Compensatory airway dilation and additive ventilatory augmentation mediated by dorsomedial medullary 5-hydroxytryptamine 2 receptor activity and hypercapnia

2007 ◽  
Vol 293 (2) ◽  
pp. R854-R860 ◽  
Author(s):  
Mitsuko Kanamaru ◽  
Ikuo Homma
Keyword(s):  
Tidal Volume ◽  
Airway Resistance ◽  
Minute Ventilation ◽  
Receptor Activity ◽  
Hypoglossal Nucleus ◽  
Microdialysis Probe ◽  
Airway Narrowing ◽  
Medullary Raphe ◽  
Ly 53857 ◽  
Ventilatory Volume

5-HT2 receptor activity in the hypoglossal nucleus and hypercapnia is associated with airway dilation. 5-HT neurons in the medullary raphe and hypercapnia are responsible for tidal volume change. In this study, the effects of 5-HT2 receptors in the dorsomedial medulla oblongata (DMM), which receives projections from the medullary raphe, and hypercapnia on airway resistance and respiratory variables were studied in mice while monitoring 5-HT release in the DMM. A microdialysis probe was inserted into the DMM of anesthetized adult mice. Each mouse was placed in a double-chamber plethysmograph. After recovery from anesthesia, the mice were exposed to stepwise increases in CO2 inhalation (5%, 7%, and 9% CO2 in O2) at 8-min intervals with a selective serotonin reuptake inhibitor, fluoxetine, or fluoxetine plus a 5-HT2 receptor antagonist, LY-53857 in the DMM. In response to fluoxetine plus LY-53857 coperfusion, specific airway resistance was increased, and tidal volume and minute ventilation were decreased. CO2 inhalation with fluoxetine plus LY-53857 coperfusion in the DMM largely decreased airway resistance and additively increased minute ventilation. Thus, 5-HT2 receptor activity in the DMM increases basal levels of airway dilation and ventilatory volume, dependent on central inspiratory activity and the volume threshold of the inspiratory off-switch mechanism. Hypercapnia with low 5-HT2 receptor activity in the DMM largely recovers airway dilation and additively increases ventilatory volume. Interaction between 5-HT2 receptor activity in the DMM and CO2 drive may elicit a cycle of hyperventilation with airway dilation and hypoventilation with airway narrowing.

Dorsomedial medullary 5-HT2 receptors mediate immediate onset of initial hyperventilation, airway dilation, and ventilatory decline during hypoxia in mice

2009 ◽  
Vol 297 (1) ◽  
pp. R34-R41 ◽  
Author(s):  
Mitsuko Kanamaru ◽  
Ikuo Homma
Keyword(s):  
Periodic Breathing ◽  
Hypoglossal Nucleus ◽  
Solitary Tract ◽  
Microdialysis Probe ◽  
Airway Narrowing ◽  
Obstructive Sleep ◽  
Recovery From Anesthesia ◽  
Airway Responses ◽  
Ly 53857 ◽  
Double Chamber

The dorsomedial medulla oblongata (DMM) includes the solitary tract nucleus and the hypoglossal nucleus, to which 5-HT neurons project. Effects of 5-HT in the DMM on ventilatory augmentation and airway dilation are mediated via 5-HT2 receptors, which interact with the CO2 drive. The interaction may elicit cycles between hyperventilation with airway dilation and hypoventilation with airway narrowing. In the present study, effects of 5-HT2 receptors in the DMM on hypoxic ventilatory and airway responses were investigated, while 5-HT release in the DMM was monitored. Adult male mice were anesthetized, and then a microdialysis probe was inserted into the DMM. The mice were placed in a double-chamber plethysmograph. After recovery from anesthesia, the mice were exposed to hypoxic gas (7% O2 in N2) for 5 min with or without a 5-HT2 receptor antagonist (LY-53857) perfused in the DMM. 5-HT release in the DMM was increased by hypoxia regardless of the presence of LY-53857. Immediate onset and the peak of initial hypoxic hyperventilatory responses were delayed. Subsequent ventilatory decline and airway dilation during initial hypoxic hyperventilation were suppressed with LY-53857. These results suggest that 5-HT release increased by hypoxia acts on 5-HT2 receptors in the DMM, which contributes to the immediate onset of initial hypoxic hyperventilation, airway dilation, and subsequent ventilatory decline. Hypoxic ventilatory and airway responses mediated via 5-HT2 receptors in the DMM may play roles in immediate rescue and defensive adaptation for hypoxia and may be included in periodic breathing and the pathogenesis of obstructive sleep apnea.

