Predominant role of peripheral chemoreceptors in the termination of apnea in maturing newborn lambs

Apneas are very common and normal in newborns but may become life threatening if they are not terminated appropriately. The aim of this study in newborn lambs was to investigate the influence on apnea termination of postnatal maturation, peripheral chemoreceptor function, and hypoxia. Apneas were induced by passive hyperventilation at varying inspired O2 fraction levels. The apnea termination threshold PCO2 (PATTCO2) was defined as the arterial PCO2 value at the first breath after the apnea. Three groups of awake intubated lambs were studied: 1) intact lambs tested at both 1 and 15 days of life, 2) intact 1-day-old lambs with central tissue hypoxia induced by CO inhalation, and 3) 1-day-old lambs with carotid body denervation (CBD). In individual lambs and regardless of age and carotid body function, there was a PO2-PCO2 response curve that was a determinant for the termination of an apnea. PATTCO2 invariably increased when arterial PO2 increased, regardless of age. During hypoxia and normoxia, PATTCO2 was significantly lower in 15-day-old lambs compared with 1-day-old lambs. No difference was seen during hyperoxia. PATTCO2 values were shifted to higher levels after carotid body removal. Finally, hypoxia induced by either a low inspired O2 fraction or CO inhalation consistently failed to induce a depressive effect on the PATTCO2 even in CBD lambs. In conclusion, in awake newborn lambs, the PCO2 level for apnea termination changed with postnatal age, and carotid body function was essential in lowering PATTCO2, thus protecting the lambs against prolonged apnea. Furthermore, hypoxia consistently failed to depress the reinitiation of breathing after apnea, even in CBD lambs.

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Carotid chemoreceptor activity during acute and sustained hypoxia in goats

Journal of Applied Physiology ◽

10.1152/jappl.1988.65.4.1796 ◽

1988 ◽

Vol 65 (4) ◽

pp. 1796-1802 ◽

Cited By ~ 87

Author(s):

A. M. Nielsen ◽

G. E. Bisgard ◽

E. H. Vidruk

Keyword(s):

Carotid Body ◽

Discharge Frequency ◽

Hypoxic Exposure ◽

Arterial Pco2 ◽

Afferent Discharge ◽

Carotid Body Chemoreceptors ◽

Arterial Po2 ◽

Sustained Hypoxia ◽

Related Increase

The role of carotid body chemoreceptors in ventilatory acclimatization to hypoxia, i.e., the progressive, time-dependent increase in ventilation during the first several hours or days of hypoxic exposure, is not well understood. The purpose of this investigation was to characterize the effects of acute and prolonged (up to 4 h) hypoxia on carotid body chemoreceptor discharge frequency in anesthetized goats. The goat was chosen for study because of its well-documented and rapid acclimatization to hypoxia. The response of the goat carotid body to acute progressive isocapnic hypoxia was similar to other species, i.e., a hyperbolic increase in discharge as arterial PO2 (PaO2) decreased. The response of 35 single chemoreceptor fibers to an isocapnic [arterial PCO2 (PaCO2) 38-40 Torr)] decrease in PaO2 of from 100 +/- 1.7 to 40.7 +/- 0.5 (SE) Torr was an increase in mean discharge frequency from 1.7 +/- 0.2 to 5.8 +/- 0.4 impulses. During sustained isocapnic steady-state hypoxia (PaO2 39.8 +/- 0.5 Torr, PaCO2, 38.4 +/- 0.4 Torr) chemoreceptor afferent discharge frequency remained constant for the first hour of hypoxic exposure. Thereafter, single-fiber chemoreceptor afferents exhibited a progressive, time-related increase in discharge (1.3 +/- 0.2 impulses.s-1.h-1, P less than 0.01) during sustained hypoxia of up to 4-h duration. These data suggest that increased carotid chemoreceptor activity contributes to ventilatory acclimatization to hypoxia.

