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1.
Nat Commun ; 12(1): 1493, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33674571

RESUMO

Wildfires are becoming more frequent and destructive in a changing climate. Fine particulate matter, PM2.5, in wildfire smoke adversely impacts human health. Recent toxicological studies suggest that wildfire particulate matter may be more toxic than equal doses of ambient PM2.5. Air quality regulations however assume that the toxicity of PM2.5 does not vary across different sources of emission. Assessing whether PM2.5 from wildfires is more or less harmful than PM2.5 from other sources is a pressing public health concern. Here, we isolate the wildfire-specific PM2.5 using a series of statistical approaches and exposure definitions. We found increases in respiratory hospitalizations ranging from 1.3 to up to 10% with a 10 µg m-3 increase in wildfire-specific PM2.5, compared to 0.67 to 1.3% associated with non-wildfire PM2.5. Our conclusions point to the need for air quality policies to consider the variability in PM2.5 impacts on human health according to the sources of emission.


Assuntos
Material Particulado/toxicidade , Respiração/efeitos dos fármacos , Fumaça/análise , Incêndios Florestais , Poluentes Atmosféricos/análise , Poluição do Ar/análise , California , Mudança Climática , Exposição Ambiental , Hospitalização , Humanos , Material Particulado/análise , Saúde Pública , Estações do Ano
2.
Aquat Toxicol ; 233: 105773, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33610857

RESUMO

The 2010 Deepwater Horizon (DWH) crude oil spill, among the largest environmental disasters in U.S. history, affected numerous economically important fishes. Exposure to crude oil can lead to reduced cardiac function, limiting oxygen transport, ATP production, and aerobic performance. However, crude oil exposure is not the only stressor that affects aerobic performance, and increasing environmental temperatures are known to significantly increase metabolic demands in fishes. As the DWH spill was active during warm summer months in the Gulf of Mexico, it is important to understand the combined effects of oil and temperature on a suite of metabolic parameters. Therefore, we investigated the effects of 24h crude oil exposure on the aerobic metabolism and hypoxia tolerance of red drum (Sciaenops ocellatus) following 3 week chronic exposure to four ecologically relevant temperatures (18 °C, 22 °C, 25 °C, 28 °C). Our results show that individuals acclimated to higher temperatures had significantly higher standard metabolic rate than individuals at lower temperatures, which resulted in significantly decreased critical oxygen threshold and reduced recovery from exercise. As predicted, crude oil exposure resulted in lower maximum metabolic rates (MMR) across the temperature range, and a significantly reduced ability to recover from exercise. The lowest temperature acclimation showed the smallest effect of oil on MMR, while the highest temperature showed the smallest effect on exercise recovery. Reduced respiratory performance and hypoxia tolerance are likely to have meaningful impacts on the fitness of red drum, especially with climate-induced temperature increases and continued oil exploration in the Gulf of Mexico.


Assuntos
Perciformes/fisiologia , Poluição por Petróleo/análise , Petróleo/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Respiração/efeitos dos fármacos , Temperatura , Poluentes Químicos da Água/toxicidade , Animais , Metabolismo Energético/efeitos dos fármacos , Golfo do México , Água do Mar/química
3.
Chemosphere ; 263: 128008, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32841879

RESUMO

The anthranilic diamide, chlorantraniliprole is a systemic insecticide affecting ryanodine receptors. This insecticide is used to control caterpillars in soybean crops because it has low toxicity to non-target organisms. The objective was to identify side-effects of chlorantraniliprole on midgut histopathology, respiration and behavior of the velvetbean caterpillar Anticarsia gemmatalis in laboratoty. Chlorantraniliprole has LC50 = 0.61 (0.58-0.64) mg mL-1 for A. gemmatalis fourth instar caterpillars after 96 h. The insecticide causes severe histopathological effects in the midgut with epithelial disorganization, microvilli degeneration, cytoplasm vacuolization, cell fragmentation, and peritrophic matrix disorganization. The respiratory rate and the walking speed decrease, whereas the resting period increase for caterpillars exposed to this insecticide. Chlorantraniliprole is toxic to A. gemmatalis at median lethal concentrations causing severe histological and ultrastructural changes with degeneration of the midgut epithelium, reduction of respiratory rates and inducing an arresting behavioral response of this insect.


