Arterial blood gases in conscious rats exposed to hypoxia, hypercapnia, or both

Pepelko, William E.; Dixon, Gene A.

doi:10.1152/jappl.1975.38.4.581

Cited by 66 publications

(17 citation statements)

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“…After surgery the halothane level was set to 0.8%. The ventilation parameters were adjusted to maintain normocapnic arterial CO 2 levels (Pepelko and Dixon, 1975). No statistically significant difference in the pre-and postacquisition p a CO 2 values between groups was found (oneway analysis of variance, ANOVA, dof ¼ 14, F(2,13) ¼ 0.86; p ¼ 0.45).…”

Section: Phmrimentioning

confidence: 99%

Modulation of Fronto-Cortical Activity by Modafinil: A Functional Imaging and Fos Study in the Rat

Gozzi

Colavito

Etet

et al. 2011

Neuropsychopharmacol

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Modafinil (MOD) is a wake-promoting drug with pro-cognitive properties. Despite its increasing use, the neuronal substrates of MOD action remain elusive. In particular, animal studies have highlighted a putative role of diencephalic areas as primary neuronal substrate of MOD action, with inconsistent evidence of recruitment of fronto-cortical areas despite the established pro-cognitive effects of the drug. Moreover, most animal studies have employed doses of MOD of limited clinical relevance. We used pharmacological magnetic resonance imaging (phMRI) in the anesthetized rat to map the circuitry activated by a MOD dose producing clinically relevant plasma exposure, as here ascertained by pharmacokinetic measurements. We observed prominent and sustained activation of the prefrontal and cingulate cortex, together with weaker but significant activation of the somatosensory cortex, medial thalamic domains, hippocampus, ventral striatum and dorsal raphe. Correlation analysis of phMRI data highlighted enhanced connectivity within a neural network including dopamine projections from the ventral tegmental area to the nucleus accumbens. The pro-arousing effect of MOD was assessed using electroencephalographic recording under anesthetic conditions comparable to those used for phMRI, together with the corresponding Fos immunoreactivity distribution. MOD produced electroencephalogram desynchronization, resulting in reduced delta and increased theta frequency bands, and a pattern of Fos induction largely consistent with the phMRI study. Altogether, these findings show that clinically relevant MOD doses can robustly activate fronto-cortical areas involved in higher cognitive functions and a network of pro-arousing areas, which provide a plausible substrate for the wake-promoting and pro-cognitive effects of the drug.

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Section: Phmrimentioning

confidence: 99%

Modulation of Fronto-Cortical Activity by Modafinil: A Functional Imaging and Fos Study in the Rat

Gozzi

Colavito

Etet

et al. 2011

Neuropsychopharmacol

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“…In the caudal NTS, more labeled cells appeared after inhalation of 15% CO 2 than after exposure to 9% O 2 . In conscious rats, the latter challenge leads to a hypocapnic arterial PCO 2 of about 3 Kpa (Pepelko and Dixon, 1975;Kregel, 1996), which may have resulted in a lower carotid body activity than during the exposure to 15% CO 2 , thus explaining the smaller number of labeled cells in the caudal NTS.…”

Section: Dorsal Medullamentioning

confidence: 99%

“…Alternatively, the lack of Fos-positive neurons in the juxtafacial PGCl (and their smaller number in the retrofacial part) during hypoxia could be related to its function in arousal and alertness functions (Van Bockstaele and AstonJones, 1995). In awake rats, exposure to 10% O 2 results in a PaO 2 of approximately 30 mm Hg (Pepelko and Dixon, 1975;Kregel, 1996), and this may cause a decrease in their level of arousal. We could not observe behavioral differences in this respect between hypercapnic and hypoxic animals, because in both groups drowsiness was a regular observation (the animals were studied in their light period).…”

Section: Ventral Medullamentioning

confidence: 99%

Expression of c‐fos in the rat brainstem after exposure to hypoxia and to normoxic and hyperoxic hypercapnia

et al. 1997

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In this study, Fos immunohistochemistry was used to map brainstem neuronal pathways activated during hypercapnia and hypoxia. Conscious rats were exposed to six different gas mixtures: (a) air; (b) 8% CO2 in air; (c) 10% CO2 in air; (d) 15% CO2 in air; (e) 15% CO2 + 60% O2, balance N2; (f) 9% O2, balance N2. Double-staining was performed to show the presence of tyrosine hydroxylase. Hypercapnia, in a dose-dependent way caused Fos expression in the following areas: caudal nucleus tractus solitarius (NTS), with few labeled A2 noradrenergic neurons; noradrenergic A1 cells and noncatecholaminergic neurons in the caudal ventrolateral medulla; raphe magnus and gigantocellular nucleus pars alpha (GiA); many noncatecholaminergic (and relatively few C1) neurons in the lateral paragigantocellular nucleus (PGCl), and in the retrotrapezoid nucleus (RTN); locus coeruleus (LC), external lateral parabrachial and Kölliker-Fuse nuclei, and A5 noradrenergic neurons at pontine level; and in caudal mesencephalon, the ventrolateral column of the periaqueductal gray (vlPAG). In most of these nuclei, hypoxia also induced Fos expression, albeit generally less than after hypercapnia. However, hypoxia did not cause labeling in RTN, juxtafacial PGCl, GiA, LC, or vlPAG. After normoxic hypercapnia, more labeled cells were present in NTS and PGCl than after hyperoxic hypercapnia. Part of the observed labeling could be caused by stress- or cardiovascular-related sequelae of hypoxia and hypercapnia. Possible implications for the neural control of breathing are also discussed, particularly with regard to the finding that several nuclei, not belonging to the classical brainstem respiratory centres, contained labeled cells.

