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Biomedical subjects

Ralph F Fregosi

Publications and source records attributed to Ralph F Fregosi.

18 recordsLinked to original sources
PubMed2006

Anatomic consequences of intrinsic tongue muscle activation.

We recently showed respiratory-related coactivation of both extrinsic and intrinsic tongue muscles in the rat. Here, we test the hypothesis that intrinsic tongue muscles contribute importantly to changes in velopharyngeal airway volume. Spontaneously breathing anesthetized rats were placed in a MRI scanner. A catheter was placed in the hypopharynx and connected to a pressure source. Axial and sagittal images of the velopharyngeal airway were obtained, and the volume of each image was computed at airway pressures ranging from +5.0 to -5.0 cm H2O. We obtained images in the hypoglossal intact animal (i.e., coactivation of intrinsic and extrinsic tongue muscles) and after selective denervation of the intrinsic tongue muscles, with and without electrical stimulation. Denervation of the intrinsic tongue muscles reduced velopharyngeal airway volume at atmospheric and positive airway pressures. Electrical stimulation of the intact hypoglossal nerve increased velopharyngeal airway volume; however, when stimulation was repeated after selective denervation of the intrinsic tongue muscles, the increase in velopharyngeal airway volume was significantly attenuated. These findings support our working hypothesis that intrinsic tongue muscles play a critical role in modulating upper airway patency.

Airway Obstruction↗
PubMed2006

Modulation of upper airway muscle activities by bronchopulmonary afferents.

Here we review the influence of bronchopulmonary receptors (slowly and rapidly adapting pulmonary stretch receptors, and pulmonary/bronchial C-fiber receptors) on respiratory-related motor output to upper airway muscles acting on the larynx, tongue, and hyoid arch. Review of the literature shows that all muscles in all three regions are profoundly inhibited by lung inflation, which excites slowly adapting pulmonary stretch receptors. This widespread coactivation includes the recruitment of muscles that have opposing mechanical actions, suggesting that the stiffness of upper airway muscles is highly regulated. A profound lack of information on the modulation of upper airway muscles by rapidly adapting receptors and bronchopulmonary C-fiber receptors prohibits formulation of a conclusive opinion as to their actions and underscores an urgent need for new studies in this area. The preponderance of the data support the view that discharge arising in slowly adapting pulmonary stretch receptors plays an important role in the initiation of the widespread and highly coordinated recruitment of laryngeal, tongue, and hyoid muscles during airway obstruction.

Airway Obstruction↗
PubMed2005

Respiratory-related discharge of genioglossus muscle motor units.

RATIONALE: Little is known about the respiratory-related discharge properties of motor units driving any of the eight muscles that control the movement, shape, and stiffness of the mammalian tongue. OBJECTIVES: To characterize the respiratory-related discharge of genioglossus motor units as synaptic drive to the hypoglossal motoneuron pool is increased with hypercapnia. MEASUREMENTS: We recorded airflow, genioglossus muscle EMG activity, and the respiratory-related discharge of 30 genioglossus muscle motor units in spontaneously breathing, urethane-anesthetized rats under control conditions and in hypercapnia (inspired CO2: 3, 6, 9, and 12%, 3-5 min at each level). MAIN RESULTS: All motor units were active throughout all or most of inspiration. Nine of 30 units showed "preinspiratory" activity (discharge onset within the last 20% of expiration), with continued discharge into inspiration. Six inspiratory units transitioned to a preinspiratory pattern when inspired CO2 exceeded 6%. For the majority of units (23/30), discharge rate increased with hypercapnia, with the maximum increase averaging about 50%. The average variability of interspike intervals within a spike train increased from 33% under baseline conditions to 50% with maximal hypercapnia. CONCLUSIONS: (1) The discharge pattern of genioglossus muscle motor units can be altered by hypercapnia; (2) most, but not all, genioglossus motor units receive synaptic input from CO2-sensitive chemoreceptors; (3) individual motor units have a wide range of CO2 sensitivities; and (4) hypercapnia significantly increases the variability of motor unit discharge, which may enhance muscle force output.

Action Potentials↗
PubMed2005

PO2-dependent changes in intrinsic and extrinsic tongue muscle activities in the rat.

