Developmental neuropathology of brainstem respiratory centers in unexplained stillbirth: What's the meaning?

During exposure to hypoxia newborns hypoventilate following a brief period of hyperventilation. Failure of integration of the afferent signals from peripheral O2 chemoreceptors due to immaturity of the central respiratory centers could explain this paradoxical respiratory response. To test this hypothesis we have utilized anesthetized, paralyzed, mechanically ventilated newborn piglets and lambs (less than 11 days) and old piglets (19–35 days). The vagus nerves were cut in each animal. Respiratory activity was quantified by integration of phrenic neural activity. A carotid sinus nerve (CSN) was isolated and electrically stimulated for periods of 1–6 min. In all three groups of animals respiratory activity was continuously elevated throughout the period of CSN stimulation. After CSN stimulation respiratory activity immediately declined about 25% from the stimulated value. Thereafter respiratory activity declined in an exponential fashion toward the initial control level of respiratory activity. The time constant of this latter decay was 84.2 s in the young piglets, 83.2 s in the old piglets, and 63.0 s in the lambs. These results indicate that the respiratory centers of newborn piglets and lambs can maintain integration of continuous afferent CSN activity. Further, the respiratory afterdischarge that follows CSN stimulus cessation is similar to that of adults. These studies indicate that, during periods of O2 sufficiency, the central respiratory centers of newborns respond in a qualitatively similar manner to CSN stimulation as do adult cats.

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LOCALIZATION OF THE MEDULLARY RESPIRATORY CENTERS IN THE CAT

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1939.126.3.673 ◽

1939 ◽

Vol 126 (3) ◽

pp. 673-688 ◽

Cited By ~ 127

Author(s):

R. F. Pitts ◽

H. W. Magoun ◽

S. W. Ranson

Keyword(s):

Respiratory Centers

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Basic Oscillating Mechanism of Cheyne-Stokes Breathing

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1956.187.2.395 ◽

1956 ◽

Vol 187 (2) ◽

pp. 395-398 ◽

Cited By ~ 126

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.

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Ventilatory response of intact cats to carbon monoxide hypoxia

Journal of Applied Physiology ◽

10.1152/jappl.1983.55.4.1064 ◽

1983 ◽

Vol 55 (4) ◽

pp. 1064-1071 ◽

Cited By ~ 17

Author(s):

H. Gautier ◽

M. Bonora

Keyword(s):

Carbon Monoxide ◽

Brain Stem ◽

Ventilatory Response ◽

Hypoxic Hypoxia ◽

Small Decrease ◽

Low Concentrations ◽

Initial Decrease ◽

Respiratory Centers ◽

Ventilatory Response To Co2

Adult intact conscious or anesthetized cats have been exposed to either hypoxia or low concentrations of CO in air. In addition, the ventilatory response to CO2 was studied in air, hypoxic hypoxia, and CO hypoxia. The results show that 1) in conscious cats, low concentrations of CO (0.15%) induce a slight decrease in ventilation and higher concentrations of CO (0.20%) induce first a small decrease in ventilation and then a characteristic tachypnea similar to the hypoxic tachypnea described in carotid-denervated cats; 2) in anesthetized cats, CO hypoxia induces only mild changes in ventilation; and 3) the ventilatory response to CO2 is increased in CO hypoxia in both conscious and anesthetized animals but differs from the increase observed during hypoxia. It is concluded that the initial decrease in ventilation may be caused by some brain stem depression of the respiratory centers with CO hypoxia, whereas the tachypnea originates probably at some suprapontine level. Conversely, the possible central acidosis may account for the potentiation of the ventilatory response to CO2 observed in either conscious or anesthetized animals.

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Sex-dependent regulation of hypoxic ventilation in mice and humans is mediated by erythropoietin

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.90967.2008 ◽

2009 ◽

Vol 296 (6) ◽

pp. R1837-R1846 ◽

Cited By ~ 34

Author(s):

Jorge Soliz ◽

Jonas Juhl Thomsen ◽

Christophe Soulage ◽

Carsten Lundby ◽

Max Gassmann

Keyword(s):

Ventilatory Response ◽

Hypoxic Exposure ◽

Hypoxic Ventilatory Response ◽

Sexual Hormones ◽

Female Mice ◽

Knowing That ◽

Human Volunteers ◽

Respiratory Centers ◽

The Brain ◽

Transgenic Male

Acclimatization to hypoxic exposure relies on an elevated ventilation and erythropoietic activity. We recently proposed that erythropoietin (Epo) links both responses: apart from red blood cell production, cerebral and plasma Epo interact with the central and peripheral respiratory centers. Knowing that women cope better than men with reduced oxygen supply (as observed at high altitude), we analyzed the hypoxic ventilatory response in Epo-overexpressing transgenic male and female mice with high Epo levels in brain and plasma (Tg6) or in wild-type animals injected with recombinant human Epo (rhEpo). Exposure to moderate and severe hypoxia as well as to hyperoxia and injection of domperidone, a potent peripheral ventilatory stimulant, revealed that the presence of transgenic or rhEpo extensively increased the hypoxic ventilatory response in female mice compared with their corresponding male siblings. Alterations of catecholamines in the brain stem's respiratory centers were also sex dependent. In a proof-of-concept study, human volunteers were intravenously injected with 5,000 units rhEpo and subsequently exposed to 10% oxygen. Compared with men, the hypoxic ventilatory response was significantly increased in women. We conclude that Epo exerts a sex-dependent impact on hypoxic ventilation improving the response in female mice and in women that most probably involves sexual hormones. Our data provides an explanation as to why women are less susceptible to hypoxia-associated syndromes than men.

