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1.
Brain Res ; 1791: 147995, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-35779583

RESUMO

Growth hormone (GH)-responsive neurons regulate several homeostatic behaviors including metabolism, energy balance, arousal, and stress response. Therefore, it is possible that GH-responsive neurons play a role in other responses such as CO2/H+-dependent breathing behaviors. Here, we investigated whether central GH receptor (GHR) modulates respiratory activity in conscious unrestrained mice. First, we detected clusters of GH-responsive neurons in the tyrosine hydroxylase-expressing cells in the rostroventrolateral medulla (C1 region) and within the locus coeruleus (LC). No significant expression was detected in phox2b-expressing cells in the retrotrapezoid nucleus. Whole body plethysmography revealed a reduction in the tachypneic response to hypoxia (FiO2 = 0.08) without changing baseline breathing and the hypercapnic ventilatory response. Contrary to the physiological findings, we did not find significant differences in the number of fos-activated cells in the nucleus of the solitary tract (NTS), C1, LC and paraventricular nucleus of the hypothalamus (PVH). Our finding suggests a possible secondary role of central GH action in the tachypneic response to hypoxia in conscious mice.


Assuntos
Hipercapnia , Núcleo Solitário , Animais , Hormônio do Crescimento/metabolismo , Hipotálamo/metabolismo , Hipóxia/metabolismo , Camundongos , Núcleo Solitário/metabolismo
2.
J Appl Physiol (1985) ; 133(2): 461-470, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35796612

RESUMO

The acute effect of exercise intensity on cerebrovascular reactivity and whether this mirrors changes in peripheral vascular function have not been investigated. The aim of this study was to explore the acute effect of exercise intensity on cerebrovascular reactivity (CVR) and peripheral vascular function in healthy young adults (n = 10, 6 females, 22.7 ± 3.5 yr). Participants completed four experimental conditions on separate days: high-intensity interval exercise (HIIE) with intervals performed at 75% maximal oxygen uptake (V̇o2max; HIIE1), HIIE with intervals performed at 90% V̇o2max (HIIE2), continuous moderate-intensity exercise (MIE) at 60% V̇o2max and a sedentary control condition (CON). All exercise conditions were completed on a cycle ergometer and matched for time (30 min) and average intensity (60% V̇o2max). Brachial artery flow-mediated dilation (FMD) and CVR of the middle cerebral artery were measured before exercise, and 1- and 3-h after exercise. CVR was assessed using transcranial Doppler ultrasonography to both hypercapnia (6% carbon dioxide breathing) and hypocapnia (hyperventilation). FMD was significantly elevated above baseline 1 and 3 h following both HIIE conditions (P < 0.05), but FMD was unchanged following the MIE and CON trials (P > 0.33). CVR to both hypercapnia and hypocapnia, and when expressed across the end-tidal CO2 range, was unchanged in all conditions, at all time points (all P > 0.14). In conclusion, these novel findings show that the acute increases in peripheral vascular function following HIIE, compared with MIE, were not mirrored by changes in cerebrovascular reactivity, which was unaltered following all exercise conditions in healthy young adults.NEW & NOTEWORTHY This is the first study to identify that acute improvements in peripheral vascular function following high-intensity interval exercise are not mirrored by improvements in cerebrovascular reactivity in healthy young adults. High-intensity interval exercise completed at both 75% and 90% V̇o2max increased brachial artery flow-mediated dilation 1 and 3 h following exercise, compared with continuous moderate-intensity exercise and a sedentary control condition. By contrast, cerebrovascular reactivity was unchanged following all four conditions.


Assuntos
Hipercapnia , Hipocapnia , Artéria Braquial , Circulação Cerebrovascular , Endotélio Vascular , Exercício Físico , Feminino , Humanos , Adulto Jovem
3.
Eur J Anaesthesiol ; 39(9): 774-784, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35852545