RATIONALE: Historically, respiratory-related research in sleep apnea has focused exclusively on the extrinsic tongue muscles (i.e., genioglossus, hyoglossus, and styloglossus). Until recently, the respiratory control and function of intrinsic tongue muscles (i.e., inferior and superior longitudinalis, transverses, and verticalis), which comprise the bulk of the tongue, were unknown. OBJECTIVES: The current study sought to determine if extrinsic and intrinsic tongue muscles are coactivated in conditions of hypoxemia comparable to that experienced by adults with obstructive sleep apnea. MEASUREMENTS: Esophageal pressure and EMG activity of an extrinsic (hyoglossus) and an intrinsic (superior longitudinal) tongue muscle were studied in anesthetized, tracheotomized, spontaneously breathing rats. Average EMG activity was compared in a control gas condition (Pa(O2), 160 +/- 12 mm Hg) and in mild isocapnic hypoxia (Pa(O2), 69 +/- 7.2 mm Hg), with and without brief (3-breath) airway occlusions, pre- and postbilateral vagotomy. MAIN RESULTS: (1) intrinsic and extrinsic tongue muscles are coactivated in mild hypoxia, (2) airway occlusion increased the activities of intrinsic retractor muscles in mild hypoxia, and (3) extrinsic retractor muscles have a steeper rate of rise of activity and an earlier burst onset relative to intrinsic retractor activities in mild hypoxia. CONCLUSIONS: These findings support our working hypothesis that airway patency is maintained not simply by activation of extrinsic tongue muscles but by the coactivation of intrinsic and extrinsic protrudor and retractor muscles.

Airway Obstruction↗
PubMed2004

Prenatal nicotine exposure increases the strength of GABA(A) receptor-mediated inhibition of respiratory rhythm in neonatal rats.

Infants born to mothers that smoke while pregnant have a relatively high incidence of central respiratory control abnormalities. Recent studies have shown that prenatal nicotine exposure increases GABA release and the frequency of GABAergic currents, leading to an up-regulation of GABA(A) receptors in central neurones. Activation of GABA(A) receptors inhibits ventilatory activity, with intense activation causing apnoea. These observations lead us to hypothesize that prenatal nicotine exposure alters GABAergic control of respiratory motor pattern in the early neonatal period. Osmotic minipumps were implanted in pregnant Sprague-Dawley rats on the fifth day of gestation, and filled with nicotine (6 mg kg(-1) day(-1), 2.5 microl h(-1)) or physiological saline (2.5 microl h(-1)). Brainstem-spinal cord preparations from 1- to 3-day-old neonates were studied under in vitro conditions. Electrical activity was recorded from the fourth cervical ventral root (C4 VR), which contains the axons of phrenic motoneurones. Bath application of GABA(A) receptor agonists muscimol (250 microM) or pentobarbital sodium (60 microM) to the brainstem led to consistent, reversible and significant reductions in C4 VR burst frequency. In saline-exposed animals, frequency (bursts min(-1)) fell from 6.8 +/- 0.4 to a nadir of 2.8 +/- 0.5 with muscimol, and from 6.5 +/- 0.3 to a nadir of 2.9 +/- 0.3 for pentobarbital; in nicotine-exposed animals, frequency fell from 6.3 +/- 0.4 to 1.0 +/- 0.4 with muscimol and from 6.4 +/- 0.2 to 1.7 +/- 0.4 with pentobarbital (P < 0.05 in all cases). The decrease in C4 VR frequency was significantly greater in nicotine-exposed compared to saline-exposed preparations with both muscimol and pentobarbital (P < 0.001 for both). There were no changes in the amplitude of C4 VR bursts under any condition. The GABA(A) receptor antagonist bicuculline methiodide (8 microM) did not change C4 VR frequency or amplitude in either group, although it was effective in reversing the effects of muscimol. These experiments demonstrate that prenatal nicotine exposure alters the GABAergic regulation of respiratory rhythm in a reduced preparation. The results may lead to a better understanding of the perturbed breathing pattern observed in neonates that are exposed to nicotine in utero.

Animals↗
PubMed2004

Influence of prenatal nicotine exposure on postnatal development of breathing pattern.

