Repeated Apneas and Hypercapnic Ventilatory Response Before and After Apnea Training

2015 ◽  
Vol 86 (1) ◽  
pp. 27-33
Author(s):  
Dimitrios I. Bourdas ◽  
Theodoros S. Tsakiris ◽  
Konstantinos I. Pavlakis ◽  
Despoina V. Triantafillou ◽  
Nickos D. Geladas
Keyword(s):  
Ventilatory Response ◽  
Hypercapnic Ventilatory Response ◽  
Before And After

Conditional depletion of methyl-CpG-binding protein 2 in astrocytes depresses the hypercapnic ventilatory response in mice

2015 ◽  
Vol 119 (6) ◽  
pp. 670-676 ◽  
Author(s):  
Saurabh K. Garg ◽  
Daniel T. Lioy ◽  
Sharon J. Knopp ◽  
John M. Bissonnette
Keyword(s):  
Transcription Factor ◽  
Ventilatory Response ◽  
Binding Protein ◽  
Minute Ventilation ◽  
Cre Recombinase ◽  
Relative Increase ◽  
Mecp2 Gene ◽  
Hypercapnic Ventilatory Response ◽  
Selective Depletion ◽  
Before And After

Mice that are deficient in the transcription factor methyl-CpG-binding protein 2 (MeCP2) have a depressed hypercapnic ventilatory response (HCVR). The expression of MeCP2 can be selectively removed from astrocytes or neurons, thus offering a tool to dissect the role of this transcription factor in astrocytes from that in neurons. Studies were carried out in the progeny of mice that were a cross between those harboring a tamoxifen (TAM)-inducible Cre recombinase transgene driven by the human astrocytic glial fibrillary acidic protein (hGFAP) promoter, or Cre recombinase under control of the synapsin promoter, with mice containing a Cre-excisable exon III in the Mecp2 gene. The TAM-conditional excision of the Mecp2 exon allowed the respiratory CO2 response to be studied in the same animals before and after selective depletion of MeCP2 in astrocytes. Immunohistochemistry showed that following TAM treatment only ∼20% of GFAP-labeled cells in the retrotrapazoid nucleus and in the raphé magnus were positive for MeCP2. The slope of the relative increase in minute ventilation as a function of 1, 3, and 5% inspired CO2 was depressed in mice with depleted astrocyte MeCP2 compared with wild-type littermates. In contrast, selective depletion of MeCP2 in neurons did not significantly affect slope. While neurons which constitute the respiratory network ultimately determine the ventilatory response to CO2, this study demonstrates that loss of MeCP2 in astrocytes alone is sufficient to result in a dramatic attenuation of the HCVR. We propose that the glial contribution to HCVR is under the control of the MeCP2 gene.

scholarly journals Lethal avian influenza A (H5N1) virus replicates in pontomedullary chemosensitive neurons and depresses hypercapnic ventilatory response in mice

2019 ◽  
Vol 316 (3) ◽  
pp. L525-L536 ◽  
Author(s):  
Jianguo Zhuang ◽  
Na Zang ◽  
Chunyan Ye ◽  
Fadi Xu
Keyword(s):  
Viral Infection ◽  
Carotid Body ◽  
Influenza A ◽  
Tryptophan Hydroxylase ◽  
Ventilatory Response ◽  
Severe Depression ◽  
Infection Period ◽  
Hypercapnic Ventilatory Response ◽  
H5n1 Influenza ◽  
Neurokinin 1

The highly pathogenic H5N1 (HK483) viral infection causes a depressed hypercapnic ventilatory response (dHCVR, 20%↓) at 2 days postinfection (dpi) and death at 7 dpi in mice, but the relevant mechanisms are not fully understood. Glomus cells in the carotid body and catecholaminergic neurons in locus coeruleus (LC), neurokinin 1 receptor (NK1R)-expressing neurons in the retrotrapezoid nucleus (RTN), and serotonergic neurons in the raphe are chemosensitive and responsible for HCVR. We asked whether the dHCVR became worse over the infection period with viral replication in these cells/neurons. Mice intranasally inoculated with saline or the HK483 virus were exposed to hypercapnia for 5 min at 0, 2, 4, or 6 dpi, followed by immunohistochemistry to determine the expression of nucleoprotein of H5N1 influenza A (NP) alone and coupled with 1) tyrosine hydroxylase (TH) in the carotid body and LC, 2) NK1R in the RTN, and 3) tryptophan hydroxylase (TPH) in the raphe. HK483 viral infection blunted HCVR by ∼20, 50, and 65% at 2, 4, and 6 dpi. The NP was observed in the pontomedullary respiratory-related nuclei (but not in the carotid body) at 4 and 6 dpi, especially in 20% of RTN NK1R, 35% of LC TH, and ∼10% raphe TPH neurons. The infection significantly reduced the local NK1R or TPH immunoreactivity and population of neurons expressing NK1R or TPH. We conclude that the HK483 virus infects the pontomedullary respiratory nuclei, particularly chemosensitive neurons in the RTN, LC, and raphe, contributing to the severe depression of HCVR and respiratory failure at 6 dpi.