Assuntos
Inseticidas/toxicidade , Lepidópteros/fisiologia , ortoaminobenzoatos/toxicidade , Animais , Sistema Digestório , Larva , Locomoção/efeitos dos fármacos , Microvilosidades , Mariposas , Respiração/efeitos dos fármacos , Soja
4.
Anesthesiology ; 133(4): 824-838, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32773689

RESUMO

BACKGROUND: Volatile anesthetics moderately depress respiratory function at clinically relevant concentrations. Phox2b-expressing chemosensitive neurons in the retrotrapezoid nucleus, a respiratory control center, are activated by isoflurane, but the underlying mechanisms remain unclear. The hypothesis of this study was that the sodium leak channel contributes to the volatile anesthetics-induced modulation of retrotrapezoid nucleus neurons and to respiratory output. METHODS: The contribution of sodium leak channels to isoflurane-, sevoflurane-, and propofol-evoked activity of Phox2b-expressing retrotrapezoid nucleus neurons and respiratory output were evaluated in wild-type and genetically modified mice lacking sodium leak channels (both sexes). Patch-clamp recordings were performed in acute brain slices. Whole-body plethysmography was used to measure the respiratory activity. RESULTS: Isoflurane at 0.42 to 0.50 mM (~1.5 minimum alveolar concentration) increased the sodium leak channel-mediated holding currents and conductance from -75.0 ± 12.9 to -130.1 ± 34.9 pA (mean ± SD, P = 0.002, n = 6) and 1.8 ± 0.5 to 3.6 ± 1.0 nS (P = 0.001, n = 6), respectively. At these concentrations, isoflurane increased activity of Phox2b-expressing retrotrapezoid nucleus neurons from 1.1 ± 0.2 to 2.8 ± 0.2 Hz (P < 0.001, n = 5), which was eliminated by bath application of gadolinium or genetic silencing of sodium leak channel. Genetic silencing of sodium leak channel in the retrotrapezoid nucleus resulted in a diminished ventilatory response to carbon dioxide in mice under control conditions and during isoflurane anesthesia. Sevoflurane produced an effect comparable to that of isoflurane, whereas propofol did not activate sodium leak channel-mediated holding conductance. CONCLUSIONS: Isoflurane and sevoflurane increase neuronal excitability of chemosensitive retrotrapezoid nucleus neurons partly by enhancing sodium leak channel conductance. Sodium leak channel expression in the retrotrapezoid nucleus is required for the ventilatory response to carbon dioxide during anesthesia by isoflurane and sevoflurane, thus identifying sodium leak channel as a requisite determinant of respiratory output during anesthesia of volatile anesthetics.


Assuntos
Anestésicos Inalatórios/administração & dosagem , Canais Iônicos/agonistas , Proteínas de Membrana/agonistas , Neurônios/efeitos dos fármacos , Respiração/efeitos dos fármacos , Complexo Olivar Superior/efeitos dos fármacos , Animais , Feminino , Canais Iônicos/fisiologia , Masculino , Proteínas de Membrana/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Técnicas de Cultura de Órgãos , Canais de Sódio/fisiologia , Complexo Olivar Superior/fisiologia
5.
Leg Med (Tokyo) ; 47: 101746, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32717552

RESUMO

The acute toxicity of high concentrations of carbon dioxide (CO2) was investigated in anesthetized rats using physiological parameters. At an oxygen concentration of 21%, the survival time decreased in a concentration-dependent manner from ≥7.3 h at 20% CO2 to 1.0 h at 50% CO2. The animals were divided into groups that were exposed to 40% CO2 and 21% O2 balanced with nitrogen (CO2 group), 40% CO2 and 12.6% O2 (CO2-Hypoxia group), 0% CO2 and 12.6% O2 (Hypoxia group), and 0% CO2 and 21% O2 (Control group) for 3 h. In the CO2 group, mean blood pressure (MBP) increased temporarily in the first 60 min followed by a gradual decrease, while breathing rate (BR) decreased immediately up to 3 h and the concentration of serum indicators reflecting organ damage increased. Most of these effects progressed in the CO2-Hypoxia group. The Hypoxia group showed a contrasting response to the CO2 groups in MBP and BR, and a slight partial increase in the serum indicators. Histological changes were not observed in any primary organs of any group, except for eosinophilic or necrosis of pyramidal cells in the hippocampal CA1 region of the CO2 group. These results indicate that high concentrations of CO2 inhalation are toxic, likely due to BR suppression, and that hypoxia produced under a high CO2 environment, while showing little effect on its own, enhances the toxic effects of CO2.


