CO2 microdialysis in retrotrapezoid nucleus of the rat increases breathing in wakefulness but not in sleep

1999 ◽  
Vol 87 (3) ◽  
pp. 910-919 ◽  
Author(s):  
Aihua Li ◽  
Margaret Randall ◽  
Eugene E. Nattie
Keyword(s):  
Control System ◽  
Respiratory Control ◽  
Semipermeable Membrane ◽  
Ph Change ◽  
Microdialysis Probe ◽  
Retrotrapezoid Nucleus ◽  
Central Chemoreceptors ◽  
End Tidal ◽  
The Brain ◽  
Behavioral Criteria

Central chemoreceptors are widespread within the brain stem. We suggest that their function at some sites may vary with the state of arousal. In this study, we tested the hypothesis that the function of chemoreceptors in the retrotrapezoid nucleus (RTN) varies with sleep and wakefulness. In unanesthetized rats, we produced focal acidification of the RTN by means of a microdialysis probe (tip containing the semipermeable membrane = 1-mm length, 240-μm diameter, and 45-nl volume). With the use of a dialysate equilibrated with 25% CO2, the tissue pH change (measured in anesthetized animals) was 1) limited to within 550 μm of the probe and, 2) at the probe tip, was equivalent to that observed with end-tidal[Formula: see text] of 63 Torr. This focal acidification of the RTN increased ventilation significantly by 24% above baseline, on average, in 13 trials in seven rats only during wakefulness. The effect was entirely due to an increase in tidal volume. During sleep defined by behavioral criteria, ventilation was unaffected, on average, in 10 trials in seven rats. During sleep, the chemoreceptors in the RTN appear to be inactive, or, if active, the respiratory control system either is not responding or is responding with very low gain. Because ventilation is increased during sleep with all central chemoreceptor sites stimulated via systemic CO2 application, other central chemoreceptor locations must have enhanced effectiveness.

Possible mechanisms of periodic breathing during sleep

1988 ◽  
Vol 64 (3) ◽  
pp. 1000-1008 ◽  
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.

Basic Oscillating Mechanism of Cheyne-Stokes Breathing

1956 ◽  
Vol 187 (2) ◽  
pp. 395-398 ◽  
Author(s):  
Arthur C. Guyton ◽  
Jack W. Crowell ◽  
John W. Moore
Keyword(s):  
Carbon Dioxide ◽  
Control System ◽  
Transit Time ◽  
Perfusion Pressure ◽  
Respiratory Control ◽  
Delay System ◽  
Carbon Dioxide Concentrations ◽  
Respiratory Centers ◽  
Cheyne Stokes Breathing ◽  
The Brain

Cheyne-Stokes breathing has been induced in 30 dogs by inserting a circulatory delay system between the heart and the brain to prolong the transit time of blood from the lungs to the brain. The duration of each cycle of Cheyne-Stokes breathing increased proportionately with the volume of the delay system and decreased as the perfusion pressure to the brain was increased. Periodic variations in oxygen and carbon dioxide concentrations in the blood were found to be in appropriate phase to stimulate the respiratory centers at the time of maximal ventilation. This supports the theory that Cheyne-Stokes breathing is due to oscillation of the respiratory control system.

Rapid and transient excitation of respiration mediated by central chemoreceptor

1988 ◽  
Vol 64 (4) ◽  
pp. 1369-1375 ◽  
Author(s):  
H. Arita ◽  
N. Kogo ◽  
K. Ichikawa
Keyword(s):  
Control System ◽  
Dynamic Properties ◽  
Respiratory Rhythm ◽  
Respiratory Control ◽  
Facilitatory Effect ◽  
Onset Latency ◽  
Central Chemoreceptors ◽  
Spontaneously Breathing ◽  
Respiratory Phases ◽  
Stimulation Of