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Postnatal maturation of respiration in intact and carotid body-chemodenervated lambs

Journal of Applied Physiology ◽

10.1152/jappl.1985.59.3.869 ◽

1985 ◽

Vol 59 (3) ◽

pp. 869-874 ◽

Cited By ~ 50

Author(s):

M. A. Bureau ◽

J. Lamarche ◽

P. Foulon ◽

D. Dalle

Keyword(s):

Tidal Volume ◽

Respiratory Rate ◽

Carotid Body ◽

Minute Ventilation ◽

Inspiratory Flow ◽

Occlusion Pressure ◽

Inspiratory Time ◽

Arterial Pco2 ◽

Postnatal Maturation ◽

Arterial Po2

The contribution of the carotid body chemoreceptor to postnatal maturation of breathing was evaluated in lambs from 7 to 70 days of age. The study was conducted by comparing the eupneic ventilation and resting pneumograms in intact conscious lambs with those of lambs that were carotid body chemodenervated (CBD) at birth. In comparison to the 1-wk-old intact lambs, the CBD lambs had significant decreases in minute ventilation (VE, 313 vs. 517 ml/kg), tidal volume (VT, 7.2 vs. 10.5 ml/kg), respiratory rate (f, 44 vs. 51 breaths/min), and occlusion pressure (P0.1, 2.8 vs. 7.2 cmH2O). Arterial PO2's were 59 vs. 75 Torr (P less than 0.05) and arterial PCO2's 47 vs. 36 Torr (P less than 0.05), respectively, in CBD and intact lambs. In intact lambs from 7 to 70 days, resting VE decreased progressively from 517 to 274 ml/kg (P less than 0.01) due to a fall in VT, mean inspiratory flow (VT/TI), and f, whereas the ratio of inspiratory time to total breath duration remained constant. P0.1 decreased from 7.2 to 3.9 cmH2O from 7 to 42 days. In contrast the CBD lambs experienced only minimal changes in VE, VT, VT/TI, and f during the same period. VE only decreased from 313 to 218 and P0.1 from 2.8 to 2.4 cmH2O. In contrast to that of intact lambs the resting pneumogram of CBD lambs remained relatively fixed from 7 to 70 days. Three CBD lambs died unexpectedly, without apparent cause, in the 4th and 5th wk of life.

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Role of Cl--HCO3 - Exchanger and Anion Channel in the Cat Carotid Body Function

Control of Breathing and Its Modeling Perspective ◽

10.1007/978-1-4757-9847-0_20 ◽

1992 ◽

pp. 119-122 ◽

Cited By ~ 1

Author(s):

Rodrigo Iturriaga ◽

Sukhamay Lahiri

Keyword(s):

Carotid Body ◽

Anion Channel ◽

Body Function

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Role of nicotinic receptors on carotid body function in developing rats.

The FASEB Journal ◽

10.1096/fasebj.23.1_supplement.961.5 ◽

2009 ◽

Vol 23 (S1) ◽

Author(s):

Lalah Niane ◽

Vincent Joseph ◽

Aida Bairam

Keyword(s):

Carotid Body ◽

Nicotinic Receptors ◽

Body Function

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Postnatal maturation of peripheral chemoreceptor ventilatory response to O2 and CO2 in newborn lambs

Journal of Applied Physiology ◽

10.1152/jappl.1996.80.6.1928 ◽

1996 ◽

Vol 80 (6) ◽

pp. 1928-1933 ◽

Cited By ~ 11

Author(s):

E. Canet ◽

I. Kianicka ◽

J. P. Praud

Keyword(s):