Assuntos
Dióxido de Carbono/toxicidade , Animais , Pressão Sanguínea/efeitos dos fármacos , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/patologia , Dióxido de Carbono/administração & dosagem , Dióxido de Carbono/efeitos adversos , Relação Dose-Resposta a Droga , Exposição Ambiental/efeitos adversos , Hipóxia/etiologia , Inalação , Masculino , Ratos Wistar , Respiração/efeitos dos fármacos
6.
Am J Respir Cell Mol Biol ; 63(4): 502-509, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32603263

RESUMO

Respiratory depression is the main cause of morbidity and mortality associated with opioids. Obesity increases opioid-related mortality, which is mostly related to comorbid obstructive sleep apnea. Naloxone, a µ-opioid receptor blocker, is an effective antidote, but it reverses analgesia. Like humans with obesity, mice with diet-induced obesity hypoventilate during sleep and develop obstructive sleep apnea, which can be treated with intranasal leptin. We hypothesized that intranasal leptin reverses opioid-induced sleep-disordered breathing in obese mice without decreasing analgesia. To test this hypothesis, mice with diet-induced obesity were treated with morphine at 10 mg/kg subcutaneously and with leptin or placebo intranasally. Sleep and breathing were recorded by barometric plethysmography, and pain sensitivity was measured by the tail-flick test. Excitatory postsynaptic currents were recorded in vitro from hypoglossal motor neurons after the application of the µ-opioid receptor agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin and leptin. Morphine dramatically increased the frequency of apneas and greatly increased the severity of hypoventilation and obstructive sleep apnea. Leptin decreased the frequency of apneas, improved obstructive sleep apnea, and completely reversed hypoventilation, whereas morphine analgesia was enhanced. Our in vitro studies demonstrated that [D-Ala2, N-MePhe4, Gly-ol]-enkephalin reduced the frequency of excitatory postsynaptic currents in hypoglossal motoneurons and that application of leptin restored excitatory synaptic neurotransmission. Our findings suggest that intranasal leptin may prevent opioid respiratory depression during sleep in patients with obesity receiving opioids without reducing analgesia.


Assuntos
Analgésicos Opioides/efeitos adversos , Leptina/administração & dosagem , Respiração/efeitos dos fármacos , Síndromes da Apneia do Sono/induzido quimicamente , Síndromes da Apneia do Sono/prevenção & controle , Sono/efeitos dos fármacos , Administração Intranasal/métodos , Analgesia/métodos , Animais , Modelos Animais de Doenças , Encefalinas/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Morfina/farmacologia , Neurônios Motores/efeitos dos fármacos , Neurônios Motores/metabolismo , Receptores Opioides mu/metabolismo , Síndromes da Apneia do Sono/metabolismo , Transmissão Sináptica/efeitos dos fármacos
7.
Pediatrics ; 146(2)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32680879

RESUMO

OBJECTIVES: Cardiorespiratory and pulse oximetry monitoring in children who are hospitalized should balance benefits of detecting deterioration with potential harms of alarm fatigue. We developed recommendations for monitoring outside the ICU on the basis of available evidence and expert opinion. METHODS: We conducted a comprehensive literature search for studies addressing the utility of cardiorespiratory and pulse oximetry monitoring in common pediatric conditions and drafted candidate monitoring recommendations based on our findings. We convened a panel of nominees from national professional organizations with diverse expertise: nursing, medicine, respiratory therapy, biomedical engineering, and family advocacy. Using the RAND/University of California, Los Angeles Appropriateness Method, panelists rated recommendations for appropriateness and necessity in 3 sequential rating sessions and a moderated meeting. RESULTS: The panel evaluated 56 recommendations for intermittent and continuous monitoring for children hospitalized outside the ICU with 7 common conditions (eg, asthma, croup) and/or receiving common therapies (eg, supplemental oxygen, intravenous opioids). The panel reached agreement on the appropriateness of monitoring recommendations for 55 of 56 indications and on necessity of monitoring for 52. For mild or moderate asthma, croup, pneumonia, and bronchiolitis, the panel recommended intermittent vital sign or oximetry measurement only. The panel recommended continuous monitoring for severe disease in each respiratory condition as well as for a new or increased dose of intravenous opiate or benzodiazepine. CONCLUSIONS: Expert panel members agreed that intermittent vital sign assessment, rather than continuous monitoring, is appropriate management for a set of specific conditions of mild or moderate severity that require hospitalization.


Assuntos
Eletrocardiografia , Monitorização Fisiológica/métodos , Oximetria , Guias de Prática Clínica como Assunto , Transtornos Respiratórios/fisiopatologia , Testes de Função Respiratória , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/farmacologia , Benzodiazepinas/efeitos adversos , Benzodiazepinas/farmacologia , Criança , Criança Hospitalizada , Técnica Delfos , Relação Dose-Resposta a Droga , Humanos , Oxigenoterapia , Respiração/efeitos dos fármacos , Transtornos Respiratórios/etiologia , Sepse/fisiopatologia
8.
Am J Physiol Regul Integr Comp Physiol ; 319(2): R233-R242, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32579854

