Hypoxic Modulation of Central Chemosensitivity

Role of peripheral chemoreceptors and central chemosensitivity in the regulation of respiration and circulation.

Journal of Experimental Biology ◽

10.1242/jeb.100.1.23 ◽

1982 ◽

Vol 100 (1) ◽

pp. 23-40 ◽

Cited By ~ 1

Author(s):

R G O'Regan ◽

S Majcherczyk

Keyword(s):

The Body ◽

Ion Concentration ◽

Regulation Of Respiration ◽

Acid Base Balance ◽

Acid Base ◽

Vascular Effects ◽

Peripheral Chemoreceptor ◽

Hydrogen Ion Concentration ◽

Central Chemosensitivity ◽

Base Balance

Adjustments of respiration and circulation in response to alterations in the levels of oxygen, carbon dioxide and hydrogen ions in the body fluids are mediated by two distinct chemoreceptive elements, situated peripherally and centrally. The peripheral arterial chemoreceptors, located in the carotid and aortic bodies, are supplied with sensory fibres coursing in the sinus and aortic nerves, and also receive sympathetic and parasympathetic motor innervations. The carotid receptors, and some aortic receptors, are essential for the immediate ventilatory and arterial pressure increases during acute hypoxic hypoxaemia, and also make an important contribution to respiratory compensation for acute disturbances of acid-base balance. The vascular effects of peripheral chemoreceptor stimulation include coronary vasodilation and vasoconstriction in skeletal muscle and the splanchnic area. The bradycardia and peripheral vasoconstriction during carotid chemoreceptor stimulation can be lessened or reversed by effects arising from a concurrent hyperpnoea. Central chemoreceptive elements respond to changes in the hydrogen ion concentration in the interstitial fluid in the brain, and are chiefly responsible for ventilatory and circulatory adjustments during hypercapnia and chronic disturbances of acid-base balance. The proposal that the neurones responsible for central chemoreception are located superficially in the ventrolateral portion of the medulla oblongata is not universally accepted, mainly because of a lack of convincing morphological and electrophysiological evidence. Central chemosensitive structures can modify peripheral chemoreceptor responses by altering discharges in parasympathetic and sympathetic nerves supplying these receptors, and such modifications could be a factor contributing to ventilatory unresponsiveness in mild hypoxia. Conversely, peripheral chemoreceptor drive can modulate central chemosensitivity during hypercapnia.

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Site of central chemosensitivity in fetal sheep

Journal of Applied Physiology ◽

10.1152/jappl.1975.39.1.1 ◽

1975 ◽

Vol 39 (1) ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

A. H. Jansen ◽

V. Chernick

Keyword(s):

Blood Pressure ◽

Spinal Cord ◽

Heart Rate ◽

Respiratory Response ◽

Fetal Sheep ◽

Central Chemosensitivity ◽

Cord Clamping ◽

Chemosensitive Areas ◽

Ventral Medullary Surface ◽

Histotoxic Hypoxia

The heart rate, blood pressure, and respiratory response to topically applied cyanide on the ventrolateral medullary surface and upper spinal cord was studied on exteriorized sinaortic-denervated fetal lambs under pentobarbital anesthesia. On all sites tested cyanide produced a rapid increase in heart rate and blood pressure (P smaller than 0.05) which was most pronounced from the area adjacent to the nerve roots IX to XI (mean 32%). Respiratory efforts consisting of 1–8 gasps were induced in half the applications to the medulla but never when the pledgets were applied to the spinal cord. The mean delay to response was 43 s (range 13–102 s). After cautery of the chemosensitive areas, topical application of cyanide failed to stimulate gasping, whereas intravenous cyanide or cord clamping still produced a vigorous respiratory response. It is concluded that sympathetic stimulation of the heart and blood vessels can originate centrally in response to local histotoxic hypoxia of the ventral medulla and upper spinal cord. Furthermore, it is proposed that in the apneic fetus histotoxic hypoxia of the medulla initiates respiration possibly by stimulating a special gasping mechanism which is separate from the respiratory center responsible for rhythmic breathing after birth. The responsible neurons must be located at least 2 mm beneath the ventral medullary surface.