To determine if prenatal nicotine exposure alters the postnatal development of the ventilatory pattern and the frequency and duration of apneas, we recorded respiratory airflow with head-out body plethysmography in awake neonates on postnatal days 1, 2, 6, 10, 14, and 18. Data from 12 nicotine-exposed animals were compared with data from 12 saline-exposed animals. Nicotine (6 mg/kg of nicotine tartrate per day) or saline exposure was induced by osmotic minipumps that were implanted subdermally on the fifth day of gestation in Sprague-Dawley Dams. Although both saline- and nicotine-exposed pups gained weight at the same rate throughout the studies, there were subtle differences in ventilatory indices between the two groups. Nicotine-exposed animals had a significantly higher breathing frequency on day 10, and a lower tidal volume on days 14 and 18. Although ventilation tended to be lower in the nicotine-exposed animals, the difference was not significant. There was a significantly higher frequency of apneas in the nicotine-exposed compared with the saline-exposed animals on postnatal days 1 and 2, but the apnea duration did not differ between the groups. No apneas were observed in any of the animals after the sixth postnatal day. Prenatal nicotine exposure is associated with a greater incidence of apneas on the first two postnatal days, and then an altered breathing pattern that manifests at a later stage of development.

Animals↗
PubMed2004

GABAA receptors mediate postnatal depression of respiratory frequency by barbiturates.

We tested the hypothesis that barbiturates depress respiratory motor output by actions on the GABAA receptor. We examined the influence of pentobarbital sodium on nerve activity recorded from a fourth cervical (C4) ventral root (phrenic motoneuron output) in the in vitro brainstem-spinal cord preparation of neonatal rats aged 1-3 days. Bath application of pentobarbital slowed the respiratory rhythm but this effect could be reversed by drug washout or by simultaneous application of 8 microM bicuculline methiodide, a GABAA receptor antagonist. Pentobarbital up to a concentration of 80 microM (or 20 mg/l) did not change the magnitude of C4 nerve bursts. The GABAA receptor agonist muscimol evoked similar changes. The results support the hypothesis that respiratory depression by barbiturates is due to GABAA receptor-mediated inhibition, with the principal effects on rhythm generation. In the light of recent studies suggesting that GABAA receptors may be excitatory in the early neonatal period, we examined postnatal changes in the GABAergic slowing of respiratory rhythm. Stimulation of GABAA receptors slowed respiratory rhythm from the first postnatal day, with no change in efficacy over the first 3 days of life.

Animals↗
PubMed2004

Endurance training of respiratory muscles improves cycling performance in fit young cyclists.

BACKGROUND: Whether or not isolated endurance training of the respiratory muscles improves whole-body endurance exercise performance is controversial, with some studies reporting enhancements of 50% or more, and others reporting no change. Twenty fit (VO2 max 56.0 ml/kg/min), experienced cyclists were randomly assigned to three groups. The experimental group (n = 10) trained their respiratory muscles via 20, 45 min sessions of hyperpnea. The placebo group (n = 4) underwent "sham" training (20, 5 min sessions), and the control group (n = 6) did no training. RESULTS: After training, the experimental group increased their respiratory muscle endurance capacity by 12%. Performance on a bicycle time trial test designed to last about 40 min improved by 4.7% (9 of 10 subjects showed improvement). There were no test-re-test improvements in either respiratory muscle or bicycle exercise endurance performance in the placebo group, nor in the control group. After training, the experimental group had significantly higher ventilatory output and VO2, and lower PCO2, during constant work-rate exercise; the placebo and control groups did not show these changes. The perceived respiratory effort was unchanged in spite of the higher ventilation rate after training. CONCLUSIONS: The results suggest that respiratory muscle endurance training improves cycling performance in fit, experienced cyclists. The relative hyperventilation with no change in respiratory effort sensations suggest that respiratory muscle training allows subjects to tolerate the higher exercise ventilatory response without more dyspnea. Whether or not this can explain the enhanced performance is unknown.

Adolescent↗
PubMed2004

Ventilatory drive and the apnea-hypopnea index in six-to-twelve year old children.