Ventilatory responses to carbon dioxide at low and high levels of oxygen are elevated after episodic hypoxia in men compared with women

2004 ◽  
Vol 97 (5) ◽  
pp. 1673-1680 ◽  
Author(s):  
Chris Morelli ◽  
M. Safwan Badr ◽  
Jason H. Mateika
Keyword(s):  
Carbon Dioxide ◽  
Ventilatory Response ◽  
Minute Ventilation ◽  
High Oxygen ◽  
Set Point ◽  
Ventilatory Responses ◽  
Episodic Hypoxia ◽  
Before And After ◽  
Oxygen Gas ◽  
End Tidal

We hypothesized that the acute ventilatory response to carbon dioxide in the presence of low and high levels of oxygen would increase to a greater extent in men compared with women after exposure to episodic hypoxia. Eleven healthy men and women of similar race, age, and body mass index completed a series of rebreathing trials before and after exposure to eight 4-min episodes of hypoxia. During the rebreathing trials, subjects initially hyperventilated to reduce the end-tidal partial pressure of carbon dioxide (PetCO2) below 25 Torr. Subjects then rebreathed from a bag containing a normocapnic (42 Torr), low (50 Torr), or high oxygen gas mixture (150 Torr). During the trials, PetCO2 increased while the selected level of oxygen was maintained. The point at which minute ventilation began to rise in a linear fashion as PetCO2 increased was considered to be the carbon dioxide set point. The ventilatory response below and above this point was determined. The results showed that the ventilatory response to carbon dioxide above the set point was increased in men compared with women before exposure to episodic hypoxia, independent of the oxygen level that was maintained during the rebreathing trials (50 Torr: men, 5.19 ± 0.82 vs. women, 4.70 ± 0.77 l·min−1·Torr−1; 150 Torr: men, 4.33 ± 1.15 vs. women, 3.21 ± 0.58 l·min−1·Torr−1). Moreover, relative to baseline measures, the ventilatory response to carbon dioxide in the presence of low and high oxygen levels increased to a greater extent in men compared with women after exposure to episodic hypoxia (50 Torr: men, 9.52 ± 1.40 vs. women, 5.97 ± 0.71 l·min−1·Torr−1; 150 Torr: men, 5.73 ± 0.81 vs. women, 3.83 ± 0.56 l·min−1·Torr−1). Thus we conclude that enhancement of the acute ventilatory response to carbon dioxide after episodic hypoxia is sex dependent.

scholarly journals Benefit and Risk Evaluation of Biased μ-Receptor Agonist Oliceridine versus Morphine

2020 ◽  
Vol 133 (3) ◽  
pp. 559-568 ◽  
Author(s):  
Albert Dahan ◽  
C. Jan van Dam ◽  
Marieke Niesters ◽  
Monique van Velzen ◽  
Michael J. Fossler ◽  
...  
Keyword(s):  
Utility Function ◽  
Respiratory Depression ◽  
Receptor Agonist ◽  
Ventilatory Response ◽  
Cold Pressor Test ◽  
Cold Pressor ◽  
Population Pharmacokinetic ◽  
Potency Ratio ◽  
Analgesic Effects ◽  
Hypercapnic Ventilatory Response