Chronic fluoxetine microdialysis into the medullary raphe nuclei of the rat, but not systemic administration, increases the ventilatory response to CO2

2004 ◽  
Vol 97 (5) ◽  
pp. 1763-1773 ◽  
Author(s):  
Natalie C. Taylor ◽  
Aihua Li ◽  
Adam Green ◽  
Hannah C. Kinney ◽  
Eugene E. Nattie
Keyword(s):  
Tidal Volume ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Repeated Administration ◽  
Fluoxetine Treatment ◽  
Artificial Cerebrospinal Fluid ◽  
Medullary Raphe ◽  
Chronic Fluoxetine ◽  
Serotonergic Function ◽  
Ventilatory Response To Co2

In conscious rats, focal CO2 stimulation of the medullary raphe increases ventilation, whereas interference with serotonergic function here decreases the ventilatory response to systemic hypercapnia. We sought to determine whether repeated administration of a selective serotonin reuptake inhibitor in this region would increase the ventilatory response to hypercapnia in unanesthetized rats. In rats instrumented with electroencephalogram-electromyogram electrodes, 250 or 500 μM fluoxetine or artificial cerebrospinal fluid (aCSF) was microdialyzed into the medullary raphe for 30 min daily over 15 days. To compare focal and systemic treatment, two additional groups of rats received 10 mg·kg−1·day−1 fluoxetine or vehicle systemically. Ventilation was measured in normocapnia and in 7% CO2 before treatment ( day 0), acutely ( days 1 or 3), on day 7, and on day 15. There was no change in normocapnic ventilation in any treatment group. Rats that received 250 μM fluoxetine microdialysis showed a significant 13% increase in ventilation in wakefulness during hypercapnia on day 7, due to an increase in tidal volume. In rats microdialyzed with 500 μM fluoxetine, there were 16 and 32% increases in minute ventilation during hypercapnia in wakefulness and sleep on day 7, and 20 and 28% increases on day 15, respectively, again due to increased tidal volume. There was no change in the ventilatory response to CO2 in rats microdialyzed with aCSF or in systemically treated rats. Chronic fluoxetine treatment in the medullary raphe increases the ventilatory response to hypercapnia in an unanesthetized rat model, an effect that may be due to facilitation of chemosensitive serotonergic neurons.

Distribution of airway narrowing during hyperpnea-induced bronchoconstriction in guinea pigs

1990 ◽  
Vol 69 (4) ◽  
pp. 1323-1329 ◽  
Author(s):  
D. W. Ray ◽  
S. Eappen ◽  
C. Hernandez ◽  
M. Jackson ◽  
L. E. Alger ◽  
...  
Keyword(s):  
Tidal Volume ◽  
Guinea Pigs ◽  
Minute Ventilation ◽  
Main Stem ◽  
Water Losses ◽  
Airway Narrowing ◽  
Local Stimulus ◽  
Isocapnic Hyperpnea