BACKGROUND: We tested the hypothesis that ventilatory drive in hypoxia and hypercapnia is inversely correlated with the number of hypopneas and obstructive apneas per hour of sleep (obstructive apnea hypopnea index, OAHI) in children. METHODS: Fifty children, 6 to 12 years of age were studied. Participants had an in-home unattended polysomnogram to compute the OAHI. We subsequently estimated ventilatory drive in normoxia, at two levels of isocapnic hypoxia, and at three levels of hyperoxic hypercapnia in each subject. Experiments were done during wakefulness, and the mouth occlusion pressure measured 0.1 seconds after inspiratory onset (P0.1) was measured in all conditions. The slope of the relation between P0.1 and the partial pressure of end-tidal O2 or CO2 (PETO2 and PETCO2) served as the index of hypoxic or hypercapnic ventilatory drive. RESULTS: Hypoxic ventilatory drive correlated inversely with OAHI (r = -0.31, P = 0.041), but the hypercapnic ventilatory drive did not (r = -0.19, P = 0.27). We also found that the resting PETCO2 was significantly and positively correlated with the OAHI, suggesting that high OAHI values were associated with resting CO2 retention. CONCLUSIONS: In awake children the OAHI correlates inversely with the hypoxic ventilatory drive and positively with the resting PETCO2. Whether or not diminished hypoxic drive or resting CO2 retention while awake can explain the severity of sleep-disordered breathing in this population is uncertain, but a reduced hypoxic ventilatory drive and resting CO2 retention are associated with sleep-disordered breathing in 6-12 year old children.

Journal Article↗
PubMed2004

Parasomnias and sleep disordered breathing in Caucasian and Hispanic children - the Tucson children's assessment of sleep apnea study.

BACKGROUND: Recent studies in children have demonstrated that frequent occurrence of parasomnias is related to increased sleep disruption, mental disorders, physical harm, sleep disordered breathing, and parental duress. Although there have been several cross-sectional and clinical studies of parasomnias in children, there have been no large, population-based studies using full polysomnography to examine the association between parasomnias and sleep disordered breathing. The Tucson Children's Assessment of Sleep Apnea study is a community-based cohort study designed to investigate the prevalence and correlates of objectively measured sleep disordered breathing (SDB) in pre-adolescent children six to 11 years of age. This paper characterizes the relationships between parasomnias and SDB with its associated symptoms in these children. METHODS: Parents completed questionnaires pertaining to their child's sleep habits. Children had various physiological measurements completed and then were connected to the Compumedics PS-2 sleep recording system for full, unattended polysomnography in the home. A total of 480 unattended home polysomnograms were completed on a sample that was 50% female, 42.3% Hispanic, and 52.9% between the ages of six and eight years. RESULTS: Children with a Respiratory Disturbance Index of one or greater were more likely to have sleep walking (7.0% versus 2.5%, p < 0.02), sleep talking (18.3% versus 9.0%, p < 0.006), and enuresis (11.3% versus 6.3%, p < 0.08) than children with an Respiratory Disturbance Index of less than one. A higher prevalence of other sleep disturbances as well as learning problems was observed in children with parasomnia. Those with parasomnias associated with arousal were observed to have increased number of stage shifts. Small alterations in sleep architecture were found in those with enuresis. CONCLUSIONS: In this population-based cohort study, pre-adolescent school-aged children with SDB experienced more parasomnias than those without SDB. Parasomnias were associated with a higher prevalence of other sleep disturbances and learning problems. Clinical evaluation of children with parasomnias should include consideration of SDB.

Arizona↗
PubMed2003

Clinical outcomes associated with sleep-disordered breathing in Caucasian and Hispanic children--the Tucson Children's Assessment of Sleep Apnea study (TuCASA).

STUDY OBJECTIVES: This report describes clinical outcomes and threshold levels of respiratory disturbance index (RDI) associated with sleep-disordered breathing in children participating in the Tucson Children's Assessment of Sleep Apnea study. DESIGN: A community-based, prospective cohort study designed to assess the severity of sleep-related symptoms associated with sleep-disordered breathing in children aged 6 to 11 years. SETTING: Students attending elementary school in the Tucson Unified School District. PARTICIPANTS: Unattended home polysomnograms were completed on 239 children-55.2% boys, 51% Hispanic, and 55% between the ages of 6 and 8 years. MEASUREMENTS AND RESULTS: Based on full home polysomnography, levels of RDI that correspond to a higher prevalence of clinical symptoms of sleep-disordered breathing in children aged 6 to 11 were observed. An RDI of at least 5 was associated with frequent snoring (20.3% vs 9.1%, P<.01), excessive daytime sleepiness (22.9% vs 10.7%, P<.01), and learning problems (8.5% vs 2.5%, P<.04) when no oxygen desaturation accompanied the respiratory event. An RDI of at least 1 was associated with these symptoms when a 3% oxygen desaturation was required, snoring (24.0% vs 10.4%, P<.006), excessive daytime sleepiness (24.0% vs 13.4%, P<.04), and learning problems (10.7% vs 3.0%, P<.02). Hispanic or Caucasian ethnicity, sex, age category, obesity, insomnia, and witnessed apnea were not associated with RDI regardless of event definition. CONCLUSIONS: The Tucson Children's Assessment of Sleep Apnea study has shown that there are values of RDI based on polysomnography that correspond to an increased rate of clinical symptoms in children ages 6 to 11 years.

