyngeal airflow is turbulent. Furthermore the area of the pharynx appears to increase as flow increases, but the actual change in pharyngeal diameter necessary to fit the pressure-flow data is quite small (0.11-0.87 cm, depending on the assumptions in the model). The flow-related increase in orifice area can be attributed, in part, to the activation of the genioglossus muscle. However, other flow-related factors may also contribute to pharyngeal dilation as airflow increases. Different airway shapes (circular and elliptical) and orientations (major axis anteroposterior and lateral) were incorporated into the model calculations; these factors modify considerably the apparent efficiency of genioglossal electromyographic activity. Genioglossal muscle shortening increases pharyngeal area and reduces pharyngeal resistance more effectively when the pharynx is elliptical, with the long axis of the ellipse oriented laterally. Hence the genioglossus may operate at a significant mechanical disadvantage in those patients with obstructive sleep apnea with a small sagittally oriented pharyngeal lumen.

Airway Resistance↗
PubMed1992

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↗
PubMed1991

Nasal and pharyngeal resistance after topical mucosal vasoconstriction in normal humans.

Phenylephrine, an alpha-adrenergic agonist, increases pharyngeal cross-sectional area when applied topically to the nasal and pharyngeal mucosa, as determined by magnetic resonance imaging. In this study, we examined the possibility that the increase in area results from either a decrease in transmural collapsing pressure, as a result of a decrease in upstream (nasal) resistance, or an increase in upper airway muscle activity. In eight normal, awake men we measured inspiratory pharyngeal and nasal resistance and the electrical activity of the genioglossus (EMGGG) and alae nasi (EMG(AN) before and after pharyngeal and nasal + pharyngeal instillation of 1 ml of either 0.25% phenylephrine or normal saline; phenylephrine and saline were tested on separate days. Under control eucapnic conditions, pharyngeal resistance was 0.43 +/- 0.03 cm H2O/L/s, and nasal resistance was 2.43 +/- 0.14 cm H2O/L/s. Pharyngeal resistance was 0.29 +/- 0.03 cm H2O/L/s after nasal + pharyngeal instillation of phenylephrine and 0.98 +/- 0.13 cm H2O/L/s after saline; nasal resistance was 2.18 +/- 0.13 cm H2O/L/s after nasal + pharyngeal instillation of phenylephrine and 3.15 +/- 0.21 cm H2O/L/s after saline. Thus, phenylephrine decreased both nasal and pharyngeal inspiratory resistance. The change in pharyngeal resistance was not dependent on the change in nasal resistance. Eucapnic EMGGG and EMGAN activities did not change after phenylephrine or saline. We conclude that phenylephrine decreased pharyngeal resistance independent of a change in nasal resistance of upper airway muscle activity, and we believe that the changes in resistance we observed reflect a direct effect of phenylephrine on the pharyngeal mucosa and a consequent enlargement of pharyngeal size.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗
PubMed1990

Acute histologic effects of simulated large-volume aspiration of sucralfate into the lungs of rats.

Sucralfate is an effective agent in reducing the incidence of upper GI tract (UGIT) stress bleeding and nosocomial pneumonia in critically ill patients. Many of these patients are not intubated and are at increased risk for aspiration of large volumes of UGIT contents containing sucralfate. The effects of aspirated sucralfate are unknown. To investigate this, large-volume aspiration (2 ml/kg) was simulated in freshly tracheostomized rats (n = 6, all experimental groups) using normal saline, particulate antacid, and sucralfate adjusted to pH 3.6 and 5.0. Four hours after aspiration, the rats were killed and their lungs were formalin-fixed. Significant increases in lung inflammation were seen by light microscopy in all experimental groups at pH 3.6. Antacid aspirated at pH 5.0 induced significant increases in airway as well as parenchymal inflammation. At pH 3.6, the antacid aspiration led to significant increases in lung edema and hemorrhage. Sucralfate aspiration produced significant increases in pulmonary hemorrhage at pH 5.0. Our microscopic findings are consistent with the acute pulmonary histopathologic changes known to occur after large-volume aspiration of particulate materials, including antacids. Additionally, we show that large-volume aspiration of sucralfate produced significant acute pneumonitis, including pulmonary hemorrhage. In view of the proven usefulness of sucralfate, further investigations are indicated to evaluate these experimental findings before extrapolating to critically ill patients.