Carotid Body ◽

Ventilatory Response ◽

Time Frame ◽

Peripheral Chemoreceptor ◽

Postnatal Maturation ◽

Time Courses ◽

End Tidal ◽

Peripheral Chemoreflex ◽

End Tidal Co2

Although studies on lambs have shown that carotid body sensitivity to O2 is reset postnatally, it is still unknown whether O2 and CO2 peripheral chemoreflexes undergo parallel postnatal maturation. The present study was designed to analyze maturation of O2 and CO2 peripheral chemoreflexes in 10 lambs at < 24 h and at 12 days of age. We measured the ventilatory (VE) response to three tidal breaths of pure N2 or 13% CO2 in air. Overall, the N2 peripheral chemoreflex increased significantly with maturation [VE/end-tidal O2 (ml.min-1.kg-1.Torr-1) = 2.94 +/- 0.91 at < 24 h vs. 5.13 +/- 0.59 at 12 days, P < 0.05], whereas the CO2 peripheral chemoreflex did not change (VE/end-tidal CO2 = 7.04 +/- 0.98 at < 24 h vs. 7.75 +/- 1.07 at 12 days, not significant). We conclude that the CO2 peripheral chemoreflex does not change in awake lambs within the time frame studied, in contrast to a marked postnatal maturation of the O2 peripheral chemoreflex. The different time courses of O2 and CO2 peripheral chemoreflex maturation support the concept that carotid body sensitivities to O2 and CO2 do not depend on the same basic mechanisms.

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Hypoglycemia selectively abolishes hypoxic reactivity of pial arterioles in piglets: role of adenosine

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1995.268.2.h871 ◽

1995 ◽

Vol 268 (2) ◽

pp. H871-H878 ◽

Cited By ~ 1

Author(s):

T. S. Park ◽

E. R. Gonzales ◽

A. R. Shah ◽

J. M. Gidday

Keyword(s):

Arterial Pco2 ◽

Adenosine Receptor Antagonist ◽

Cranial Window ◽

Newborn Piglets ◽

Window Technique ◽

Pial Arterioles ◽

Cerebrovascular Regulation ◽

Arterial Po2 ◽

Arteriolar Diameter

Episodes of hypoxia often occur in hypoglycemic newborns, but it is not known whether dysfunctions in cerebrovascular regulation contribute to brain injury incurred by these affected neonates. We tested the hypotheses that 1) perinatal hypoglycemia impairs cerebrovascular responses to hypoxia and 2) a reduced vascular smooth muscle sensitivity to adenosine accounts for this impairment. Responses of 25- to 50-mu m-diam pial arterioles were determined using the cranial window technique in isoflurane-anesthetized newborn piglets < 5 days of age. Hypoxia (arterial PO2 = 28 +/- 1 mmHg) caused a 47 +/- 5% increase (P = 0.0008) in arteriolar diameter, 89% of which could be blocked by prior superfusion of the window space with the preferential A2-adenosine receptor antagonist 3,7-dimethyl-1-propargylxanthine (DMPX; 50 microM). Insulin-induced hypoglycemia (blood glucose = 18 +/- 1 mg/dl without isoelectric electroencephalogram) caused a 31 +/- 5% increase (P = 0.002) in arteriolar diameter; however, no additional dilatative response to hypoxia (arterial PO2 = 28 +/- 1 mmHg) could be elicited in these animals. Arteriolar dilation of 41 +/- 6% (P = 0.002) induced by superfusion of 20 microM adenosine under normoglycemic conditions was also completely abolished after the animals were rendered hypoglycemic. Unlike the response to hypoxia and adenosine, hypoglycemia only attenuated prostanoid-dependent dilations to hypercapnia (arterial PCO2 = 68 +/- 3 mmHg) by 55 +/- 9%. These results indicate that, in the newborn, hypoglycemia selectively abolishes hypoxic reactivity through an impairment in adenosine-mediated cerebrovascular dilation.

