Maturational effect of enkephalin on respiratory control in newborn rabbits

The respiratory responses to systemic infusion of the opioid peptide, [D-Ala2, D-Leu5]enkephalin (ENK) were determined in 39 unanesthetized tracheotomized rabbits (age range 1–20 days). At all ages, ventilation (VE), measured in a body plethysmograph, was depressed after ENK infusion in association with a decrease in CO2 elimination (VCO2) and body temperature. The degree of VE depression varied inversely with increasing age and was directly related to changes in mean inspiratory flow (i.e., VT/TI) while the ratio of inspiratory to total breath duration (TI/TT) was unaltered, except in rabbits under about 1 wk of age. Maturational differences in the VE response to ENK were related to age-dependent variation in the stability of the central inspiratory activity, which was manifested as periodic breathing with apnea in rabbits under about 5 days of age. Since the initial inspiratory volume-time profile was little affected by ENK and vagal afferent influence on respiration was not diminished, the depression in VE could be explained by an inhibition of the central inspiratory “off-switch” threshold and delay in central inspiratory “on-switching.” All effects of ENK were reversed by the opiate antagonist, naloxone.

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Apnea and periodic breathing in bed-sharing and solitary sleeping infants

Journal of Applied Physiology ◽

10.1152/jappl.1998.84.4.1374 ◽

1998 ◽

Vol 84 (4) ◽

pp. 1374-1380 ◽

Cited By ~ 16

Author(s):

Christopher A. Richard ◽

Sarah S. Mosko ◽

James J. McKenna

Keyword(s):

Respiratory Control ◽

Random Order ◽

Periodic Breathing ◽

Developmental Differences ◽

Behavioral Effects ◽

Sleep Laboratory ◽

Physiological Effects ◽

Central Apnea ◽

Bed Sharing

Mother-infant bed sharing, compared with the solitary sleeping condition, has recently been associated with several physiological and behavioral effects. Because the physiological effects of bed sharing may also include respiratory changes, we compared the incidence of central and obstructive apneas and periodic breathing in bed-sharing and solitary sleeping infants. Twenty routinely bed-sharing mother-infant pairs and fifteen routinely solitary sleeping pairs slept for 3 nights in a sleep laboratory. After an initial adaptation night, each pair spent 1 night bed sharing and 1 night in solitary sleep in random order. Apnea and periodic breathing were scored from polysomnographic recordings. The frequency of central apnea was significantly increased on the bed-sharing night, compared with the solitary night, regardless of routine sleeping arrangement. There were significantly fewer obstructive apneas on the bed-sharing night than on the solitary night, but only in routinely solitary sleeping infants. In both groups, there was a significantly higher frequency of periodic breathing events on the bed-sharing night than on the solitary night. These findings demonstrate that the bed-sharing environment can have a significant impact on respiratory control in the infant. Evidence is also presented to suggest that routine bed sharing may result in subtle neurophysiological and/or developmental differences in infants.

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Stabilizing immature breathing patterns of preterm infants using stochastic mechanosensory stimulation

Journal of Applied Physiology ◽

10.1152/japplphysiol.00058.2009 ◽

2009 ◽

Vol 107 (4) ◽

pp. 1017-1027 ◽

Cited By ~ 52

Author(s):

Elisabeth Bloch-Salisbury ◽

Premananda Indic ◽

Frank Bednarek ◽

David Paydarfar

Keyword(s):