RESUMO

BACKGROUND: Regional cerebrovascular reactivity (rCVR) is highly variable in the human brain as measured by blood oxygenation level-dependent (BOLD) MRI to changes in both end-tidal CO 2 and O 2 . OBJECTIVES: We examined awake participants under carefully controlled end-tidal gas concentrations to assess how regional CVR changes may present with end-tidal gas changes seen commonly with anaesthesia. DESIGN: Observational study. SETTING: Tertiary care centre, Winnipeg, Canada. The imaging for the study occurred in 2019. SUBJECTS: Twelve healthy adult subjects. INTERVENTIONS: Cerebral BOLD response was studied under two end-tidal gas paradigms. First end-tidal oxygen (ETO 2 ) maintained stable whereas ETCO 2 increased incrementally from hypocapnia to hypercapnia (CO 2 ramp); second ETCO 2 maintained stable whereas ETO 2 increased from normoxia to hyperoxia (O 2 ramp). BOLD images were modeled with end-tidal gas sequences split into two equal segments to examine regional CVR. MAIN OUTCOME MEASURES: The voxel distribution comparing hypocapnia to mild hypercapnia and mild hyperoxia (mean F I O 2  = 0.3) to marked hyperoxia (mean F I O 2  = 0.7) were compared in a paired fashion ( P  < 0.005 to reach threshold for voxel display). Additionally, type analysis was conducted on CO 2 ramp data. This stratifies the BOLD response to the CO 2 ramp into four categories of CVR slope based on segmentation (type A; +/+slope: normal response, type B +/-, type C -/-: intracranial steal, type D -/+.) Types B to D represent altered responses to the CO 2 stimulus. RESULTS: Differential regional responsiveness was seen for both end-tidal gases. Hypocapnic regional CVR was more marked than hypercapnic CVR in 0.3% of voxels examined ( P  < 0.005, paired comparison); the converse occurred in 2.3% of voxels. For O 2 , mild hyperoxia had more marked CVR in 0.2% of voxels compared with greater hyperoxia; the converse occurred in 0.5% of voxels. All subjects had altered regional CO 2 response based on Type Analysis ranging from 4 ±â€Š2 to 7 ±â€Š3% of voxels. CONCLUSION: In awake subjects, regional differences and abnormalities in CVR were observed with changes in end-tidal gases common during the conduct of anaesthesia. On the basis of these findings, consideration could be given to minimising regional CVR fluctuations in patients-at-risk of neurological complications by tighter control of end-tidal gases near the individual's resting values.


Assuntos
Anestesia , Hiperóxia , Adulto , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Dióxido de Carbono , Circulação Cerebrovascular/fisiologia , Gases , Humanos , Hipercapnia , Hipocapnia/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Oxigênio , Vigília
4.
Physiol Rep ; 10(13): e15373, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35822289

RESUMO

Women experience fluctuating orthostatic intolerance during the menstrual cycle, suggesting sex hormones may influence cerebral blood flow. Young (aged 18-30) healthy women, either taking oral contraceptives (OC; n = 14) or not taking OC (NOC; n = 12), were administered hypercapnic gas (5%) for 5 min in the low hormone (LH; placebo pill) and high hormone (HH; active pill) menstrual phases. Hemodynamic and cerebrovascular variables were continuously measured. Cerebral blood velocity changes were monitored using transcranial doppler ultrasound of the middle cerebral artery to determine cerebrovascular reactivity. Cerebral autoregulation was assessed using steady-state analysis (static cerebral autoregulation) and transfer function analysis (dynamic cerebral autoregulation; dCA). In response to hypercapnia, menstrual phase did not influence static cardiovascular or cerebrovascular responses (all p > 0.07); however, OC users had a greater increase of mean middle cerebral artery blood velocity compared to NOC (NOC-LH 12 ± 6 cm/s vs. NOC-HH 16 ± 9 cm/s; OC-LH 18 ± 5 cm/s vs. OC-HH 17 ± 11 cm/s; p = 0.048). In all women, hypercapnia improved high frequency (HF) and very low frequency (VLF) cerebral autoregulation (decreased nGain; p = 0.002 and <0.001, respectively), whereas low frequency (LF) Phase decreased in NOC-HH (p = 0.001) and OC-LH (p = 0.004). Therefore, endogenous sex hormones reduce LF dCA during hypercapnia in the HH menstrual phase. In contrast, pharmaceutical sex hormones (OC use) have no acute influence (HH menstrual phase) yet elicit a chronic attenuation of LF dCA (LH menstrual phase) during hypercapnia.


Assuntos
Hipercapnia , Ciclo Menstrual , Anticoncepcionais Orais/farmacologia , Feminino , Hormônios Esteroides Gonadais , Humanos , Ciclo Menstrual/fisiologia , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/fisiologia
5.
Int J Chron Obstruct Pulmon Dis ; 17: 1553-1563, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35832833

RESUMO

Purpose: An episodic increase in transcutaneous carbon dioxide pressure (PtcCO2) is often recognized in patients with advanced chronic obstructive pulmonary disease (COPD) by overnight PtcCO2 monitoring. This phenomenon, called episodic nocturnal hypercapnia (eNH), mainly corresponds to rapid eye movement (REM) sleep-related hypoventilation. However, it is unclear whether eNH is associated with the frequency of COPD exacerbation. We aimed to investigate whether a relationship exists between COPD exacerbation and eNH. Patients and Methods: We enrolled consecutive patients with stable, severe, or very severe COPD with a daytime arterial carbon dioxide pressure (PaCO2) <55.0 mmHg who underwent overnight PtcCO2 monitoring from April 2013 to January 2017. We retrospectively analyzed the prevalence of eNH and sleep-associated hypoventilation (SH) as defined by the American Academy of Sleep Medicine. Moreover, we compared the relationship between the frequency of COPD exacerbations in the previous year and eNH or SH. Results: Twenty-four patients were included in this study. The study patients had a mean daytime PaCO2 and nocturnal PtcCO2 of 43.3 ± 6.8 mmHg and 42.9 ± 9.6 mmHg, respectively. Six (25.0%) and 11 (45.9%) of the 24 patients met the SH and eNH criteria, respectively. The odds ratios of SH and eNH for at least one annual exacerbation were 1.0 [95% confidence interval (CI): 0.16-6.00] and 11.1 [95% CI: 1.39-87.7], respectively. The odds ratios of SH and eNH for at least two annual exacerbations were 0.3 [95% CI: 0.04-2.64] and 6.6 [95% CI: 1.06-39.4], respectively. Conclusion: In patients with advanced COPD and a daytime PaCO2 <55.0 mmHg, eNH may be associated with a history of more frequent exacerbations than SH. Further studies are required to validate these findings.