Aluminum Hydroxide↗
PubMed1990

Selective reflex activation of the genioglossus in humans.

In anesthetized or decerebrate animals, negative pressure applied to the upper airway selectively activates the hypoglossal nerve compared with the phrenic nerve. Conversely, positive pressure reduces hypoglossal nerve activity out of proportion to any change in the phrenic neurogram. We have tested the hypothesis that analogous pressure changes applied to awake humans would selectively inhibit or activate genioglossal electromyographic (EMGge) activity relative to diaphragmatic electromyographic activity (EMGdi). We studied seven normal subjects in a head-out body plethysmograph. Pressure at the mouth was either atmospheric, +10 cmH2O, or -10 cmH2O, and lung volume was held constant by applying an identical pressure to the body surface. Thus the transmural pressure distorting the respiratory system was applied only to the upper airway. Subjects breathed CO2-enriched (2-3%) room air to stimulate phasic respiratory EMGge activity. We found that -10 cmH2O pressure applied selectively to the upper airway resulted in a 49% enhancement of peak-integrated EMGge activity, but EMGdi activity remained at control levels. Positive pressure did not result in any changes in EMGge or EMGdi activity. Neither pressure resulted in significant changes in the magnitude or pattern of ventilation. We conclude that reflex mechanisms maintaining upper airway patency are demonstrable in awake humans and probably have an important role in moment-to-moment modulation of upper airway muscle activity in normal awake humans.

Adolescent↗
PubMed1989

Partitioning of ventilation between nose and mouth: the role of nasal resistance.

We have examined the relationship between nasal resistance (Rna) and the distribution of ventilation between the nose and mouth in 10 normal breathing children and 15 children who met clinical criteria of mouth breathing. We studied Rna by posterior rhinometry. We used a face mask divided into separate oral and nasal chambers to measure oral and nasal components of ventilation. Each chamber of the mask was connected to a separate pneumotachograph. We measured oral and nasal tidal volumes (VTna) by integration of the oral and nasal flow, and calculated the total tidal volume (VTtot) by summing the oral and nasal components. The nasal fraction of ventilation (F-VTna) was calculated by dividing VTna by VTtot. We found a weak inverse correlation between Rna and F-VTna, but eight of 25 children did not breathe as one might predict on the basis of Rna, and eight of 15 children who appeared to be mouth breathers actually breathed through the nose. We administered a vasoconstricting nasal spray and a placebo nasal spray to the children and, although Rna changed significantly, we observed no change in the distribution of flow between the nose and mouth. In summary we found that clinical criteria of mouth breathing do not accurately identify children who actually breathe mainly through the mouth. Moreover Rna is only a weak predictor of the pattern of breathing; hence other factors may be important determinants of the distribution of flow between the nose and mouth.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1989

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↗
PubMed1987

Respiratory activity of genioglossus. Interaction between alcohol and the menstrual cycle.

Alcohol consistently decreases genioglossal electromyographic (EMG) activity in awake men, but in women this response is more variable, possibly because of the menstrual cycle. To assess the interaction between alcohol and the menstrual cycle on genioglossal EMG activity, we measured ventilation and genioglossal EMG activity in 9 normal women before and after they drank 1 ml/kg alcohol. The effect of alcohol on ventilation and genioglossal EMG activity was studied twice in each subject: once during the follicular phase and again during the luteal phase of the menstrual cycle. Measurements were made while the subjects breathed room air and rebreathed a hypercapnic gas mixture. The ventilatory response to CO2 was significantly greater during the luteal phase of the menstrual cycle. Alcohol had no effect on resting ventilation or the ventilatory response to CO2 during either phase of the menstrual cycle. However, alcohol significantly decreased peak integrated genioglossal EMG activity during the follicular (low progesterone) phase but not during the luteal (high progesterone) phase of the cycle. The relative alcohol resistance of genioglossal EMG activity during the luteal phase may explain in part the low incidence of sleep-disordered breathing in premenopausal women and the benefit that some male patients with obstructive sleep apnea have derived from treatment with progesterone.