Preterm Infants ◽

Respiratory Control ◽

Behavioral State ◽

Mean Square ◽

Breathing Patterns ◽

Nonlinear Properties ◽

Improved Stability ◽

Postconceptional Age ◽

The Stability ◽

Large Improvement

Breathing patterns in preterm infants consist of highly variable interbreath intervals (IBIs) that might originate from nonlinear properties of the respiratory oscillator and its input-output responses to peripheral and central signals. Here, we explore a property of nonlinear control, the potential for large improvement in the stability of breathing using low-level exogenous stochastic stimulation. Stimulation was administered to 10 preterm infants (postconceptional age: mean 33.3 wk, SD 1.7) using a mattress with embedded actuators that delivered small stochastic displacements (0.021 mm root mean square, 0.090 mm maximum, 30–60 Hz); this stimulus was subthreshold for causing arousal from sleep to wakefulness or other detectable changes in the behavioral state evaluated with polysomnography. We used a test-retest protocol with multiple 10-min intervals of stimulation, each paired with 10-min intervals of no stimulation. Stimulation induced an ∼50% reduction ( P = 0.003) in the variance of IBIs and an ∼50% reduction ( P = 0.002) in the incidence of IBIs > 5 s. The improved stability of eupneic breathing was associated with an ∼65% reduction ( P = 0.04) in the duration of O2 desaturation. Our findings suggest that nonlinear properties of the immature respiratory control system can be harnessed using afferent stimuli to stabilize eupneic breathing, thereby potentially reducing the incidence of apnea and hypoxia.

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Periodic breathing in the mouse

Journal of Applied Physiology ◽

10.1152/japplphysiol.00785.2001 ◽

2002 ◽

Vol 92 (3) ◽

pp. 1133-1140 ◽

Cited By ~ 57

Author(s):

Fang Han ◽

Shyam Subramanian ◽

Edwin R. Price ◽

Joseph Nadeau ◽

Kingman P. Strohl

Keyword(s):

Recombinant Inbred ◽

Periodic Breathing ◽

Inbred Strains ◽

Genetic Influences ◽

Short Term ◽

Cycle Number ◽

Term Potentiation ◽

Genetic Mechanisms ◽

The Stability ◽

Recombinant Mice

The hypothesis was that unstable breathing might be triggered by a brief hypoxia challenge in C57BL/6J (B6) mice, which in contrast to A/J mice are known not to exhibit short-term potentiation; as a consequence, instability of ventilatory behavior could be inherited through genetic mechanisms. Recordings of ventilatory behavior by the plethsmography method were made when unanesthetized B6 or A/J animals were reoxygenated with 100% O2 or air after exposure to 8% O2 or 3% CO2-10% O2 gas mixtures. Second, we examined the ventilatory behavior after termination of poikilocapnic hypoxia stimuli in recombinant inbred strains derived from B6 and A/J animals. Periodic breathing (PB) was defined as clustered breathing with either waxing and waning of ventilation or recurrent end-expiratory pauses (apnea) of ≥2 average breath durations, each pattern being repeated with a cycle number ≥3. With the abrupt return to room air from 8% O2, 100% of the 10 B6 mice exhibited PB. Among them, five showed breathing oscillations with apnea, but none of the 10 A/J mice exhibited cyclic oscillations of breathing. When the animals were reoxygenated after 3% CO2-10% O2 challenge, no PB was observed in A/J mice, whereas conditions still induced PB in B6 mice. (During 100% O2 reoxygenation, all 10 B6 mice had PB with apnea.) Expression of PB occurred in some but not all recombinant mice and was not associated with the pattern of breathing at rest. We conclude that differences in expression of PB between these strains indicate that genetic influences strongly affect the stability of ventilation in the mouse.

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Incidence of Apnea in Siblings of Sudden Infant Death Syndrome Victims Studied at Home

PEDIATRICS ◽

10.1542/peds.70.1.128 ◽

1982 ◽

Vol 70 (1) ◽

pp. 128-131

Author(s):

Dorothy H. Kelly ◽

Joseph Twanmoh ◽

Daniel C. Shannon

Keyword(s):