Increasing minute ventilation of dry gas shifts the principal burden of respiratory heat and water losses from more proximal airway to airways farther into the lung. If these local thermal transfers determine the local stimulus for bronchoconstriction, then increasing minute ventilation of dry gas might also extend the zone of airway narrowing farther into the lung during hyperpnea-induced bronchoconstriction (HIB). We tested this hypothesis by comparing tantalum bronchograms in tracheostomized guinea pigs before and during bronchoconstriction induced by dry gas hyperpnea, intravenous methacholine, and intravenous capsaicin. In eight animals subjected to 5 min of dry gas isocapnic hyperpnea [tidal volume (VT) = 2-5 ml, 150 breaths/min], there was little change in the diameter of the trachea or the main stem bronchi up to 0.75 cm past the main carina (zone 1). In contrast, bronchi from 0.75 to 1.50 cm past the main carina (zone 2) narrowed progressively at all minute ventilations greater than or equal to 300 ml/min (VT = 2 ml). More distal bronchi (1.50-3.10 cm past the main carina; zone 3) did not narrow significantly until minute ventilation was raised to 450 ml/min (VT = 3 ml). The estimated VT during hyperpnea needed to elicit a 50% reduction in airway diameter was significantly higher in zone 3 bronchi [4.3 +/- 0.8 (SD) ml] than in zone 2 bronchi (3.5 +/- 1.1 ml, P less than 0.012).(ABSTRACT TRUNCATED AT 250 WORDS)

Respiratory muscle activity during sleep-induced periodic breathing in the elderly

1994 ◽  
Vol 77 (5) ◽  
pp. 2285-2290 ◽  
Author(s):  
D. W. Hudgel ◽  
H. B. Hamilton
Keyword(s):  
Tidal Volume ◽  
Airway Resistance ◽  
Minute Ventilation ◽  
Upper Airway ◽  
Periodic Breathing ◽  
Nrem Sleep ◽  
The Elderly ◽  
Elderly Subjects ◽  
Upper Airway Resistance ◽  
The Relationship

During spontaneous sleep-induced periodic breathing in elderly subjects, we have found that tidal volume oscillations are related to reciprocal oscillations in upper airway resistance. The purpose of this study was to address the mechanism of the relationship between oscillations in tidal volume and upper airway resistance in elderly subjects with sleep-induced periodic breathing. We hypothesized that the spontaneous periodic breathing observed in non-rapid-eye-movement (NREM) sleep in elderly subjects would be closely related to fluctuations in upper airway resistance and not to changes in central motor drive to ventilatory pump muscles. Therefore, in eight healthy elderly subjects, we measured costal margin chest wall peak moving time average electrical inspiratory activity (CW EMG), ventilation variables, and upper airway resistance during sleep. Five of eight subjects had significant sine wave oscillations in upper airway resistance and tidal volume. For these five subjects, there was a reciprocal exponential relationship between peak upper airway inspiratory resistance and tidal volume or minute ventilation [r = -0.60 +/- 0.20 (SD) (P < 0.05) and -0.55 +/- 0.26 (P < 0.05), respectively], such that as resistance increased, ventilation decreased. The relationship between CW EMG and tidal volume or minute ventilation was quite low (r = 0.12 +/- 0.32 and -0.07 +/- 0.27, respectively). This study demonstrated that oscillations in ventilation during NREM sleep in elderly subjects were significantly related to fluctuations in upper airway resistance but were not related to changes in chest wall muscle electrical activity. Therefore, changes in upper airway caliber likely contribute to oscillations in ventilation seen during sleep-induced periodic breathing in the elderly.

Ventilatory response to hypoxia in unanesthetized newborn kittens

1988 ◽  
Vol 64 (6) ◽  
pp. 2544-2551 ◽  
Author(s):  
H. Rigatto ◽  
C. Wiebe ◽  
C. Rigatto ◽  
D. S. Lee ◽  
D. Cates
Keyword(s):  
Tidal Volume ◽  
Chest Wall ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
Respiratory Frequency ◽  
Quiet Sleep ◽  
Newborn Kitten ◽  
Peripheral Mechanism ◽  
Flow Through ◽  
Ventilatory Response To Hypoxia