Assuntos
Hipercapnia , Doença Pulmonar Obstrutiva Crônica , Dióxido de Carbono , Humanos , Hipercapnia/complicações , Hipercapnia/diagnóstico , Hipercapnia/epidemiologia , Hipoventilação/complicações , Hipoventilação/epidemiologia , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Estudos Retrospectivos
6.
Tuberk Toraks ; 70(2): 157-165, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35785880

RESUMO

Introduction: Non-invasive mechanical ventilation (NIMV) is a successful treatment modality in hypercapnic respiratory failure. Patient compliance and mask selection are the most important factors in the success of NIMV. In our prospective randomized study, we aimed to investigate the efficacy of full-face and oronasal masks in the treatment of patients with hypercapnic respiratory failure who underwent NIMV and to investigate the mask compliance of the patients. Materials and Methods: In this prospective randomized study, 60 patients with hypercapnic respiratory failure were divided into two groups; the full face mask group (n= 30) and the oronasal mask group (n= 30). Arterial blood gas values and respiratory rates were measured before the treatment and at the 1st, 6th, 24th, and 72nd hours of the treatment. The compliance of the patients with the treatment was evaluated with the patient compliance scale (PCS) at the 1st, 6th, and 24th hours of the treatment. Result: Eight patients from the full-face mask group were excluded because of mask-face mismatch and claustrophobia, and two patients from the oronasal mask group due to persistent hypercapnia. In the full face mask group, improvement in pH was observed at the 1st and 24th hours of treatment (p= 0.042, p= 0.033), and PCO2 decreased at the 72nd hour of treatment (p= 0.024). There was no difference in patient compliance and respiratory rate between groups. The complaints of burning sensation and pressure in the eyes were higher in the full face mask group (p= 0.025), and pressure ulcers were more common in the oronasal mask group (p= 0.025). Conclusions: The reduction in PCO2 and improvement in pH were greater with a full face mask. Pressure sores were less common with a full face mask. In our study, no difference was found in terms of patient compliance between groups. It should be noted that choosing a full face mask in patients with high compliance will increase the success in the treatment of hypercapnic respiratory failure.


Assuntos
Respiração Artificial , Insuficiência Respiratória , Humanos , Hipercapnia/terapia , Máscaras , Estudos Prospectivos , Insuficiência Respiratória/terapia
7.
Braz J Anesthesiol ; 72(3): 398-406, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35644204

RESUMO

BACKGROUND: The effect of mild changes in CO2 levels to organ perfusion and tissue inflammation are well known, whereas an influence of hypercapnia under general anesthesia on adverse events as nausea and vomiting, or length of hospital stay is barely examined. The goal of our meta-analysis was to identify possibly positive effects of hypercapnia versus normocapnia in general anesthesia in adult patients. METHODS: We conducted a systematic review of parallel-arm randomised controlled trials comparing hypercapnia versus normocapnia in adult patients undergoing general anesthesia. In July 2018 and September 2019 we searched "CENTRAL‿, "MEDLINE‿, and "Embase‿, checked reference lists of all included studies and relevant systematic reviews for additional references to trials. Two review authors independently assessed trials for inclusion, extracted data, and completed a "Risk of bias‿ assessment for all included studies. RESULTS: Our search identified 297 records after abstract screening 30 full-text papers remained for further examination. Ten publications met our inclusion criteria and were used for narrative description of this systematic review. Three studies were eligible for the meta-analysis normocapnia versus hypercapnia with the outcomes: time to extubation and adverse events. On average, time to extubation was significantly reduced in the hypercapnia group with a mean difference 3.78 (95% CI 0.85 to 6.71). No difference was found regarding adverse events. CONCLUSIONS: The findings of our study do not enable us to produce evidence of a positive influence of increased CO2 partial pressure levels during general anesthesia. A well-planned, adequately powered randomized controlled trial would be desirable in the future.