Background To improve understanding of the respiratory behavior of oliceridine, a μ-opioid receptor agonist that selectively engages the G-protein–coupled signaling pathway with reduced activation of the β-arrestin pathway, the authors compared its utility function with that of morphine. It was hypothesized that at equianalgesia, oliceridine will produce less respiratory depression than morphine and that this is reflected in a superior utility. Methods Data from a previous trial that compared the respiratory and analgesic effects of oliceridine and morphine in healthy male volunteers (n = 30) were reanalyzed. A population pharmacokinetic–pharmacodynamic analysis was performed and served as basis for construction of utility functions, which are objective functions of probability of analgesia, P(analgesia), and probability of respiratory depression, P(respiratory depression). The utility function = P(analgesia ≥ 0.5) – P(respiratory depression ≥ 0.25), where analgesia ≥ 0.5 is the increase in hand withdrawal latency in the cold pressor test by at least 50%, and respiratory depression ≥ 0.25 is the decrease of the hypercapnic ventilatory response by at least 25%. Values are median ± standard error of the estimate. Results The two drugs were equianalgesic with similar potency values (oliceridine: 27.9 ± 4.9 ng/ml; morphine 34.3 ± 9.7 ng/ml; potency ratio, 0.81; 95% CI, 0.39 to 1.56). A 50% reduction of the hypercapnic ventilatory response by morphine occurred at an effect-site concentration of 33.7 ± 4.8 ng/ml, while a 25% reduction by oliceridine occurred at 27.4 ± 3.5 ng/ml (potency ratio, 2.48; 95% CI, 1.65 to 3.72; P < 0.01). Over the clinically relevant concentration range of 0 to 35 ng/ml, the oliceridine utility function was positive, indicating that the probability of analgesia exceeds the probability of respiratory depression. In contrast, the morphine function was negative, indicative of a greater probability of respiratory depression than analgesia. Conclusions These data indicate a favorable oliceridine safety profile over morphine when considering analgesia and respiratory depression over the clinical concentration range. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Disordered Leptin signaling in the retrotrapezoid nucleus is associated with the impaired hypercapnic ventilatory response in obesity

Life Sciences ◽  
2020 ◽  
Vol 257 ◽  
pp. 117994
Author(s):  
Ziqian Wei ◽  
Yinchao Hao ◽  
Hongxiao Yu ◽  
Luo Shi ◽  
Xinyi Jing ◽  
...  
Keyword(s):  
Ventilatory Response ◽  
Leptin Signaling ◽  
Hypercapnic Ventilatory Response ◽  
Retrotrapezoid Nucleus

Peripheral chemoreflex responsiveness is increased at elevated levels of carbon dioxide after episodic hypoxia in awake humans

2004 ◽  
Vol 96 (3) ◽  
pp. 1197-1205 ◽  
Author(s):  
Jason H. Mateika ◽  
Chris Mendello ◽  
Dany Obeid ◽  
M. Safwan Badr
Keyword(s):  
Carbon Dioxide ◽  
Ventilatory Response ◽  
High Oxygen ◽  
Recruitment Threshold ◽  
Episodic Hypoxia ◽  
Before And After ◽  
Carbon Dioxide Levels ◽  
Peripheral Chemoreflex ◽  
Long Term Facilitation ◽  
Ventilatory Response To Hypoxia

We hypothesized that the acute ventilatory response to hypoxia is enhanced after exposure to episodic hypoxia in awake humans. Eleven subjects completed a series of rebreathing trials before and after exposure to eight 4-min episodes of hypoxia. During the rebreathing trials, subjects initially hyperventilated to reduce the partial pressure of carbon dioxide (PetCO2) below 25 Torr. Subjects then breathed from a bag containing normocapnic (42 Torr), low (50 Torr), or high oxygen (140 Torr) gas mixtures. During the trials, PetCO2 increased while a constant oxygen level was maintained. The point at which ventilation began to rise in a linear fashion as PetCO2 increased was considered to be the ventilatory recruitment threshold. The ventilatory response below and above the recruitment threshold was determined. Ventilation did not persist above baseline values immediately after exposure to episodic hypoxia; however, PetCO2 levels were reduced compared with baseline. In contrast, compared with baseline, the ventilatory response to progressive increases in carbon dioxide during rebreathing trials in the presence of low but not high oxygen levels was increased after exposure to episodic hypoxia. This increase occurred when carbon dioxide levels were above but not below the ventilatory recruitment threshold. We conclude that long-term facilitation of ventilation (i.e., increases in ventilation that persist when normoxia is restored after episodic hypoxia) is not expressed in awake humans in the presence of hypocapnia. Nevertheless, despite this lack of expression, the acute ventilatory response to hypoxia in the presence of hypercapnia is increased after exposure to episodic hypoxia.

Effects of Chronic Acid-Base Changes on the Rebreathing Hypercapnic Ventilatory Response in Man

Respiration ◽  
1991 ◽  
Vol 58 (3-4) ◽  
pp. 181-185 ◽  
Author(s):  
Ami Oren ◽  
Brian J. Whipp ◽  
Karlman Wasserman
Keyword(s):  
Ventilatory Response ◽  
Acid Base ◽  
Hypercapnic Ventilatory Response
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