We studied the ventilatory response to hypoxia in 11 unanesthetized newborn kittens (n = 54) between 2 and 36 days of age by use of a flow-through system. During quiet sleep, with a decrease in inspired O2 fraction from 21 to 10%, minute ventilation increased from 0.828 +/- 0.029 to 1.166 +/- 0.047 l.min-1.kg-1 (P less than 0.001) and then decreased to 0.929 +/- 0.043 by 10 min of hypoxia. The late decrease in ventilation during hypoxia was related to a decrease in tidal volume (P less than 0.001). Respiratory frequency increased from 47 +/- 1 to 56 +/- 2 breaths/min, and integrated diaphragmatic activity increased from 14.9 +/- 0.9 to 20.2 +/- 1.4 arbitrary units; both remained elevated during hypoxia (P less than 0.001). Younger kittens (less than 10 days) had a greater decrease in ventilation than older kittens. These results suggest that the late decrease in ventilation during hypoxia in the newborn kitten is not central but is due to a peripheral mechanism located in the lungs or respiratory pump and affecting tidal volume primarily. We speculate that either pulmonary bronchoconstriction or mechanical uncoupling of diaphragm and chest wall may be involved.

Decreased Carbon Dioxide Sensitivity in Infants of Substance-Abusing Mothers

PEDIATRICS ◽  
1995 ◽  
Vol 95 (6) ◽  
pp. 864-867
Author(s):  
Janet G. Wingkun ◽  
Janet S. Knisely ◽  
Sidney H. Schnoll ◽  
Gary R. Gutcher
Keyword(s):  
Carbon Dioxide ◽  
Tidal Volume ◽  
Minute Ventilation ◽  
Demographic Data ◽  
Substance Abusing ◽  
Quiet Sleep ◽  
Co2 Level ◽  
The Difference ◽  
End Tidal ◽  
Drug Free

Objective. To determine whether there is a demonstrable abnormality in control of breathing in infants of substance-abusing mothers during the first few days of life. Methods. We enrolled 12 drug-free control infants and 12 infants of substance abusing mothers (ISAMs). These infants experienced otherwise uncomplicated term pregnancies and deliveries. The infants were assigned to a group based on the results of maternal histories and maternal and infant urine toxicology screens. Studies were performed during quiet sleep during the first few days of life. We measured heart rate, oxygen saturations via a pulse oximeter, end-tidal carbon dioxide (ET-CO2) level, respiratory rate, tidal volume, and airflow. The chemoreceptor response was assessed by measuring minute ventilation and the ET-CO2 level after 5 minutes of breathing either room air or 4% carbon dioxide. Results. The gestational ages by obstetrical dating and examination of the infants were not different, although birth weights and birth lengths were lower in the group of ISAMs. Other demographic data were not different, and there were no differences in the infants' median ages at the time of study or in maternal use of tobacco and alcohol. The two groups had comparable baseline (room air) ET-CO2 levels, respiratory rates, tidal volumes, and minute ventilation. When compared with the group of ISAMs, the drug-free group had markedly increased tidal volume and minute ventilation on exposure to 4% carbon dioxide. These increases accounted for the difference in sensitivity to carbon dioxide, calculated as the change in minute ventilation per unit change in ET-CO2 (milliliters per kg/min per mm Hg). The sensitivity to carbon dioxide of control infants was 48.66 ± 7.14 (mean ± SE), whereas that of ISAMs was 16.28 ± 3.14. Conclusions. These data suggest that ISAMs are relatively insensitive to challenge by carbon dioxide during the first few days of life. We speculate that this reflects an impairment of the chemoreceptor response.