Adult↗
PubMed1986

Hyperoxic ventilatory responses of high altitude acclimatized cats.

We have examined the effect of steady-state hyperoxia on the ventilation of sea level (SL) cats and cats acclimatized to simulated high altitude (HA) at 5500 m for three weeks. Three groups of cats were studied. In group I, the ventilatory responses to 10%, 21% and 100% O2 were studied at SL, and after acclimatization to HA, the ventilatory responses to 10% and 100% O2 were measured. In group II the ventilatory responses and femoral artery and superior sagittal sinus blood gases were measured in two sets of cats, one at SL and one at HA, during exposure to the gases outlined in group I. In group III, we examined the effect of chronic vagotomy on the ventilatory responses to the gas mixtures outlined in group I. Breathing 100% O2 at SL had no significant effect on ventilation, tidal volume, respiratory frequency, or cerebral blood flow (inferred from the cerebral veno-arterial CO2 difference). Ventilation was constant in the HA acclimatized cats while breathing 10% and 100% O2, but the ventilatory pattern changed dramatically during hyperoxia: respiratory frequency increased and tidal volume fell. Breathing 100% O2 was associated with changes in CBF, and venous PCO2 that might be expected to stimulate ventilation, but the change in ventilatory pattern suggests to us that hyperoxic disinhibition of central respiratory processes (which were modified by HA acclimatization) is the mechanism whereby ventilation is sustained during hyperoxia at HA. After vagotomy at HA, ventilation remained constant while breathing 100% O2, but the changes in respiratory pattern were no longer apparent. Therefore, vagal afferents seems to have a role in determining the pattern, but not necessarily the absolute level, of ventilation during hyperoxia. Cats vagotomized at SL prior to HA exposure did not show any evidence of HA ventilatory acclimatization; thus, the vagi may also play a heretofore unrecognized role in the process of acclimatization.

Acclimatization↗
PubMed1986

A comparative analysis of contractile characteristics of the diaphragm and of respiratory system mechanics.

The mean inspiratory flow rate (VT/TI) is used as an index of central respiratory 'drive', and, at rest, it varies interspecifically in proportion to body weight (BW) raised to the 0.74 power (Boggs and Tenney, 1984). VT/TI is determined by the level of central neural respiratory output, the velocity of contraction of respiratory muscles, and the mechanical characteristics of the respiratory system. We have examined the last two factors in 13 species ranging in weight from 0.025 to 515 kg. We determined the 'effective' inspiratory mechanical characteristics of the respiratory system (time constant, resistance, and compliance) and the time course of diaphragmatic contraction during bilateral supramaximal phrenic nerve stimulation in anesthetized animals. We also measured passive expiratory mechanical variables and made morphometric measurements of the diaphragm. We found that VT/TI during phrenic nerve stimulation was proportional to BW0.82. The 'effective' respiratory time constant (tau'rs) and passive expiratory time constant (tau rs) scaled in proportion to body weight with nearly similar exponents: tau'rs alpha BW0.26 and tau rs alpha BW0.21. In addition, the time constant of diaphragmatic contraction (tau mc) was proportional to BW0.20. Inspiratory time is proportional to tau'rs and tau mc, and tidal volume during stimulation was almost directly proportional to body weight. Thus, interspecific changes in VT/TI during stimulation were related to interspecific changes in the mechanical characteristics of the respiratory system and the velocity of muscular contraction. We conclude that interspecific changes in VT/TI need not reflect interspecific variation in central respiratory drive under resting conditions. We found that diaphragm weight and volume and diaphragm muscle thickness were geometrically similar in all species studied. Inspiratory pressure is an interspecific constant; therefore, by the Law of Laplace, smaller animals must develop greater tension per unit of muscle mass.