Assuntos
Dióxido de Carbono , Hipercapnia , Adulto , Anestesia Geral/efeitos adversos , Humanos
8.
J Physiol ; 600(16): 3671-3688, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35710103

RESUMO

The cardiovascular response resulting from the individual activation of the muscle mechanoreflex (MMR) or the chemoreflex (CR) is different between men and women. Whether the haemodynamic consequence resulting from the interaction of these sympathoexcitatory reflexes is also sex-dependent remains unknown. MMR and CR were activated by passive leg movement (LM) and exposure to hypoxia (O2 -CR) or hypercapnia (CO2 -CR), respectively. Twelve young men and 12 young women completed two experimental protocols: (1) resting in normoxia (PET O2 : ∼83 mmHg, PET CO2 : ∼34 mmHg), normocapnic hypoxia (PET O2 : ∼48 mmHg, PET CO2 : ∼34 mmHg) and hyperoxic hypercapnia (PET O2 : ∼524 mmHg, PET CO2 : ∼44 mmHg); (2) LM under the same gas conditions. During the MMR:O2 -CR coactivation, in men, the observed mean arterial pressure (MAP) and cardiac output (CO) were not different (additive effect), while the observed leg blood flow (LBF) and vascular conductance (LVC) were significantly lower (hypo-additive), compared with the sum of the responses elicited by each reflex alone. In women, the observed MAP was not different (additive) while the observed CO, LBF and LVC were significantly greater (hyper-additive), compared with the summated responses. During the MMR:CO2 -CR coactivation, in men, the observed MAP, CO and LBF were not different (additive), while the observed LVC was significantly lower (hypo-additive), compared with the summated responses. In women, the observed MAP was significantly higher (hyper-additive), while the observed CO, LBF and LVC were not different (additive), compared with the summated responses. The interaction of the MMR and CR has a pronounced influence on the autonomic cardiovascular control, with the haemodynamic consequences differing between men and women. KEY POINTS: The cardiovascular response resulting from the activation of the muscle mechanoreflex (MMR) or the chemoreflex (CR) was previously shown to be different between women and men; this study focused on the haemodynamic consequence of the interaction of these two sympathoexcitatory reflexes. MMR and CR were activated by passive leg movement and exposure to hypoxia (O2 -CR) or hypercapnia (CO2 -CR), respectively. Individual and interactive reflex effects on central and peripheral haemodynamics were quantified in healthy young women and men. In men, the MMR:O2 -CR and MMR:CO2 -CR interactions restricted peripheral haemodynamics, likely by potentiating sympathetic vasoconstriction. In women, the MMR:O2 -CR interaction facilitated central and peripheral haemodynamics, likely by potentiating sympathetic vasodilatation; however, the MMR:CO2 -CR interaction was simply additive for the central and peripheral haemodynamics. The interaction between the MMR and the CR exerts a profound influence on the autonomic control of cardiovascular function in humans, with the haemodynamic consequences differing between women and men.


Assuntos
Dióxido de Carbono , Hipercapnia , Feminino , Hemodinâmica , Humanos , Hipóxia , Masculino , Músculos
9.
Int J Mol Sci ; 23(11)2022 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-35682682

RESUMO

Despite the severe respiratory problems reducing the quality of life for Alzheimer's disease (AD) patients, their causes are poorly understood. We aimed to investigate hypoxic and hypercapnic respiratory responses in a transgenic mouse model of AD (AßPP V717I) overexpressing AßPP and mimicking early-onset AD. The cholinesterase inhibitor rivastigmine and the NMDA receptor antagonist memantine were used to investigate the effects of drugs, used to treat AD cognitive dysfunction, on breathing in hypoxia and hypercapnia. We found a significant increase in the respiratory response to hypercapnia and no difference in the hypoxic response in APP+ mice, compared with the control group (APP-). Memantine had no effect on respiration in either group, including responses to hypoxia and hypercapnia. Rivastigmine depressed resting ventilation and response to hypercapnia irrespective of the mice genotype. Reduction in hypoxia-augmented ventilation by rivastigmine was observed only in APP+ mice, which exhibited lower acetylcholinesterase activity in the hippocampus. Treatment with rivastigmine reduced the enzyme activity in both groups equally in the hippocampus and brainstem. The increased ventilatory response to hypercapnia in transgenic mice may indicate alterations in chemoreceptive respiratory nuclei, resulting in increased CO2 sensitivity. Rivastigmine is a potent reductant of normoxic and hypercapnic respiration in APP+ and APP- mice.