Body Mass Index↗
PubMed2003

Pressure-volume behaviour of the rat upper airway: effects of tongue muscle activation.

Our hypothesis was that the simultaneous activation of tongue protrudor and retractor muscles (co-activation) would constrict and stiffen the pharyngeal airway more than the independent activation of tongue protrudor muscles. Upper airway stiffness was determined by injecting known volumes of air into the sealed pharyngeal airway of the anaesthetized rat while measuring nasal pressure under control (no-stimulus) and stimulus conditions (volume paired with hypoglossal (XII) nerve stimulation). Stimulation of the whole XII nerves (co-activation) or the medial XII branches (protrudor activation) effected similar increases in total pharyngeal airway stiffness. Importantly, co-activation produced volume compression (airway narrowing) at large airway volumes (P < 0.05), but had no effect on airway dimension at low airway volumes. In comparison, protrudor activation resulted in significant volume expansion (airway dilatation) at low airway volumes and airway narrowing at high airway volumes (P < 0.05). In conclusion, both co-activation and independent protrudor muscle activation increase airway stiffness. However, their effects on airway size are complex and depend on the condition of the airway at the time of activation.

Air Pressure↗
PubMed2003

Sleep architecture in normal Caucasian and Hispanic children aged 6-11 years recorded during unattended home polysomnography: experience from the Tucson Children's Assessment of Sleep Apnea Study (TuCASA).

OBJECTIVE: To obtain normative sleep architecture data from unattended home polysomnography in Caucasian and Hispanic children aged 6-11 years. DESIGN AND SUBJECTS: Unattended home polysomnography was performed on a single night in Caucasian and Hispanic children aged 6-11 years as part of the Tucson Children's Assessment of Sleep Apnea Study (TuCASA), a cohort study designed to examine the prevalence and correlates of sleep disordered breathing. A subset of 42 children enrolled in TuCASA who had no symptoms of any sleep disorder and had polysomnograms without technical recording problems. RESULTS: Sleep architecture in preadolescent Caucasian and Hispanic children was not different between boys and girls. However, total sleep time (TST), sleep efficiency (SLE) and time spent in REM sleep declined with increasing age. In addition, the number of sleep to wake stage shifts was slightly higher in younger children. Hispanic children had less Stage 3/4 sleep (18+/-1 vs. 22+/-1%, P</=0.02) and correspondingly more Stage 2 sleep (55+/-2 vs. 50.0+/-1%, P</=0.02) than their Caucasian counterparts. CONCLUSIONS: Using unattended home polysomnography, indices of sleep duration and architecture are not different between preadolescent boys and girls. However, with increasing age, TST and SLE decreased. In addition, there are differences in sleep architecture between Caucasians and Hispanics, which may be an important consideration in the evaluation of children with sleep disorders.

Child↗
PubMed2003

Learning in children and sleep disordered breathing: findings of the Tucson Children's Assessment of Sleep Apnea (tuCASA) prospective cohort study.