Airway Resistance↗
PubMed1985

A noninvasive intraoral electromyographic electrode for genioglossus muscle.

We have developed an intraoral bipolar surface electrode for the genioglossus muscle. The electrode, made from an athletic mouthguard and dental impression material, was fitted to the lower teeth. Electrode wires, bared at the tip, were positioned on the bottom of the mouthpiece to lie in contact with the superior surface of the genioglossus just behind the teeth. The electromyographic activity of the genioglossus, simultaneously obtained from the surface electrode and conventional intramuscular electrodes, was compared during quiet breathing, CO2 rebreathing, and a variety of tongue movements. The two types of electrodes recorded similar patterns of muscle activity, and spectral analyses of the signals revealed similar and highly coherent frequency spectra. We conclude that the surface electrode satisfactorily reflects the bioelectrical activity of the genioglossus. The mouthpiece electrode has the further advantage that quantitative comparisons can be made among recordings made in different experimental sessions, since the fit of the mouthpiece to the teeth assures a constant relationship of the electrode to the genioglossus muscle.

Adult↗
PubMed1985

The effect of diazepam on genioglossal muscle activity in normal human subjects.

We examined the effect of diazepam on the respiratory electromyographic (EMG) activity of the genioglossal muscle using a double-blind, placebo-controlled, randomized protocol. Control measurements of minute ventilation, tidal volume, frequency, end-tidal CO2, and peak integrated inspiratory genioglossal EMG activity were made in 10 normal awake male subjects during quiet breathing and CO2 rebreathing. Subjects then received either 10 mg of diazepam orally or a placebo, and all respiratory measurements were repeated after 45 min. Each subject was studied on 2 separate days, receiving each treatment on a different day. The placebo had no effect on any of the measured variables. After diazepam, we observed an increase in end-tidal CO2 rebreathing, diazepam was associated with a reduction in minute ventilation, tidal volume, and frequency. When compared at equal end-tidal CO2 levels, genioglossal EMG activity and tidal volume were significantly reduced after diazepam. However, only older subjects demonstrated a reduction in EMG activity when compared at equal tidal volumes during CO2 rebreathing. We conclude that diazepam selectively decreases genioglossal EMG activity during CO2 rebreathing only in older subjects.

Adult↗
PubMed1985

The effect of sleep deprivation on activity of the genioglossus muscle.

Sleep deprivation appears to increase the severity of obstructive sleep apnea, and inadequate activation of the genioglossus muscle may play an important role in the pathogenesis of obstructive sleep apnea. Therefore, we investigated the effect of sleep deprivation on genioglossal electromyographic (EMG) activity. Eleven men were studied during room air breathing and CO2 rebreathing before sleep deprivation (control), after 1 night of sleep deprivation, and the day after sleep recovery. We measured inspired minute ventilation, tidal volume, respiratory frequency, and peak integrated inspiratory genioglossal EMG activity. After sleep deprivation, no significant changes in inspiratory minute ventilation or tidal volume occurred during room air breathing or CO2 rebreathing, but the breathing frequency during CO2 rebreathing increased significantly after sleep deprivation. Genioglossal EMG activity was diminished during CO2 rebreathing after sleep deprivation, but this was significant only in subjects 30 yr of age and older. The fall in EMG activity was independent of changes in tidal volume. All variables returned towards control levels after sleep recovery. We conclude that sleep deprivation selectively decreases genioglossal EMG activity during CO2 rebreathing in awake older subjects. This influence of sleep deprivation may play a role in the pathogenesis or severity of obstructive sleep apnea.

Adult↗