Assuntos
Doença de Alzheimer , Memantina , Acetilcolinesterase , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Animais , Modelos Animais de Doenças , Humanos , Hipercapnia/tratamento farmacológico , Hipóxia/tratamento farmacológico , Memantina/farmacologia , Memantina/uso terapêutico , Camundongos , Camundongos Transgênicos , Qualidade de Vida , Respiração , Rivastigmina/farmacologia , Rivastigmina/uso terapêutico
11.
Commun Biol ; 5(1): 642, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35768580

RESUMO

The hypoxic ventilatory response (HVR) is critical to breathing and thus oxygen supply to the body and is primarily mediated by the carotid bodies. Here we reveal that carotid body afferent discharge during hypoxia and hypercapnia is determined by the expression of Liver Kinase B1 (LKB1), the principal kinase that activates the AMP-activated protein kinase (AMPK) during metabolic stresses. Conversely, conditional deletion in catecholaminergic cells of AMPK had no effect on carotid body responses to hypoxia or hypercapnia. By contrast, the HVR was attenuated by LKB1 and AMPK deletion. However, in LKB1 knockouts hypoxia evoked hypoventilation, apnoea and Cheyne-Stokes-like breathing, while only hypoventilation and apnoea were observed after AMPK deletion. We therefore identify LKB1 as an essential regulator of carotid body chemosensing and uncover a divergence in dependency on LKB1 and AMPK between the carotid body on one hand and the HVR on the other.


Assuntos
Quinases Proteína-Quinases Ativadas por AMP , Proteínas Quinases Ativadas por AMP , Corpo Carotídeo , Hipóxia , Quinases Proteína-Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Apneia , Corpo Carotídeo/metabolismo , Humanos , Hipercapnia/metabolismo , Hipoventilação/metabolismo , Hipóxia/metabolismo
12.
Respiration ; 101(8): 709-716, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35717945

RESUMO

Advanced chronic obstructive pulmonary disease (COPD) might result in chronic hypercapnic ventilatory failure. Similar to neuromuscular and restrictive chest wall diseases, long-term non-invasive positive pressure ventilation (NPPV) is increasingly used in chronic hypercapnic COPD. This review describes the methods, patient selection, ventilatory strategies, and therapeutic effects of long-term Home-NPPV based on randomized controlled clinical trials published since 1985 in English language retrieved from the databases PubMed and Scopus. Long-term NPPV is feasible and effective in stable, non-exacerbated COPD patients with daytime hypercapnia with arterial pressure of carbon dioxide (PaCO2) levels ≥50 mm Hg (6.6 kPa), if the applied ventilatory pressures and application times improve baseline hypercapnia by at least 20%. Patients who survived an acute hypercapnic exacerbation might benefit from long-term NPPV if hypercapnia persists 2-4 weeks after resolution of the exacerbation. Pressure-controlled ventilation or pressure-support ventilation with adequate minimum backup breathing frequencies, in combination with nasal masks or oronasal masks have been successfully used in all larger clinical trials. Ventilatory strategies with mean inspiratory pressures of up to 28 cm H2O are well-tolerated by patients, but limitations exist in patients with impaired cardiac performance. Home-NPPV with a PaCO2-reductive approach might be considered as an additional treatment option in patients with stable chronic hypercapnic COPD.


Assuntos
Ventilação não Invasiva , Doença Pulmonar Obstrutiva Crônica , Insuficiência Respiratória , Humanos , Hipercapnia/etiologia , Hipercapnia/terapia , Ventilação não Invasiva/métodos , Respiração com Pressão Positiva/métodos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/terapia , Insuficiência Respiratória/terapia
13.
J Appl Physiol (1985) ; 133(2): 371-389, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35708704

RESUMO

Serotonin (5-HT) is an important modulator of brain networks that control breathing. The selective serotonin reuptake inhibitor fluoxetine (FLX) is the first-line antidepressant drug prescribed during pregnancy. We investigated the effects of prenatal FLX exposure on baseline breathing, ventilatory and metabolic responses to hypercapnia and hypoxia as well as number of brainstem 5-HT and tyrosine hydroxylase (TH) neurons of rats during postnatal development (P0-82). Prenatal FLX exposure of males showed a lower baseline V̇e that appeared in juveniles and remained in adulthood, with no sleep-wake state dependency. Prenatal FLX exposure of females did not affect baseline breathing. Juvenile male FLX showed increased CO2 and hypoxic ventilatory responses, normalizing by adulthood. Alterations in juvenile FLX-treated males were associated with a greater number of 5-HT neurons in the raphe obscurus (ROB) and raphe magnus (RMAG). Adult FLX-exposed males showed greater number of 5-HT neurons in the raphe pallidus (RPA) and TH neurons in the A5, whereas reduced number of TH neurons in A7. Prenatal FLX exposure of female rats was associated with greater hyperventilation induced by hypercapnia at P0-2 and juveniles, whereas P12-14 and adult FLX (non-rapid eye movement, NREM sleep) rats showed an attenuation of the hyperventilation induced by CO2. FLX-exposed females had fewer 5-HT neurons in the RPA and reduced TH A6 density at P0-2; and greater number of TH neurons in the A7 at P12-14. These data indicate that prenatal FLX exposure affects the number of some monoaminergic regions in the brain and results in long-lasting, sex-specific changes in baseline breathing pattern and ventilatory responses to respiratory challenges.NEW & NOTEWORTHY Selective serotonin reuptake inhibitors (SSRIs) readily cross the placental and the fetal blood-brain barrier where it will affect 5-HT levels in the developing brain. Although SSRI is used during pregnancy, there are no studies showing SSRI exposure during late pregnancy and postnatal effects on breathing control in males and females. We demonstrated that fluoxetine exposure during late pregnancy in rats was associated with long-lasting, sex-specific effects on breathing and brainstem monoaminergic groups.