Positive Expiratory Pressure: A Potential Therapy to Mitigate Acute Bronchoconstriction in the Asthma of Obesity

2021 ◽  
Author(s):  
Swati a. Bhatawadekar ◽  
Anne E. Dixon ◽  
Ubong Peters ◽  
Nirav Daphtary ◽  
Kevin Hodgdon ◽  
...  
Keyword(s):  
Airway Resistance ◽  
Late Onset ◽  
Rescue Therapy ◽  
Pharmacologic Therapy ◽  
Airway Closure ◽  
Airway Narrowing ◽  
Asthma Patients ◽  
Peripheral Airway ◽  
Central Airway ◽  
Positive Expiratory Pressure

Late-onset non-allergic (LONA) asthma in obesity is characterized by increased peripheral airway closure secondary to abnormally collapsible airways. We hypothesized that positive expiratory pressure (PEP) would mitigate the tendency to airway closure during bronchoconstriction, potentially serving as rescue therapy for LONA asthma of obesity. The PC20 dose of methacholine was determined in 18 obese participants with LONA asthma. At each of 4 subsequent visits, we used oscillometry to measure input respiratory impedance (Zrs) over 8 minutes; participants received their PC20 concentration of methacholine aerosol during the first 4.5 minutes. PEP combinations of either 0 or 10 cmH2O either during and/or after the methacholine delivery were applied, randomized between visits. Parameters characterizing respiratory system mechanics were extracted from the Zrs spectra. In 18 LONA asthma patients (14 females, BMI: 39.6±3.4 kg/m2), 10 cmH2O PEP during methacholine reduced elevations in the central airway resistance, peripheral airway resistance and elastance, and breathing frequency was also reduced. During the 3.5 min following methacholine delivery, PEP of 10 cmH2O reduced Ax and peripheral elastance compared to no PEP. PEP mitigates the onset of airway narrowing brought on by methacholine challenge, and airway closure once it is established. PEP thus might serve as a non-pharmacologic therapy to manage acute airway narrowing for obese LONA asthma.

Effect of sleep on nocturnal bronchoconstriction and ventilatory patterns in asthmatics

1989 ◽  
Vol 67 (1) ◽  
pp. 243-249 ◽  
Author(s):  
R. D. Ballard ◽  
M. C. Saathoff ◽  
D. K. Patel ◽  
P. L. Kelly ◽  
R. J. Martin
Keyword(s):  
Airway Resistance ◽  
Minute Ventilation ◽  
The Other ◽  
Lower Airway ◽  
Sleep Laboratory ◽  
Sleep State ◽  
Asthmatic Patients ◽  
Ventilatory Responses ◽  
Rate Of Increase ◽  
Normal Controls

To assess the effect of sleep on airflow resistance and patterns of ventilation in asthmatic patients with nocturnal worsening, 10 adult subjects (6 asthmatic patients with nocturnal worsening, 4 normal controls) were monitored overnight in the sleep laboratory on two separate occasions. During 1 night, subjects were allowed to sleep normally, whereas during the other night all sleep was prevented. The six asthmatic patients demonstrated progressive increases in lower airway resistance (Rla) on both nights, but the rate of increase was twofold greater (P less than 0.0001) during the sleep night compared with the sleep prevention night. However, overnight decrements in forced expired volume in 1 s (FEV1) were similar over the 2 nights. The asthmatic patients maintained their minute ventilation as Rla increased during sleep, demonstrating a stable tidal volume with a mild increase in respiratory frequency. We conclude that in asthmatic patients with nocturnal worsening 1) Rla increases and FEV1 falls overnight regardless of sleep state, 2) sleep enhances the observed overnight increases in Rla, and 3) sleep does not abolish compensatory ventilatory responses to spontaneously occurring bronchoconstriction.

scholarly journals Impact of cervical spinal cord contusion on the breathing pattern across the sleep-wake cycle in the rat

2019 ◽  
Vol 126 (1) ◽  
pp. 111-123 ◽  
Author(s):  
Kun-Ze Lee
Keyword(s):  
Spinal Cord ◽  
Tidal Volume ◽  
Spinal Injury ◽  
Cervical Spinal Cord ◽  
Minute Ventilation ◽  
Respiratory Frequency ◽  
Breathing Patterns ◽  
Cord Injury ◽  
Spinal Contusion ◽  
Cervical Spinal Injury