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Role of beta adrenergic receptors in carotid body function of the goat

Respiration Physiology ◽

10.1016/0034-5687(86)90042-3 ◽

1986 ◽

Vol 64 (2) ◽

pp. 203-211 ◽

Cited By ~ 6

Author(s):

David W. Hudgel ◽

Nancy A. Kressin ◽

Ann M. Nielsen ◽

Gerald E. Bisgard

Keyword(s):

Carotid Body ◽

Adrenergic Receptors ◽

Beta Adrenergic Receptors ◽

Beta Adrenergic ◽

Body Function

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Postnatal maturation of carotid chemoreceptor responses to O2 and CO2 in the cat

Journal of Applied Physiology ◽

10.1152/jappl.1993.75.6.2383 ◽

1993 ◽

Vol 75 (6) ◽

pp. 2383-2391 ◽

Cited By ~ 69

Author(s):

J. L. Carroll ◽

O. S. Bamford ◽

R. S. Fitzgerald

Keyword(s):

Time Course ◽

Carotid Sinus ◽

Neonatal Period ◽

Moving Average ◽

Neural Responses ◽

Arterial Pco2 ◽

Postnatal Maturation ◽

Steady Level ◽

Adult Cats ◽

Arterial Po2

This study aimed to characterize neural responses of the carotid chemoreceptors of the maturing cat to natural stimuli and to determine the time course of carotid chemoreceptor development from the neonatal period to adulthood. Carotid sinus nerve (CNS) responses to O2 and CO2 were studied in cats at 1, 4, and 8 wk of age and in adult cats (n = 6 at each age). Pentobarbital sodium-anesthetized cats were exposed to three levels of O2 (arterial PO2 = 40–45, 80–90, and > 300 Torr) at five levels of arterial PCO2 (22, 35, 48, 63, and 75 Torr) while the moving average of whole nerve output from the CSN was recorded. Ganglioglomerular nerves were sectioned. All cats at every age increased CSN activity during hypoxia. However, the CSN response to hypoxia was not sustained in some immature cats. Of the cats that sustained CSN activity during hypoxia, four of the six 1-wk-old cats showed a biphasic pattern of response, with an initial overshoot followed by a steady level of discharge. Older cats did not exhibit this pattern. CNS sensitivity to hypoxia was weakest in 1-wk-old kittens but increased to nearly adult levels by 4 wk of age. Carotid chemoreceptor responses to CO2 were also smallest in 1-wk-old kittens and increased with maturation. However, unlike hypoxia responses, CO2 sensitivity during hypoxia continued to develop between 8 wk and adulthood. O2-CO2 interaction did not become significant until after 4 wk of age. Thus, carotid chemoreceptor responses to both O2 and CO2 are weak in newborn cats and increase during postnatal development.(ABSTRACT TRUNCATED AT 250 WORDS)

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A Possible Role of the Carotid Body in the Pathogenesis of Cluster Headache

Cephalalgia ◽

10.1046/j.1468-2982.1983.0304241.x ◽

1983 ◽

Vol 3 (4) ◽

pp. 241-247 ◽

Cited By ~ 17

Author(s):

Lee Kudrow

Keyword(s):

Cluster Headache ◽

Carotid Body ◽

Cranial Nerves ◽

Major Influence ◽

Peripheral Chemoreceptor ◽

Afferent Pathways ◽

The Third ◽

Cyclic Cluster ◽

Stimulation Of

An hypothesis regarding the possible role of the carotid body in the pathogenesis of cluster headache is presented. It states: 1. The pathways concerned with cyclic cluster periods may begin centrally involving specific areas in the hypothalamus. The major influence of this physiological change is proposed to be an inhibition of the sympathetic and disinhibition of parasympathetic supplies to the carotid body. The result, whether due to increased vasomotor tonus or interruption of intrinsic sympathetic stimulation, is suggested to cause diminished peripheral chemoreceptor activity. 2. The pathway concerned with onset of spontaneous or induced attacks begins, as proposed, with oxygen desaturation-which, upon reaching threshold levels may induce a hyperactive chemoreceptor response, and stimulate through afferent pathways the nuclei of the 7th and 10th cranial nerves and respiratory centers, via the nucleus solitarius. 3. The consequence of this excitation may involve the third suggested pathway resulting in stimulation of peripheral secretory and other receptors innervated by the cranial nerves.

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