RESUMO

Continuous infusion of prostaglandin E1 (PGE1) is used to maintain ductus arteriosus patency in infants with critical congenital heart disease, but it can also cause central apnea suggesting an effect on respiratory neural control. In this study, we investigated whether 1) PGE1 inhibits the various phases of the acute hypoxic ventilatory response (HVR; an index of respiratory control dysfunction) and increases apnea incidence in neonatal rats; and 2) whether these changes would be reversible with caffeine pretreatment. Whole body plethysmography was used to assess the HVR and apnea incidence in neonatal rats 2 h following a single bolus intraperitoneal injection of PGE1 with and without prior caffeine treatment. Untreated rats exhibited a biphasic HVR characterized by an initial increase in minute ventilation followed by a ventilatory decline of the late phase (~5th minute) of the HVR. PGE1 had a dose-dependent effect on the HVR. Contrary to our hypothesis, the lowest dose (1 µg/kg) of PGE1 prevented the ventilatory decline of the late phase of the HVR. However, PGE1 tended to increase postsigh apnea incidence and the coefficient of variability (CV) of breathing frequency, suggesting increased respiratory instability. PGE1 also decreased brainstem microglia mRNA and increased neuronal nitric oxide synthase (nNOS) and platelet-derived growth factor-ß (PDGF-ß) gene expression. Caffeine pretreatment prevented these effects of PGE1, and the adenosine A2A receptor inhibitor MSX-3 had similar preventative effects. Prostaglandin appears to have deleterious effects on brainstem respiratory control regions, possibly involving a microglial-dependent mechanism. The compensatory effects of caffeine or MSX-3 treatment raises the question of whether prostaglandin may also operate on an adenosine-dependent pathway.


Assuntos
Alprostadil/farmacologia , Tronco Encefálico/efeitos dos fármacos , Cafeína/farmacologia , Ventilação Pulmonar/efeitos dos fármacos , Respiração/efeitos dos fármacos , Animais , Tronco Encefálico/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Óxido Nítrico Sintase Tipo I/metabolismo , Pletismografia Total , Proteínas Proto-Oncogênicas c-sis/genética , Proteínas Proto-Oncogênicas c-sis/metabolismo , Antagonistas de Receptores Purinérgicos P1/farmacologia , Ratos , Ratos Sprague-Dawley
9.
Encephale ; 46(3S): S93-S98, 2020 Jun.
Artigo em Francês | MEDLINE | ID: mdl-32507556

RESUMO

Although the "panic" word has been abundantly linked to the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic in the press, in the scientific literature very few studies have considered whether the current epidemic could predispose to the onset or the aggravation of panic attacks or panic disorder. Indeed, most studies thus far have focused on the risk of increase and aggravation of other psychiatric disorders as a consequence of the SARS-CoV-2 epidemic, such as obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and generalized anxiety disorder (GAD). Yet, risk of onset or aggravation of panic disorder, especially the subtype with prominent respiratory symptoms, which is characterized by a fear response conditioning to interoceptive sensations (e.g., respiratory), and hypervigilance to these interoceptive signals, could be expected in the current situation. Indeed, respiratory symptoms, such as coughs and dyspnea, are among the most commonly associated with the SARS-CoV-2 (59-82% and 31-55%, respectively), and respiratory symptoms are associated with a poor illness prognosis. Hence given that some etiological and maintenance factors associated with panic disorder - i.e., fear conditioning to abnormal breathing patterns attributable or not to the COVID-19 (coronavirus disease 2019), as well as hypervigilance towards breathing abnormalities - are supposedly more prevalent, one could expect an increased risk of panic disorder onset or aggravation following the COVID-19 epidemic in people who were affected by the virus, but also those who were not. In people with the comorbidity (i.e., panic disorder or panic attacks and the COVID-19), it is particularly important to be aware of the risk of hypokalemia in specific at-risk situations or prescriptions. For instance, in the case of salbutamol prescription, which might be overly used in patients with anxiety disorders and COVID-19, or in patients presenting with diarrhea and vomiting. Hypokalemia is associated with an increased risk of torsade de pointe, thus caution is required when prescribing specific psychotropic drugs, such as the antidepressants citalopram and escitalopram, which are first-line treatments for panic disorder, but also hydroxyzine, aiming at anxiety reduction. The results reviewed here highlight the importance of considering and further investigating the impact of the current pandemic on the diagnosis and treatment of panic disorder (alone or comorbid with the COVID-19).