Assuntos
Fluoxetina , Efeitos Tardios da Exposição Pré-Natal , Animais , Dióxido de Carbono , Feminino , Fluoxetina/farmacologia , Humanos , Hipercapnia , Hiperventilação , Masculino , Placenta/metabolismo , Gravidez , Ratos , Serotonina/metabolismo , Inibidores de Captação de Serotonina/farmacologia
14.
Can Respir J ; 2022: 2321909, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35762008

RESUMO

Introduction: Respiratory insufficiency is one of the main causes of death in myotonic dystrophy type 1 (DM1). Although there is general consensus that these patients have a restrictive ventilatory pattern, hypoventilation, chronic hypercapnia, and sleep disturbances, the prevalence of respiratory disease and indication for the effects of noninvasive ventilation (NIV) need to be further explored. Objectives: To describe respiratory function and need for NIV at baseline and over time in a cohort of adult patients with DM1. Methods: A total of 151 adult patients with DM1 were subjected to arterial blood gas analysis, sitting and supine forced vital capacity (FVC), peak cough expiratory flow (PCEF), nocturnal oximetry, and maximal inspiratory pressure and expiratory pressure (MIP/PEP). Results: On first assessment, 84 of 151 had normal respiratory function (median age: 38 years, median BMI: 23.9, and median disease duration: 11 years); 67 received an indication to use NIV (median age: 49 years, median BMI: 25,8, and median disease duration: 14 years). After a median time of 3.85 years, 43 patients were lost to follow-up; 9 of 84 required NIV; only 17 of 67 with the new NIV prescription were adherent. Conclusions: We provide additional data on the natural history of respiratory function decline and treatment adherence in a relatively large cohort of well-characterized patients with DM1. A high proportion (28%) was lost to follow-up. A minority (11%) required NIV, and only 25% were treatment adherent, irrespective of specific demographics and respiratory features. Our results also confirm previous findings, showing that age, disease duration, and higher BMIs are predisposing factors for respiratory impairment.


Assuntos
Distrofia Miotônica , Ventilação não Invasiva , Insuficiência Respiratória , Adulto , Humanos , Hipercapnia/etiologia , Hipercapnia/terapia , Pessoa de Meia-Idade , Distrofia Miotônica/complicações , Distrofia Miotônica/terapia , Respiração , Insuficiência Respiratória/terapia
15.
Acta Physiol (Oxf) ; 235(4): e13849, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35665450

RESUMO

AIM: Although zebrafish are gaining popularity as biomedical models of cardiovascular disease, our understanding of their cardiac control mechanisms is fragmentary. Our goal was to clarify the controversial role of the ß1-adrenergic receptor (AR) in the regulation of heart rate in zebrafish. METHODS: CRISPR-Cas9 was used to delete the adrb1 gene in zebrafish allowing us to generate a stable adrb1-/- line. Larval heart rates were measured during pharmacological protocols and with exposure to hypercapnia. Expression of the five zebrafish adrb genes were measured in larval zebrafish hearts using qPCR. RESULTS: Compared with genetically matched wild-types (adrb1+/+ ), adrb1-/- larvae exhibited ~20 beats min-1 lower heart rate, measured from 2 to 21 days post-fertilization (dpf). Nevertheless, adrb1-/- larvae exhibited preserved positive chronotropic responses to pharmacological treatment with AR agonists (adrenaline, noradrenaline, isoproterenol), which were blocked by propranolol (general ß-AR antagonist). Regardless of genotype, larvae exhibited similar increases in heart rate in response to hypercapnia (1% CO2 ) at 5 dpf, but tachycardia was blunted in adrb1-/- larvae at 6 dpf. adrb1 gene expression was abolished in the hearts of adrb1-/- larvae, confirming successful knockout. While gene expression of adrb2a and adrb3a was unchanged, adrb2b and adrb3b mRNA levels increased in adrb1-/- larval hearts. CONCLUSION: Despite adrb1 contributing to the setting of resting heart rate in larvae, it is not strictly essential for zebrafish, as we generated a viable and breeding adrb1-/- line. The chronotropic effects of adrenergic stimulation persist in adrb1-/- zebrafish, likely due to the upregulation of other ß-AR subtypes.