We evaluated rapid and transient changes in phrenic nerve (PN) and internal intercostal (IIC) activities when 0.2-0.5 ml of saline saturated with 100% CO2 was injected into the vertebral artery during various respiratory phases in decerebrated spontaneously breathing cats. The injections evoked an initial transient inhibition of ongoing PN or IIC activity with a mean onset latency of 0.17 s, followed by excitation of subsequent respiratory activities with an onset latency ranging from 0.4 to 2.7 s; the average onset latency of expiratory excitation (1.49 s) was significantly longer than that of inspiratory facilitation (0.89 s). The initial inhibitory responses were analogous to reflex effects of injections of phenyl biguanide, indicating that the initial inhibition was due to activation of vascular nociceptors and the subsequent excitation was due to stimulation of the central chemoreceptors. In addition, CO2-saline injections during hypocapnic apnea developed a quick reappearance of respiratory rhythm, and the first facilitatory effect appeared in tonic IIC activity, which became more active before rhythm started. In summary, the present study, by use of a technique of vertebral arterial injections of 100% CO2-saline, revealed dynamic properties of respiratory control system mediated by central chemoreceptors and vascular nociceptors.

Respiratory Control During Exercise: Hormones, Osmolality, Strong Ions, and Paco2

1994 ◽  
Vol 19 (3) ◽  
pp. 334-349 ◽  
Author(s):  
Donald B. Jennings
Keyword(s):  
Angiotensin Ii ◽  
Respiratory Control ◽  
Circumventricular Organs ◽  
Strong Ion Difference ◽  
Concentration Difference ◽  
Peripheral Tissues ◽  
Central Chemoreceptors ◽  
Central Chemoreception ◽  
Increasing Temperature ◽  
The Brain

For optimal performance of exercising muscle, the charge state of proteins must be maintained; the pH environment of protein histidine imidazole groups must be coordinated with their pK. During exercise, increasing temperature and osmolality as well as changes in strong ions affect the pK of imidazole groups. Production of strong organic anions also decreases the concentration difference between strong cations and anions (strong ion difference, or [SID]), causing a metabolic acidosis in peripheral tissues. Central chemoreceptors regulate [Formula: see text] in relation to the [SID] of brain fluids to maintain a "constant" brain [H+]. In addition, increased osmolality, angiotensin II, and vasopressin during exercise may stimulate circumventricular organs of the brain and interact with chemical control of ventilation. Changes in [SID] of brain fluids during exercise are negligible compared to systemic decreases in [SID]; thus, regulation of [Formula: see text] to maintain brain [H+] homeostasis cannot simultaneously compensate for greater changes in [SID] in peripheral tissues. Key words: circumventricular organs, central chemoreception, angiotensin II, vasopressin, alphastat theory

Widespread sites of brain stem ventilatory chemoreceptors

1993 ◽  
Vol 75 (1) ◽  
pp. 5-14 ◽  
Author(s):  
E. L. Coates ◽  
A. Li ◽  
E. E. Nattie
Keyword(s):  
Brain Stem ◽  
Central Chemoreceptors ◽  
Maximum Value ◽  
Brain Ph ◽  
Chemosensitive Areas ◽  
Tissue Acidosis ◽  
Central Chemoreception ◽  
End Tidal ◽  
The Brain ◽  
Stimulation Of

We produced local tissue acidosis in various brain stem regions with 1-nl injections of acetazolamide (AZ) to locate the sites of central chemoreception. To determine whether the local acidosis resulted in a stimulation of breathing, we performed the experiment in chloralose-urethan anesthetized vagotomized carotid-denervated (cats) paralyzed servo-ventilated cats and rats and measured phrenic nerve activity (PNA) as the response index. Measurements of extracellular brain tissue pH by glass microelectrodes showed that AZ injections induced a change in pH at the injection center equivalent to that produced by an increase in end-tidal PCO2 of approximately 36 Torr and that the change in brain pH was limited to a tissue volume with a radius of < 350 microns. We found AZ injections sites that caused a significant increase in PNA to be located 1) within 800 microns of the ventrolateral medullary surface at locations within traditional rostral and caudal chemosensitive areas and the intermediate area, 2) within the vicinity of the nucleus tractus solitarii, and 3) within the vicinity of the locus coeruleus. Single AZ injections produced increases in PNA that were < or = 69% of the maximum value observed with an increase in end-tidal PCO2. We conclude that central chemoreceptors are distributed at many locations within the brain stem, all within 1.5 mm of the surface, and that stimulation of a small fraction of all central chemoreceptors can result in a large ventilatory response.