Assuntos
Betacoronavirus , Infecções por Coronavirus/psicologia , Pandemias , Transtorno de Pânico/psicologia , Pneumonia Viral/psicologia , Ansiedade/etiologia , Ansiedade/psicologia , Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/fisiopatologia , Transtornos de Ansiedade/psicologia , Catastrofização , Comorbidade , Infecções por Coronavirus/epidemiologia , Dispneia/etiologia , Dispneia/psicologia , Feminino , Humanos , Hipopotassemia/etiologia , Masculino , Transtorno de Pânico/tratamento farmacológico , Transtorno de Pânico/epidemiologia , Transtorno de Pânico/fisiopatologia , Pneumonia Viral/epidemiologia , Psicotrópicos/efeitos adversos , Psicotrópicos/uso terapêutico , Sistema Renina-Angiotensina/fisiologia , Respiração/efeitos dos fármacos , Estresse Psicológico/etiologia , Estresse Psicológico/fisiopatologia , Terminologia como Assunto , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/etiologia
10.
Cardiovasc Drugs Ther ; 34(5): 685-688, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32488425

RESUMO

PURPOSE: Left ventricular outflow tract obstruction (LVOTO) is a relatively uncommon but severe condition that may lead to hemodynamic impairment. It can be elicited by morphological (left ventricular hypertrophy, sigmoid septum, prominent papillary muscle, prolonged anterior mitral valve leaflet) and functional (hypovolemia, low afterload, hypercontractility, catecholamines) factors. We sought to determine the incidence of the most severe form of LVOTO in septic shock patients and describe the therapeutic effects of vasopressin. METHODS: Over a period of 29 months, 527 patients in septic shock were screened for LVOTO. All were mechanically ventilated and treated according to sepsis bundles, including pre-load optimization and norepinephrine infusion. Vasopressin was added in addition to norepinephrine to reduce the adrenergic burden and decrease LVOTO. RESULTS: Ten patients were diagnosed with the most severe form of LVOTO, including systolic anterior mitral valve motion (SAM) and severe mitral regurgitation (MR) with pulmonary oedema. The median norepinephrine dosage to obtain a mean arterial pressure of ≥70 mmHg was 0.58 mcg/Kg/min (IQR 0.40-0.78). All patients had a hyper-contractile left ventricle, septal hypertrophy, significant LVOTO (peak gradient 78 [56-123] mmHg) associated with SAM and severe MR with pulmonary oedema. Vasopressin (median 4 IU/h) allowed a significant reduction of norepinephrine (0.18 [0.14-0.30] mcg/kg/min; p = 0.01), LVOT gradient (35 [24-60] mmHg; p = 0.01) and MR with a significant paO2/FiO2 increase (174 [125-213] mmHg; p = 0.01). CONCLUSION: Vasopressin allowed a reduction of norepinephrine with subsequent LVOTO reduction and hemodynamic improvement of the most severe form of LVOTO, which represented 1.9% of all septic shock patients.


Assuntos
Arginina Vasopressina/uso terapêutico , Hemodinâmica/efeitos dos fármacos , Choque Séptico/tratamento farmacológico , Vasoconstritores/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos , Obstrução do Fluxo Ventricular Externo/tratamento farmacológico , Agonistas Adrenérgicos/uso terapêutico , Idoso , República Tcheca/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Norepinefrina/uso terapêutico , Recuperação de Função Fisiológica , Respiração/efeitos dos fármacos , Índice de Gravidade de Doença , Choque Séptico/diagnóstico por imagem , Choque Séptico/epidemiologia , Choque Séptico/fisiopatologia , Resultado do Tratamento , Obstrução do Fluxo Ventricular Externo/diagnóstico por imagem , Obstrução do Fluxo Ventricular Externo/epidemiologia , Obstrução do Fluxo Ventricular Externo/fisiopatologia
11.
PLoS One ; 15(6): e0234193, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555612

RESUMO

Lung volume is modulated by sensory afferent feedback via vagal and spinal pathways. The purpose of this study was to systematically alter afferent feedback with and without a mechanical challenge (chest compression). We hypothesized that manipulation of afferent feedback by nebulization of lidocaine, extra-thoracic vagotomy, or lidocaine administration to the pleural space would produce differential effects on the motor pattern of breathing during chest compression in sodium pentobarbital anesthetized rats (N = 43). Our results suggest that: 1) pulmonary stretch receptors are not the sole contributor to breathing feedback in adult male and female rats; 2) of our manipulations, chest compression had the largest effect on early expiratory diaphragm activity ("yield"); 3) reduction of spinally-mediated afferent feedback modulates breathing patterns most likely via inhibition; and 4) breathing parameters demonstrate large sex differences. Compared to males, female animals had lower respiratory rates (RR), which were further depressed by vagotomy, while chest compression increased RR in males, and decreased yield in females without changing RR. Collectively, our results suggest that balance between tonic vagal inhibition and spinal afferent feedback maintains breathing characteristics, and that it is important to specifically evaluate sex differences when studying control of breathing.