We examined the relationship between nocturnal respiratory disturbance and learning and compared learning in children with and without nocturnal respiratory disturbance. Subjects were 149 participants in a prospective cohort study examining sleep in children ages 6-12: The Tucson Children's Assessment of Sleep Apnea study (TuCASA). Sleep was assessed via home polysomnography. Intelligence, learning and memory, and academic achievement were assessed. Parents rated attention. Group comparisons were used to test the hypothesis that the group with an apnea/hypopnea index (AHI) of 5 or more (n = 77) would have weaker performance than the group with AHI less than 5 (n = 72). The group with AHI of 5 or more had weaker learning and memory though differences between groups decreased when arousals were taken into account. There was a greater percentage of Stage 1 sleep in the AHI 5 or more group, and Stage 1 percentage was negatively related to learning and memory in the sample (n = 149). There were negative relationships between AHI and immediate recall, Full Scale IQ, Performance IQ, and math achievement. Hypoxemia was associated with lower Performance IQ. Thus, findings suggest that nocturnal respiratory disturbance is associated with decreased learning in otherwise healthy children, that sleep fragmentation adversely impacts learning and memory, and that hypoxemia adversely influences nonverbal skills.

Attention↗
PubMed2002

Respiratory-related activation of human abdominal muscles during exercise.

We tested the hypothesis that abdominal muscles are active during the expiratory phase of the respiratory cycle during exercise. Electromyographic (EMG) activities of external oblique and rectus abdominis muscles were recorded during incremental exercise to exhaustion and during 30 min of constant work rate exercise at an intensity of 85 % of the peak oxygen consumption rate (V(O(2))). High amplitude intramuscular EMG activities of both abdominal muscles could be evoked with postural manoeuvres in all subjects. During cycling, respiratory-related activity of the external obliques was evoked in four of seven subjects, whereas rectus abdominis activity was observed in six of the seven subjects. We measured only the activity that was confined exclusively to the expiratory phase of the respiratory cycle. Expiratory activity of both muscles increased with exercise intensity, although peak values averaged only 10-20 or 20-40 % of the peak activity (obtained during maximal, voluntary expiratory efforts) for the external oblique and rectus abdominis muscles, respectively. To estimate how much of the recorded abdominal muscle activity was supporting leg movements during exercise, we compared the activity at the very end of incremental exercise to that recorded during the first five respiratory cycles after the abrupt cessation of exercise, when ventilation was still very high. Although external oblique activity was reduced after exercise stopped, clear expiratory activity remained. Rectus abdominis activity remained high after exercise cessation, showing a gradual decline that approximated the decline in ventilation. During constant work rate exercise, EMG activities increased to 40-50 and 5-10 % of peak in rectus and external oblique muscles, respectively, and then plateaued for the remainder of the bout in spite of a continual upward drift in (V(O(2))) and pulmonary ventilation. Linear regression analysis showed that the rise in respiratory-related expiratory muscle activity during progressive intensity exercise was significantly correlated with ventilation, although weakly. In constant work rate exercise, expiratory EMG activities increased, but the changes were highly variable and did not change as a function of exercise time, even though ventilation drifted significantly with time. These experiments suggest that abdominal muscles play a role in regulating the ventilatory response to progressive intensity bicycle exercise, although some of the observed activity may support postural adjustments or limb movements. The contribution of abdominal muscles to ventilation during constant work rate exercise is variable, and expiratory activity does not 'drift' significantly with time.

Abdominal Muscles↗
PubMed2002

Mechanisms of force failure during repetitive maximal efforts in a human upper airway muscle.

The upper airway respiratory muscles play an important role in the regulation of airway resistance, but surprisingly little is known about their contractile properties and endurance performance. We developed a technique that allows measurement of force and the electromyogram (EMG) of human nasal dilator muscles (NDMs). Endurance performance was quantified by measuring NDM "flaring" force and EMG activity as healthy human subjects performed 10 s maximal voluntary contractions (MVCs), separated by 10 s rest, until the area under the force curve fell to 50% MVC (the time limit of the fatigue task, Tlim), which was reached in 34.2 +/- 3.1 contractions (685.0 +/- 62.3 s). EMG activity was unchanged except at Tlim, where it averaged 78.7 +/- 3.6% of pretest activity (P < 0.01). M-wave amplitude did not change, suggesting that neuromuscular propagation was not impaired. MVC force increased to 80% of the pretest level within 10 min of recovery but twitch force failed to recover, suggesting low-frequency fatigue. The data suggest that a failure of the nervous system to excite muscle could explain at most only a small fraction of the NDM force loss during an intermittent fatigue task, and then only at Tlim. Thus, the majority of the force failure during this task is due to impairment of mechanisms that reside within the muscle fibers.

Adult↗