Assuntos
Hipercapnia , Peixe-Zebra , Animais , Coração , Frequência Cardíaca/fisiologia , Larva/genética , Larva/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismo
16.
Biomed Khim ; 68(3): 212-217, 2022 Jun.
Artigo em Russo | MEDLINE | ID: mdl-35717585

RESUMO

The aim of this work is to study of ozone effect on blood oxygen-dependent processes under hypercapnia conditions. The studied blood samples are pretreated with a hypercapnic gas mixture followed by the addition of ozonized isotonic sodium chloride solution (with an ozone concentration of 6 mg/l), as well as gaseous transmitters donors, nitroglycerin and sodium hydrosulfide. It has been established that hypercapnia enhanced the ozone effect on the blood oxygen transport function and was characterized by the oxyhemoglobin dissociation curve shift to the right, also increased hydrogen sulfide synthesis and absence of changes in the nitrates/nitrites concentration. Under these conditions nitroglycerin and sodium hydrosulfide did not change the parameters of the blood gas transport function, but increased the level of nitrate/nitrite and hydrogen sulfide. Preliminary hypercapnia does not eliminate the activating effect of ozone on the free radical oxidation processes, and the addition of the applied gaseous transmitter donors does not contribute to the regulation of the studied parameters.


Assuntos
Sulfeto de Hidrogênio , Ozônio , Humanos , Sulfeto de Hidrogênio/farmacologia , Hipercapnia , Nitroglicerina , Oxigênio , Ozônio/farmacologia
17.
J Cardiothorac Surg ; 17(1): 100, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35505367

RESUMO

BACKGROUND: The study was aimed to compare the efficacy and safety of different sedation protocols of dexmedetomidine-remifentanil and propofol-remifentanil for percutaneous closure of atrial septal defects (ASD) under transthoracic echocardiography (TTE) guidance. MATERIAL AND METHODS: From March 2020 to January 2021, of 114 patients screened, 59 ASD patients scheduled for percutaneous closure under TTE guidance were randomly allocated into the dexmedetomidine-remifentanil (D-R) group (n = 29) and the propofol-remifentanil (P-R) group (n = 30). The incidence of hemodynamic and respiratory adverse events, arterial blood gas analysis, induction and recovery time, pain score, infusion rate of remifentanil, satisfaction of the surgeon and patient, additional sedatives were collected for analysis and comparison. RESULTS: The induction time was longer in the D-R group than that in the P-R group (17.66 ± 2.65 min vs 11.43 ± 1.48 min; difference, 6.22 min; 95% CI 5.10 to 7.35; P < 0.001). No differences were observed in the 2 groups in terms of the additional sedatives, infusion rate of remifentanil, pain score, recovery time (P > 0.05). There was no difference between the two groups regarding the incidence of cardiovascular adverse events (6 [20.7%] vs 4 [13.3%]; difference, 7.4%; 95% CI - 11.7 to 26.5%; P = 0.506). Respiratory adverse events occurred in 1 patient (3.4%) in the D-R group, and 8 patients (26.7%) in the P-R group (difference, 23.3%; 95% CI 6.2 to 40.5%; P = 0.026). The incidence of hypercapnia was significantly lower in the D-R group (4 [13.8%]) than in the P-R group (13 [43.3%]; difference, 29.5%; 95% CI 7.8 to 51.2%; P = 0.012). CONCLUSIONS: Except for more rapid the induction time and higher the surgeon satisfaction score in the propofol-remifentanil protocol, the efficacy was similar between two sedation protocols. The hemodynamic stability was comparable, the dexmedetomidine-remifentanil protocol had superior airway security due to fewer hypercapnia and respiratory adverse events.


Assuntos
Comunicação Interatrial , Hipnóticos e Sedativos , Protocolos Clínicos , Dexmedetomidina/efeitos adversos , Combinação de Medicamentos , Comunicação Interatrial/cirurgia , Humanos , Hipercapnia/epidemiologia , Hipnóticos e Sedativos/efeitos adversos , Dor , Propofol/efeitos adversos , Remifentanil/efeitos adversos , Resultado do Tratamento
18.
Physiol Rep ; 10(10): e15245, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35581741

RESUMO

Serotonin is an important mediator modulating behavior, metabolism, sleep, control of breathing, and upper airway function, but the role of aging in serotonin-mediated effects has not been previously defined. Our study aimed to examine the effect of brain serotonin deficiency on breathing during sleep and metabolism in younger and older mice. We measured breathing during sleep, hypercapnic ventilatory response (HCVR), CO2 production (VCO2 ), and O2 consumption (VO2 ) in 16-18-week old and 40-44-week old mice with deficiency of tryptophan hydroxylase 2 (Tph2), which regulates serotonin synthesis specifically in neurons, compared to Tph2+/+ mice. As expected, aging decreased VCO2 and VO2 . Tph2 knockout resulted in an increase in both metabolic indexes and no interaction between age and the genotype was observed. During wakefulness, neither age nor genotype had an effect on minute ventilation. The genotype did not affect hypercapnic sensitivity in younger mice. During sleep, Tph2-/- mice showed significant decreases in maximal inspiratory flow in NREM sleep, respiratory rate, and oxyhemoglobin saturation in REM sleep, compared to wildtype, regardless of age. Neither serotonin deficiency nor aging affected the frequency of flow limited breaths (a marker of upper airway closure) or apneas. Serotonin deficiency increased the amount and efficiency of sleep only in older animals. In conclusion, younger Tph2-/- mice were able to defend their ventilation and phenotypically did not differ from wildtype during wakefulness. In contrast, both young and old Tph2-/- mice showed sleep-related hypoventilation, which was manifested by hypoxemia during REM sleep.