Assuntos
Respiração , Vias Aferentes , Animais , Reanimação Cardiopulmonar , Feminino , Lidocaína/administração & dosagem , Lidocaína/farmacologia , Masculino , Nebulizadores e Vaporizadores , Ratos Sprague-Dawley , Respiração/efeitos dos fármacos , Fatores Sexuais , Vagotomia , Nervo Vago/fisiologia , Nervo Vago/cirurgia
12.
Encephale ; 46(3S): S116-S118, 2020 Jun.
Artigo em Francês | MEDLINE | ID: mdl-32360037
13.
Life Sci ; 249: 117472, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32112870

RESUMO

Aim Determine changes in the expressions of the ion channel-TRPV1-and neuropeptides-NKA, NKB, calcitonin gene-related peptide (CGRP), and SP-in 14-, 21-, and 42-day-old rats after inhaling 1.5% and 2.6% sevoflurane. MAIN METHODS: A small in-house inhalation anesthesia chamber was designed to allow 14-, 21-, and 42-day-old rats inhale 1.5% and 2.6% sevoflurane, and rats in the control group inhaled carrier gas(1 L/min air +1 L/min O2). In addition, 14- and 21-day-old rats were pretreated with capsazepine, followed by inhalation of 1.5% and 2.6% sevoflurane or the carrier gas. The expression of TRPV1 in lung tissues was detected by Western blotting, whereas the expressions of NKA, NKB, CGRP, and SP in the trachea were detected by immunohistochemistry. KEY FINDINGS: After inhalation of 1.5% sevoflurane, the expression of TRPV1 in the lung tissues of 14- and 21-day-old rats was significantly increased compared with that in the control group, which was antagonized by capsazepine pretreatment. Moreover, inhalation of 1.5% sevoflurane markedly increased the expressions of NKA, NKB, CGRP, and SP in the trachea of 21-day-old rats and of NKB, CGRP, and SP in the trachea of 14-day-old rats. The expressions of these molecules were antagonized by capsazepine pretreatment. Conversely, inhalation of 2.6% sevoflurane decreased the expressions of NKA and NKB in the trachea of 42-day-old rats. SIGNIFICANCE: Sevoflurane did not upregulate the expression of TRPV1 in the airways of late-developing rats. This anesthetic may have a two-way effect on airways, resulting in considerable effects in pediatric clinical anesthesia management.


Assuntos
Anestésicos Inalatórios/administração & dosagem , Sevoflurano/administração & dosagem , Canais de Cátion TRPV/metabolismo , Traqueia/metabolismo , Administração por Inalação , Fatores Etários , Animais , Gasometria , Peso Corporal/efeitos dos fármacos , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Capsaicina/análogos & derivados , Capsaicina/farmacologia , Relação Dose-Resposta a Droga , Neurocinina A/metabolismo , Neurocinina B/metabolismo , Ratos , Ratos Sprague-Dawley , Respiração/efeitos dos fármacos , Substância P/metabolismo
14.
Acta Vet Scand ; 62(1): 14, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164761

RESUMO

BACKGROUND: General anaesthesia in pigs maintained with intravenous drugs such as propofol may cause respiratory depression. Alfaxalone gives less respiratory depression than propofol in some species. The aim of the investigation was to compare respiratory effects of propofol-ketamine-dexmedetomidine and alfaxalone-ketamine-dexmedetomidine in pigs. Sixteen pigs premedicated with ketamine 15 mg/kg and midazolam 1 mg/kg intramuscularly were anaesthetised with propofol or alfaxalone to allow endotracheal intubation, followed by propofol 8 mg/kg/h or alfaxalone 5 mg/kg/h in combination with ketamine 5 mg/kg/h and dexmedetomidine 4 µg/kg/h given as a continuous infusion for 60 min. The pigs breathed spontaneously with an FIO2 of 0.21. Oxygen saturation (SpO2), end-tidal CO2 concentration (PE'CO2), respiratory rate (fR) and inspired tidal volume (VT) were measured, and statistically compared between treatments. If the SpO2 dropped below 80% or if PE'CO2 increased above 10.0 kPa, the pigs were recorded as failing to complete the study, and time to failure was statistically compared between treatments. RESULTS: Alfaxalone treated pigs had significantly higher respiratory rates and lower PE'CO2 than propofol treated pigs, with a fR being 7.3 /min higher (P = 0.01) and PE'CO2 0.8 kPa lower (P = 0.05). SpO2 decreased by 0.6% and fR by 1.0 /min per kg increase in body weight in both treatment groups. Three of eight propofol treated and two of eight alfaxalone treated pigs failed to complete the study, and times to failure were not significantly different between treatments (P = 0.75). CONCLUSIONS: No major differences in respiratory variables were found when comparing treatments. Respiratory supportive measures must be available when using both protocols.