Sudden Infant Death Syndrome ◽

Infant Death ◽

Chronic Hypoxia ◽

Breathing Pattern ◽

Respiratory Control ◽

Periodic Breathing ◽

Sudden Infant Death ◽

Near Miss ◽

Sudden Infant ◽

Sibling Group

Victims of sudden infant death syndrome (SIDS) have been shown to have pathologic abnormalities consistent with chronic hypoxia.1-7 Two groups of infants at high risk of dying of SIDS, near miss infants and subsequent siblings of SIDS victims, have been studied in attempts to demonstrate physiologic abnormalities that could account for these pathologic findings. Investigators have found abnormalities in breathing pattern and the respiratory control system in the former consisting of prolonged sleep apnea, excessive short apnea, periodic breathing, hypoventilation, and depressed response to hypercarbia.8-13 However, studies in the SIDS sibling group have demonstrated varying results of excessive periodic breathing in the home14 and decreased apnea in the laboratory.15

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Relative stability of human respiration during progressive hypoxia

Journal of Applied Physiology ◽

10.1152/jappl.1988.65.3.1389 ◽

1988 ◽

Vol 65 (3) ◽

pp. 1389-1399 ◽

Cited By ~ 21

Author(s):

D. W. Carley ◽

D. C. Shannon

Keyword(s):

Mathematical Model ◽

Control System ◽

Relative Stability ◽

Respiratory Control ◽

Periodic Breathing ◽

Adult Males ◽

Human Respiration ◽

Progressive Hypoxia ◽

The Mean ◽

Breathing Room

We have systematically studied the relationship between the relative stability (R) of respiration and the loop gain (LG) of the CO2 control system in 15 healthy awake adult males during progressive hypoxia. R was measured by the ventilatory oscillations after brief (less than 10 s) CO2 challenges. Control theory suggests that such oscillations are completely governed by LG. A significant positive correlation was found between R and LG (r = 0.74, P less than 0.01, n = 85). A minimal mathematical model of respiratory control was used to predict R as a function of LG. Serial correlation analysis (r = 0.09, P greater than 0.1) of the residuals indicated statistical agreement between predictions and observations. The mean residual (0.011) was not significantly different from zero (P greater than 0.1). Also, as the model predicted, sustained periodic breathing (PB) occurred whenever the estimated LG was greater than unity. The mean LG breathing room air was 0.51 and for the 13 epochs of PB was 1.17 (range 0.71-1.65). It is concluded that PB is a quantitative extension of the relative stability continuum and corresponds to unstable operation of the CO2 control system. Furthermore, relative stability can be quantitatively predicted for each subject by a minimal mathematical model.

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Possible mechanisms of periodic breathing during sleep

Journal of Applied Physiology ◽

10.1152/jappl.1988.64.3.1000 ◽

1988 ◽

Vol 64 (3) ◽

pp. 1000-1008 ◽

Cited By ~ 47

Author(s):

K. R. Chapman ◽

E. N. Bruce ◽

B. Gothe ◽

N. S. Cherniack

Keyword(s):