CO2 dialysis in the medullary raphe of the rat increases ventilation in sleep

2001 ◽  
Vol 90 (4) ◽  
pp. 1247-1257 ◽  
Author(s):  
Eugene E. Nattie ◽  
Aihua Li
Keyword(s):  
Eye Movement ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Arousal State ◽  
Retrotrapezoid Nucleus ◽  
Central Chemoreceptors ◽  
Artificial Cerebrospinal Fluid ◽  
Medullary Raphe ◽  
Tissue Acidosis ◽  
End Tidal

Central chemoreceptors are widespread within the brain stem. We hypothesize that function at different sites varies with arousal state. In unanesthetized rats, we produced focal acidification at single sites by means of microdialysis using artificial cerebrospinal fluid equilibrated with 25% CO2. Tissue acidosis, measured under anesthesia, is equivalent to that observed with 63 Torr end-tidal Pco 2 and is limited to 600 μm. Focal acidification of the retrotrapezoid nucleus increased ventilation by 24% only in wakefulness via an increase in tidal volume (Li A, Randall M, and Nattie E. J Appl Physiol 87: 910–919, 1999). In this study of the medullary raphe, the effect of such focal acidification was in sleep (defined by electroencephalographic and electromyographic criteria): ventilation and frequency increased by 15–20% in non-rapid eye movement sleep, and frequency increased by 15% in rapid eye movement sleep. There was no effect in wakefulness. Chemoreception in the medullary raphe appears to be responsive in sleep. Central chemoreceptors at two different locations appear to vary in effectiveness with arousal state.

Pontile regulation of ventilatory activity in the adult rat

1993 ◽  
Vol 74 (6) ◽  
pp. 2801-2811 ◽  
Author(s):  
W. Wang ◽  
M. L. Fung ◽  
W. M. St John
Keyword(s):  
Control System ◽  
Brain Stem ◽  
Mammalian Species ◽  
Respiratory Control ◽  
Ventilatory Control ◽  
Adult Rats ◽  
Adult Rat ◽  
Electrolytic Lesions ◽  
Pneumotaxic Center ◽  
The Brain

Our purpose was to characterize the pontile components of the brain stem ventilatory control system in rats. This study was precipitated by reports that this pontile component might differ fundamentally from that of other species. Efferent activity of the phrenic nerve was recorded in anesthetized, vagotomized, paralyzed, and ventilated adult rats. As in other species, electrical stimulations of the rostral pons caused premature terminations and/or onsets of phrenic activity in eupnea. Electrolytic lesions of rostrolateral pons resulted in apneusis, characterized by significant prolongations of the phrenic burst. Some effective lesions were in the region of the nucleus parabrachialis medialis and the Kolliker-Fuse nucleus, the site of the pneumotaxic center. Other lesions resulting in apneusis were ventral to the pneumotaxic center. As in cats, lesions in the caudal pontile reticular formation caused the duration of the apneustic neural inspiration to return toward that of eupnea. Again, as in other species, gradual alterations from eupnea to gasping in the rat were recorded during hypoxia, which was induced by ventilation with carbon monoxide. We conclude that the brain stem respiratory control system is similarly organized in rats and other mammalian species. These results have implications for contemporary hypotheses concerning the neurogenesis of ventilatory activity.

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