Assuntos
Anestesia Geral/métodos , Anestésicos Gerais , Respiração/efeitos dos fármacos , Anestésicos Gerais/administração & dosagem , Anestésicos Gerais/farmacologia , Animais , Dexmedetomidina/administração & dosagem , Dexmedetomidina/farmacologia , Quimioterapia Combinada , Feminino , Ketamina/administração & dosagem , Ketamina/farmacologia , Masculino , Pregnanodionas/administração & dosagem , Pregnanodionas/farmacologia , Propofol/administração & dosagem , Propofol/farmacologia , Taxa Respiratória/efeitos dos fármacos , Suínos
16.
Biomolecules ; 10(2)2020 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-31991782

RESUMO

: GAL-021 has recently been developed as a novel breathing control modulator. However, modifications of ionic currents produced by this agent remain uncertain, although its efficacy in suppressing the activity of big-conductance Ca2+-activated K+ (BKCa) channels has been reported. In pituitary tumor (GH3) cells, we found that the presence of GAL-021 decreased the amplitude of macroscopic Ca2+-activated K+ current (IK(Ca)) in a concentration-dependent manner with an effective IC50 of 2.33 µM. GAL-021-mediated reduction of IK(Ca) was reversed by subsequent application of verteporfin or ionomycin; however, it was not by that of diazoxide. In inside-out current recordings, the addition of GAL-021 to the bath markedly decreased the open-state probability of BKCa channels. This agent also resulted in a rightward shift in voltage dependence of the activation curve of BKCa channels; however, neither the gating charge of the curve nor single-channel conductance of the channel was changed. There was an evident lengthening of the mean closed time of BKCa channels in the presence of GAL-021, with no change in mean open time. The GAL-021 addition also suppressed M-type K+ current with an effective IC50 of 3.75 µM; however, its presence did not alter the amplitude of erg-mediated K+ current, or mildly suppressed delayed-rectifier K+ current. GAL-021 at a concentration of 30 µM could also suppress hyperpolarization-activated cationic current. In HEK293T cells expressing α-hSlo, the addition of GAL-021 was also able to suppress the BKCa-channel open probabilities, and GAL-021-mediated suppression of BKCa-channel activity was attenuated by further addition of BMS-191011. Collectively, the GAL-021 effects presented herein do not exclusively act on BKCa channels and these modifications on ionic currents exert significant influence on the functional activities of electrically excitable cells occurring in vivo.


Assuntos
Neoplasias Hipofisárias/tratamento farmacológico , Respiração/efeitos dos fármacos , Triazinas/farmacologia , Cálcio/metabolismo , Diazóxido/farmacologia , Células HEK293 , Humanos , Ionomicina/farmacologia , Neoplasias Hipofisárias/patologia , Verteporfina/farmacologia
18.
J Vet Med Sci ; 82(1): 35-42, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31748444

RESUMO

Recently, a mixture of medetomidine, midazolam and butorphanol (MMB) has been used as an injectable general anesthetic agent for laboratory animals. The purpose of this study was to establish data to encourage practical usage of MMB, and to clarify the effects of MMB on the respiratory function in rats. To compare the anesthetic efficacy between the injection routes, the anesthetic effects of MMB by subcutaneous (s.c.) or intraperitoneal (i.p.) injection were evaluated in rats. To assess the respiratory function, the blood gas parameters and electrolytes were assessed in serial venous blood samples collected from before s.c. injection of MMB to 270 min after the injection. Recovery from anesthesia and the respiratory changes after atipamezole injection at 30 min after MMB injection was also examined. Subcutaneous injection of MMB was associated with more rapid induction and a longer duration of anesthesia as compared to i.p. injection. The blood gas analysis findings showed MMB had effects on respiratory function, that is, elevations of the partial pressures of carbon dioxide and bicarbonate and reduction of the blood pH. Atipamezole injection resulted in recovery from the MMB-induced anesthetic effect as well as respiratory depression. In conclusion, MMB provides more effective anesthesia administered by s.c. injection compared to i.p. injection and induces respiratory change. These changes were counteracted by atipamezole. Therefore, we recommend MMB administered by s.c. injection for anesthesia, followed by injection of atipamezole after the operative procedure to allow recovery.