The present study was designed to investigate breathing patterns across the sleep-wake state following a high cervical spinal injury in rats. The breathing patterns (e.g., respiratory frequency, tidal volume, and minute ventilation), neck electromyogram, and electroencephalography of unanesthetized adult male rats were measured at the acute (i.e., 1 day), subchronic (i.e., 2 wk), and/or chronic (i.e., 6 wk) injured stages after unilateral contusion of the second cervical spinal cord. Cervical spinal cord injury caused a long-term reduction in the tidal volume but did not influence the sleep-wake cycle duration. The minute ventilation during sleep was usually lower than that during the wake period in uninjured animals due to a decrease in respiratory frequency. However, this sleep-induced reduction in respiratory frequency was not observed in contused animals at the acute injured stage. By contrast, the tidal volume was significantly lower during sleep in contused animals but not uninjured animals from the acute to the chronic injured stage. Moreover, the frequency of sigh and postsigh apnea was elevated in acutely contused animals. These results indicated that high cervical spinal contusion is associated with exacerbated sleep-induced attenuation of the tidal volume and higher occurrence of sleep apnea, which may be detrimental to respiratory functional recovery after cervical spinal cord injury. NEW & NOTEWORTHY Cervical spinal injury is usually associated with sleep-disordered breathing. The present study investigated breathing patterns across sleep-wake state following cervical spinal injury in the rat. Unilateral cervical spinal contusion significantly impacted sleep-induced alteration of breathing patterns, showing a blunted frequency response and exacerbated attenuated tidal volume and occurrence of sleep apnea. The result enables us to investigate effects of cervical spinal injury on the pathogenesis of sleep-disordered breathing and evaluate potential therapies to improve respiration.

Effects of nasal positive-pressure hyperventilation on the glottis in normal awake subjects

1995 ◽  
Vol 79 (1) ◽  
pp. 176-185 ◽  
Author(s):  
V. Jounieaux ◽  
G. Aubert ◽  
M. Dury ◽  
P. Delguste ◽  
D. O. Rodenstein
Keyword(s):  
Tidal Volume ◽  
Positive Pressure Ventilation ◽  
Anterior Commissure ◽  
Minute Ventilation ◽  
Intermittent Positive Pressure Ventilation ◽  
Positive Pressure ◽  
Vocal Cords ◽  
Diaphragmatic Muscle ◽  
Inspiratory Resistance ◽  
Cyclic Changes

We have recently observed obstructive apneas during nasal intermittent positive-pressure ventilation (nIPPV) and suggested that they were due to hypocapnia-induced glottic closure. To confirm this hypothesis, we studied seven healthy subjects and submitted them to nIPPV while their glottis was continuously monitored through a fiber-optic bronchoscope. During wakefulness, we measured breath by breath the widest inspiratory angle formed by the vocal cords at the anterior commissure along with several other indexes. Mechanical ventilation was progressively increased up to 30 l/min. In the absence of diaphragmatic activity, increases in delivered minute ventilation resulted in progressive narrowing of the vocal cords, with an increase in inspiratory resistance and a progressive reduction in the percentage of the delivered tidal volume effectively reaching the lungs. Adding CO2 to the inspired gas led to partial widening of the glottis in two of three subjects. Moreover, activation of the diaphragmatic muscle was always associated with a significant inspiratory abduction of the vocal cords. Sporadically, complete adduction of the vocal cords was directly responsible for obstructive laryngeal apneas and cyclic changes in the glottic aperture resulted in waxing and waning of tidal volume. We conclude that in awake humans passive ventilation with nIPPV results in vocal cord adduction that depends partly on hypocapnia, but our results suggest that other factors may also influence glottic width.

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