Assuntos
Respiração , Serotonina , Animais , Encéfalo/metabolismo , Hipercapnia , Camundongos , Serotonina/metabolismo , Sono REM/fisiologia
19.
Trials ; 23(1): 393, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35551646

RESUMO

BACKGROUND: Home noninvasive positive pressure ventilation (NIPPV) has become evidence-based care for stable hypercapnic chronic obstructive pulmonary disease (COPD) patients. There are still other challenges including appropriate follow-up, telemonitor, and management to ensure treatment effectiveness, compliance, and security and to improve quality of life. The Internet of things (IOT) is the name given to the network of devices and other "things" with built-in sensors, software, electronics, and network connectivity, communicating these objects over wireless networks and sending data to a cloud platform. The study aims to evaluate the effectiveness and safety of the IOT-based management of NIPPV for the COPD patients with hypercapnic chronic respiratory failure. METHODS: This multicenter, prospective, randomized controlled trial was conducted with a total of 200 COPD patients with chronic hypercapnic respiratory failure. Using a computer-generated randomization process, patients were randomized (in a 1:1 ratio) into the usual NIPPV (control group) or to receive additional IOT-based management (intervention group) for 12 months. The primary outcome was the Severe Respiratory Insufficiency (SRI) questionnaire. Secondary outcomes included compliance with the ventilator, gas exchange, lung function, health-related quality of life, hospitalization frequency, time to death within 1-year, all-cause mortality, safety analysis, and cost-effectiveness analysis. DISCUSSION: This study will be the first and largest randomized trial in China to evaluate the effectiveness and safety of the IOT-based management of NIPPV for COPD patients with chronic hypercapnic respiratory failure. The results will help to understand the current situation of IOT-based home ventilation and may provide new evidence for home NIPPV treatment and management in the future. TRIAL REGISTRATION: Chinese Clinical Trials Registry ChiCTR1800019536 . Registered on 17 November 2018.


Assuntos
Internet das Coisas , Ventilação não Invasiva , Doença Pulmonar Obstrutiva Crônica , Insuficiência Respiratória , Humanos , Hipercapnia/diagnóstico , Hipercapnia/terapia , Estudos Multicêntricos como Assunto , Ventilação não Invasiva/efeitos adversos , Ventilação não Invasiva/métodos , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/terapia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia
20.
J Clin Sleep Med ; 18(8): 1909-1919, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35499151

RESUMO

STUDY OBJECTIVES: Patients with obstructive sleep apnea (OSA) have a disproportionate increase in postoperative complications and medical emergency team activation (META). We previously introduced DOISNORE50 (Diseases, Observed apnea, Insomnia, Snoring, Neck circumference > 18 inches, Obesity with BMI > 32, R = are you male, Excessive daytime sleepiness, 50 = age ≥ 50) from sleep questionnaire ISNORED using features associated with increased odds of META in perioperative patients. Performance of DOISNORE50 (DOISNORE) had yet to be tested. METHODS: The performance of DOISNORE was tested along with questionnaire ISNORED and STOP-BANG questionnaires among 300 out of 392 participants without known OSA referred to the sleep lab. In study 2, the performance of DOISNORE was tested among 64,949 lives screened in perioperative assessment clinic from 2016 to 2020. RESULTS: Receiver operating characteristic curve demonstrated that best performance was achieved with responses, with area under curve of 0.801. DOISNORE's predictability of OSA risk remained stable from 2018 to 2020 with area under curve of 0.78 and a Cronbach alpha of 0.65. Patients at high risk for OSA (DOISNORE ≥ 6) were associated with an increase of META (odds ratio 1.30, 95% confidence interval 1.12-1.45). Higher relative risk was noted among patients with congestive heart failure and hypercapnia. CONCLUSIONS: DOISNORE is predictive of OSA and postoperative META. Perioperative strategies against META should consider DOISNORE questionnaire and focused screening among patients with heart failure and hypercapnia. CITATION: Namen AM, Forest D, Saha AK, et al. DOISNORE50: a perioperative sleep questionnaire predictive of obstructive sleep apnea and postoperative medical emergency team activation. A learning health system approach to sleep questionnaire development and screening. J Clin Sleep Med. 2022;18(8):1909-1919.


Assuntos
Sistema de Aprendizagem em Saúde , Apneia Obstrutiva do Sono , Humanos , Hipercapnia , Masculino , Programas de Rastreamento , Polissonografia , Sono , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Inquéritos e Questionários
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