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Periodic respiration of gill-breathing fishes

Canadian Journal of Zoology ◽

10.1139/z88-025 ◽

1988 ◽

Vol 66 (1) ◽

pp. 182-190 ◽

Cited By ~ 13

Author(s):

John L. Roberts ◽

David M. Rowell

Keyword(s):

Energy Savings ◽

Open Water ◽

Freshwater Species ◽

Jaw Muscles ◽

Reflex Pathways ◽

Periodic Respiration ◽

Gill Ventilation ◽

Respiratory Centers ◽

Ram Ventilation ◽

Respiratory Movements

Rhythmic and arrhythmic patterns of breathing are common among gill-breathing fishes. Irregular, short bouts of apnea occur in most fishes during feeding, while long apneic periods are routine for many open-water fishes such as scombrids, which ram ventilate during cruise swimming. During ram ventilation, the work of gill ventilation is transferred from the respiratory to the swimming musculature, with energy savings due to reductions in drag and inertial losses. Noncontinuous swimmers, such as some benthic and midwater marine and freshwater species, seldom cease rhythmic respiratory movements or resort to ram ventilation. When quiescent, they may adopt patterns of secondary cycling, alternating between respiratory pauses and short periods of rhythmic branchial pumping. Types and locations of chemo- and mechano-receptors that trigger changes in respiratory patterns of fish are being identified, as are the reflex pathways linking them to brainstem respiratory centers. A new mechanoreceptor is described that overlies the adductor mandibulae jaw muscles and may be of use in the modulation of cyclic respiratory movements. Respiratory switching control between rhythmic and ram gill ventilation is discussed.

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Experimental data on the mechanism of direct lesion of the medulla oblongata in acute diffuse peritonitis

Kazan medical journal ◽

10.17816/kazmj79875 ◽

1929 ◽

Vol 25 (7-8) ◽

pp. 776-786

Author(s):

P. V. Manenkov

Keyword(s):

Experimental Data ◽

Medulla Oblongata ◽

Diffuse Peritonitis ◽

Long Time ◽

Respiratory Centers

The question of the cause of the extremely severe course and death in acute diffuse peritonitis remained unresolved for a long time. The work of Heineke establishes that this reason lies in the paralysis of the vasomotor and respiratory centers of the medulla oblongata. However, this could not exhaust this issue.

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Postictal brainstem hypoperfusion and risk factors for sudden unexpected death in epilepsy

Neurology ◽

10.1212/wnl.0000000000010360 ◽

2020 ◽

Vol 95 (12) ◽

pp. e1694-e1705

Author(s):

Jonathan Liu ◽

Joseph S. Peedicail ◽

Ismael Gaxiola-Valdez ◽

Emmy Li ◽

Victoria Mosher ◽

...

Keyword(s):

Arterial Spin Labeling ◽

Spin Labeling ◽

Regions Of Interest ◽

Sudden Unexpected Death ◽

Seizure Type ◽

Unexpected Death ◽

Increased Risk ◽

Impaired Awareness ◽

Clonic Seizures ◽

Respiratory Centers

ObjectiveSince the strongest risk factor for sudden unexpected death in epilepsy (SUDEP) is frequent bilateral tonic-clonic seizures (BTCS), our aim was to determine whether postictal hypoperfusion in brainstem respiratory centers (BRCs) is more common following tonic-clonic seizures.MethodsWe studied 21 patients with focal epilepsies who underwent perfusion imaging with arterial spin labeling MRI. Subtraction maps of cerebral blood flow were obtained from the postictal and baseline scans. We identified 6 regions of interest in the brainstem that contain key BRCs. Patients were considered to have postictal BRC hypoperfusion if any of the 6 regions of interest were significantly hypoperfused.ResultsAll 6 patients who experienced BTCS during the study had significant clusters of postictal hypoperfusion in BRCs compared to 7 who had focal impaired awareness seizures (7/15). The association between seizure type studied and the presence of BRC hypoperfusion was significant. Duration of epilepsy and frequency of BTCS were not associated with postictal brainstem hypoperfusion despite also being associated with risk for SUDEP.ConclusionPostictal hypoperfusion in brainstem respiratory centers occurs more often following BTCS than other seizure types, providing a possible explanation for the increased risk of SUDEP in patients who regularly experience BTCS.

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