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Vagal input enhances responsiveness of respiratory discharge to central changes in pH/CO2 in bullfrogs

Journal of Applied Physiology ◽

10.1152/jappl.1994.77.4.2048 ◽

1994 ◽

Vol 77 (4) ◽

pp. 2048-2051 ◽

Cited By ~ 41

Author(s):

R. Kinkead ◽

W. G. Filmyer ◽

G. S. Mitchell ◽

W. K. Milsom

Keyword(s):

Breathing Pattern ◽

Intrinsic Property ◽

Afferent Input ◽

Motor Output ◽

Burst Frequency ◽

Central Chemosensitivity ◽

Temporal Relationships ◽

The Central Nervous System ◽

Motor Nerves

This study investigated the interaction between vagal afferent input and central chemosensitivity in modulating the respiratory motor output of in vitro brain stem-spinal cord preparations from adult bullfrogs. With this preparation, the spatiotemporal distribution of respiratory-related motor output emulated that of intact bullfrogs; that is, the fictive breathing pattern was mostly episodic. Recordings from cranial motor nerves (V and X) showed that, without peripheral feedback, increasing the PCO2 of the mock cerebrospinal fluid (thereby reducing pH from 8.3 to 7.7) caused a modest increase in respiration-related burst frequency. When the pulmonary branch of a vagus nerve was stimulated phasically (2 V, 20 Hz, 0.2 ms) during each fictive breath to simulate afferent pulmonary stretch receptor feedback 1) the responsiveness of the preparation to the same changes in pH was augmented nearly threefold and 2) the breathing pattern remained episodic. It appears, therefore, that episodic breathing is an intrinsic property of the central nervous system in bullfrogs. It is concluded that there is a strong interaction between vagal feedback and central chemodetection in controlling the temporal relationships that characterize this episodic breathing pattern.

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Elevated exercise ventilation in mild COPD is not linked to enhanced central chemosensitivity

Respiratory Physiology & Neurobiology ◽

10.1016/j.resp.2020.103571 ◽

2021 ◽

Vol 284 ◽

pp. 103571

Author(s):

Devin B Phillips ◽

Nicolle J Domnik ◽

Amany F Elbehairy ◽

Megan E Preston ◽

Kathryn M Milne ◽

...

Keyword(s):

Central Chemosensitivity ◽

Exercise Ventilation

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Evidence for central chemoreception in the midline raphe

Journal of Applied Physiology ◽

10.1152/jappl.1996.80.1.108 ◽

1996 ◽

Vol 80 (1) ◽

pp. 108-115 ◽

Cited By ~ 129

Author(s):

D. G. Bernard ◽

A. Li ◽

E. E. Nattie

Keyword(s):

Cerebrospinal Fluid ◽

Brain Stem ◽

Focal Region ◽

Central Chemosensitivity ◽

Tissue Acidosis ◽

Central Chemoreception ◽

Injection Location

We injected acetazolamide (AZ; 5 x 10(-6) M; 1 nl; n = 14), its inactive analogue 2-acetylamino-1,3,4-thiadiazole-5-sulfon-t-butylamide (5 x 10(-5) M; n = 6), or mock cerebrospinal fluid (n = 5) into the caudal raphe in the midline brain stem of anesthetized paralyzed ventilated rats. These AZ injections have been shown to produce a focal region of tissue acidosis with a radius < 350 microns and are used as a probe for sites of central chemosensitivity. Compared with control injections, AZ injection into the raphe, as demonstrated by anatomic analysis of injection location, significantly increased the amplitude of the integrated phrenic neurogram over 10-40 min. Not all raphe injections produced such a response. AZ injections identified as responders (n = 8 of 14) increased integrated phrenic amplitude 43.3 +/- 10.7% (SE) of baseline 20 min after the injection. We conclude that the midline caudal raphe contains sites of ventilatory chemoreception.

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