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“…Hypercapnic (8% CO 2 , 21% O 2 , and 71% N 2 ) and hypoxic (10% O 2 , 3% CO 2 , and 87% N 2 ) mixtures were introduced into the measurement chamber through a catheter (5-mL dead space). The hypoxic mixture contained 3% CO 2 to approach isocapnia during hypoxic stimulus (19).…”

Section: Ventilatory Measurementsmentioning

confidence: 99%

Impaired Ventilatory Responses to Hypoxia in Mice Deficient in Endothelin-Converting-Enzyme-1

et al. 2001

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Endothelin-converting-enzyme (ECE-1) catalyzes the proteolytic activation of big endothelin-1 to mature endothelin-1. Most homozygous ECE-1Ϫ/Ϫ embryos die in utero and show severe craniofacial, enteric, and cardiac malformations precluding ventilatory function assessment. In contrast, heterozygous ECE-1ϩ/Ϫ embryos develop normally. Their respiratory function at birth has not been studied. Taking into account previous respiratory investigations in mice with endothelin-1 gene disruption, we hypothesized that ECE-1-deficient mice may have impaired ventilatory control. We analyzed ventilatory responses to hypercapnia (8% CO 2 ) and hypoxia (10% O 2 ) in newborn and adult mice heterozygous for ECE-1 deficiency (ECE-1ϩ/Ϫ) and in their wild-type littermates (ECE-1ϩ/ϩ). Ventilation, breath duration, and tidal volume were measured using whole-body plethysmography. Ventilatory responses to hypoxia were significantly weaker in ECE-1ϩ/Ϫ than in ECE-1ϩ/ϩ newborn mice (percentage ventilation increase: 1 Ϯ 25% versus 33 Ϯ 29%, p ϭ 0.010). Baseline breathing variables and ventilatory responses to hypercapnia were normal in the ECE-1ϩ/Ϫ newborn mice. No differences were observed between adult ECE-1ϩ/Ϫ and ECE-1ϩ/ϩ mice. We conclude that ECE-1 is required for normal ventilatory response to hypoxia at birth. Abbreviations CCHS, congenital central hypoventilation syndrome ECE-1, endothelin-converting-enzyme-1 ET-1, endothelin-1 GDNF, glial-cell-line-derived neurotrophic factor HSCR, Hirschsprung's disease NTS, nucleus tractus solitarius RET, rearranged during transfection TTOT, breath duration VE, ventilation VT, tidal volume ECE-1 catalyzes the proteolytic activation of big ET-1 to mature ET-1 (1, 2). Targeted ECE-1 gene disruption, which has recently been achieved in mice, has important effects on embryonic development and autonomic functions (3). Among homozygous ECE-1Ϫ/Ϫ embryos, most die in utero (about 75% in a C57BL/6 -129SvEv hybrid background) and all exhibit craniofacial, enteric, and cardiac malformations (3) that preclude valid ventilatory function assessment. In contrast, heterozygous ECE-1ϩ/Ϫ newborns are apparently healthy and develop normally. In a recent study, the differences in respiratory function between adult heterozygous ECE-1ϩ/Ϫ and wild-type ECE-1ϩ/ϩ adult mice were found to be not significant (4). Newborn mice were not studied. In the present study, we tested the ventilatory responses to chemical stimuli in heterozygous ECE-1ϩ/Ϫ newborn mice, and we reexamined the normality of adult heterozygous ECE-1ϩ/Ϫ mice in a larger sample of mice than previously done (4).Our working hypothesis was based on previous data showing that ET-1 is required for normal ventilatory control. First, in anesthetized rats, topical applications of ET-1 in the chemosensitive area of the ventral medulla oblongata and other areas involved in respiratory control cause changes in phrenic nerve activity (2). Specifically, applications of ET-1 in regions extending between the caudal end of the trapezoid body and the rootlets of the XIIth ...

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Arterial blood gases in conscious rats exposed to hypoxia, hypercapnia, or both

Cited by 66 publications

References 0 publications

Modulation of Fronto-Cortical Activity by Modafinil: A Functional Imaging and Fos Study in the Rat

Modulation of Fronto-Cortical Activity by Modafinil: A Functional Imaging and Fos Study in the Rat

Expression of c‐fos in the rat brainstem after exposure to hypoxia and to normoxic and hyperoxic hypercapnia

Impaired Ventilatory Responses to Hypoxia in Mice Deficient in Endothelin-Converting-Enzyme-1

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