Control System ◽

Respiratory Control ◽

Periodic Breathing ◽

Nrem Sleep ◽

Loop Gain ◽

Hypoxic Conditions ◽

Spontaneous Oscillations ◽

End Tidal ◽

Arterial O2 Saturation ◽

Stage 1

To determine the effect of respiratory control system loop gain on periodic breathing during sleep, 10 volunteers were studied during stage 1-2 non-rapid-eye-movement (NREM) sleep while breathing room air (room air control), while hypoxic (hypoxia control), and while wearing a tight-fitting mask that augmented control system gain by mechanically increasing the effect of ventilation on arterial O2 saturation (SaO2) (hypoxia increased gain). Ventilatory responses to progressive hypoxia at two steady-state end-tidal PCO2 levels and to progressive hypercapnia at two levels of oxygenation were measured during wakefulness as indexes of controller gain. Under increased gain conditions, five male subjects developed periodic breathing with recurrent cycles of hyperventilation and apnea; the remaining subjects had nonperiodic patterns of hyperventilation. Periodic breathers had greater ventilatory response slopes to hypercapnia under either hyperoxic or hypoxic conditions than nonperiodic breathers (2.98 ± 0.72 vs. 1.50 ± 0.39 l.min-1.Torr-1; 4.39 ± 2.05 vs. 1.72 ± 0.86 l.min-1.Torr-1; for both, P less than 0.04) and greater ventilatory responsiveness to hypoxia at a PCO2 of 46.5 Torr (2.07 ± 0.91 vs. 0.87 ± 0.38 l.min-1.% fall in SaO2(-1); P less than 0.04). To assess whether spontaneous oscillations in ventilation contributed to periodic breathing, power spectrum analysis was used to detect significant cyclic patterns in ventilation during NREM sleep. Oscillations occurred more frequently in periodic breathers, and hypercapnic responses were higher in subjects with oscillations than those without. The results suggest that spontaneous oscillations in ventilation are common during sleep and can be converted to periodic breathing with apnea when loop gain is increased.

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Control of Respiratory Motion by Hypnosis Intervention during Radiotherapy of Lung Cancer I

BioMed Research International ◽

10.1155/2013/574934 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Rongmao Li ◽

Jie Deng ◽

Yaoqin Xie

Keyword(s):

Lung Cancer ◽

Normal State ◽

Respiratory Motion ◽

Lung Tumor ◽

Respiratory Control ◽

Image Guided Radiotherapy ◽

Control Scheme ◽

Wide Range ◽

The Stability ◽

Respiration Motion

The uncertain position of lung tumor during radiotherapy compromises the treatment effect. To effectively control respiratory motion during radiotherapy of lung cancer without any side effects, a novel control scheme, hypnosis, has been introduced in lung cancer treatment. In order to verify the suggested method, six volunteers were selected with a wide range of distribution of age, weight, and chest circumference. A set of experiments have been conducted for each volunteer, under the guidance of the professional hypnotist. All the experiments were repeated in the same environmental condition. The amplitude of respiration has been recorded under the normal state and hypnosis, respectively. Experimental results show that the respiration motion of volunteers in hypnosis has smaller and more stable amplitudes than in normal state. That implies that the hypnosis intervention can be an alternative way for respiratory control, which can effectively reduce the respiratory amplitude and increase the stability of respiratory cycle. The proposed method will find useful application in image-guided radiotherapy.

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Temperature and CO2 effect on phrenic activity and tracheal occlusion pressure

Journal of Applied Physiology ◽

10.1152/jappl.1977.43.3.449 ◽

1977 ◽

Vol 43 (3) ◽

pp. 449-454 ◽

Cited By ~ 10

Author(s):

T. Trippenbach ◽

J. Milic-Emili

Keyword(s):

Body Temperature ◽

Moving Average ◽

Similar Increase ◽

Occlusion Pressure ◽

Tracheal Occlusion ◽

Pentobarbital Sodium ◽

Central Inspiratory Activity ◽

Similar Index ◽

Inspiratory Activity ◽

Breathing Room

The present investigation was undertaken to study the interaction of CO2 and body temperature on phrenic activity (moving average) and tracheal occlusion pressure. Studies were performed on spontaneously ventilated cats anesthetized with pentobarbital sodium at different body temperatures (32–41 degrees C) while breathing room air, 2 and 4% CO2 in 50% O2. At any given chemical drive, increased body temperature caused a similar increase in rate of phrenic activity and tracheal occlusion pressure, while their peak values remained virtually unchanged. At any given body temperature, increased chemical drive caused an increase in both rate of rise and peak values of phrenic activity and tracheal occlusion pressure. These results confirm previous findings that body temperature affects the rate of rise of the central inspiratory activity (CIA), but not the inspiratory “off-switch” threshold, while CO2 increases both the rate of rise of CIA and off-switch threshold. In addition the results indicate that tracheal occlusion pressure provides a similar index of CIA as “integrated” phrenic activity.

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