Assuntos
Anestésicos Combinados/administração & dosagem , Butorfanol/administração & dosagem , Medetomidina/administração & dosagem , Midazolam/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Analgésicos Opioides/administração & dosagem , Anestesia/veterinária , Animais , Gasometria , Hipnóticos e Sedativos/administração & dosagem , Imidazóis/administração & dosagem , Injeções Intraperitoneais , Injeções Subcutâneas , Masculino , Ratos Sprague-Dawley , Respiração/efeitos dos fármacos
19.
Am J Physiol Lung Cell Mol Physiol ; 318(1): L41-L48, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31617728

RESUMO

Mechanical ventilation from birth with normal tidal volumes (VT) causes lung injury and systemic responses in preterm sheep. The addition of budesonide to surfactant therapy decreases these injury markers. Budesonide and surfactant will decrease the injury from injurious VT ventilation in preterm sheep. Lambs at 126 ± 1 day gestational age were ventilated from birth with either: 1) Normal VT [surfactant 200 mg/kg before ventilation, positive end expiratory pressure (PEEP) 5 cmH2O, VT 8 mL/kg] or 2) Injury VT (high pressure, 100% oxygen, no PEEP) for 15 min, then further randomized to surfactant + saline or surfactant + 0.25 mg/kg budesonide with Normal VT for 6 h. Lung function and lung, liver, and brain tissues were evaluated for indicators of injury. Injury VT + saline caused significant injury and systemic responses, and Injury VT + budesonide improved lung physiology. Budesonide decreased lung inflammation and decreased pro-inflammatory cytokine mRNA in the lung, liver, and brain to levels similar to Normal VT + saline. Budesonide was present in plasma within 15 min of treatment in both ventilation groups, and less than 5% of the budesonide remained in the lung at 6 h. mRNA sequencing of liver and periventricular white matter demonstrated multiple pathways altered by both Injury VT and budesonide and the combination exposure. In lambs receiving Injury VT, the addition of budesonide to surfactant improved lung physiology and decreased pro-inflammatory cytokine responses in the lung, liver, and brain to levels similar to lambs receiving Normal VT.


Assuntos
Budesonida/farmacologia , Lesão Pulmonar/tratamento farmacológico , Pulmão/efeitos dos fármacos , Surfactantes Pulmonares/farmacologia , Respiração Artificial/efeitos adversos , Animais , Animais Recém-Nascidos/metabolismo , Citocinas/metabolismo , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Fígado/efeitos dos fármacos , Fígado/metabolismo , Pulmão/metabolismo , Lesão Pulmonar/metabolismo , Pneumonia/tratamento farmacológico , Pneumonia/metabolismo , Respiração com Pressão Positiva/métodos , Gravidez , Nascimento Prematuro/metabolismo , RNA Mensageiro/metabolismo , Respiração/efeitos dos fármacos , Ovinos , Volume de Ventilação Pulmonar/efeitos dos fármacos
20.
J Sleep Res ; 29(2): e12930, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31633865

RESUMO

Opioid-related deaths from respiratory depression are increasing but there is only limited information on the effect of morphine on breathing during sleep. This study aimed to detect and quantify opioid-induced cardiorespiratory pattern changes during sleep in obstructive sleep apnea (OSA) patients using novel automated methods and correlate these with conventional polysomnography (PSG) measures. Under a randomized double-blind placebo-controlled crossover design, 60 male OSA patients attended two one-night visits to the sleep laboratory, at least a week apart. Either a 40-mg controlled-release oral morphine dose or placebo was administered. Breathing during sleep was measured by standard in-laboratory PSG. We analysed the inter-breath interval (IBI) from the PSG flow channel to quantify breathing irregularity. Cardiopulmonary coupling (CPC) was analysed using the PSG electrocardiogram (ECG) channel. Following the consumption of morphine, the 60 OSA patients had fewer breaths (p = .0006), a longer inter-breath interval (p < .0001) and more irregular breathing with increased IBI coefficient of variation (CV) (p = .0015) compared to the placebo night. A higher CPC sleep quality index was found with morphine use. The change of key IBI and CPC parameters was significantly correlated with the change of key PSG sleep-disordered breathing parameters. In conclusion, 40 mg controlled-release morphine resulted in a longer breathing cycle and increased breathing irregularity but generally more stable sleep in OSA patients. The significant links between the IBI and CPC techniques and a range of PSG sleep-disordered breathing parameters may suggest a practical value as surrogate overnight cardiorespiratory measurements, because both respiratory flow and ECG can be detected by small portable devices.


Assuntos
Analgésicos Opioides/efeitos adversos , Morfina/efeitos adversos , Polissonografia/métodos , Respiração/efeitos dos fármacos , Apneia Obstrutiva do Sono/fisiopatologia , Adolescente , Adulto , Idoso , Analgésicos Opioides/farmacologia , Estudos Cross-Over , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Morfina/farmacologia , Sono/efeitos dos fármacos , Adulto Jovem
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