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1.
Toxicol Lett ; 316: 127-135, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31539569

RESUMO

Carfentanil (CRF) is an extremely potent opioid capable of inducing fatal respiratory depression. Naloxone (NX) and naltrexone (NTX) are opioid antagonists for which the efficacy against CRF remains largely unexplored. In this study, the effects of aerosolized CRF on respiratory function were investigated using adult male CD-1 mice. Mice were exposed to 0.4 mg/m3 of CRF for 15 min using custom whole-body plethysmograph units. Minute volume (MV), respiratory frequency (f), duty cycle (DC), and tidal volume (TV) were monitored and compared to control animals exposed to aerosolized H2O. CRF exposure induced respiratory depression, characterized by a marked decrease in MV, which was sustained throughout 24 h post-exposure. Prophylactic and therapeutic treatment with intramuscular (i.m.) NX marginally improved MV, with slight dose-dependent effects. Analogous treatment with i.m. NTX returned MV to baseline levels, with all doses and intervention times performing similarly. Despite improvements in MV, treatment administration did not reverse changes in DC, a measure of respiratory timing. Overall, NX and NTX administration alleviated volumetric aspects of opioid-induced respiratory toxicity, while changes in respiratory timing remained unresolved throughout post-exposure observation. These sustained changes and differences in recovery between two aspects of respiratory dynamics may provide insights for further exploration into the underlying mechanism of action of opioids and opioid antagonists.


Assuntos
Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/toxicidade , Fentanila/análogos & derivados , Pulmão/efeitos dos fármacos , Naloxona/administração & dosagem , Naltrexona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Respiração/efeitos dos fármacos , Insuficiência Respiratória/prevenção & controle , Administração por Inalação , Aerossóis , Analgésicos Opioides/farmacocinética , Animais , Simulação por Computador , Relação Dose-Resposta a Droga , Fentanila/administração & dosagem , Fentanila/farmacocinética , Fentanila/toxicidade , Humanos , Pulmão/fisiopatologia , Masculino , Camundongos , Modelos Biológicos , Pletismografia Total , Insuficiência Respiratória/induzido quimicamente , Insuficiência Respiratória/fisiopatologia , Medição de Risco
2.
Toxicol Lett ; 316: 94-108, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499141

RESUMO

The toxic effects resulting from inhalation exposure depend on both the concentration (C) of the inhaled substance and the exposure duration (t), including the assumptions that the exposure-limiting toxic effect is linearly linked with the accumulated C × t (inhaled dose), and detoxification or compensatory responses diminishing this dose are negligible. This interrelationship applies for both constant and fluctuating concentrations and is usually expressed by the toxic load equation Cn × t = constant effect (k). The toxic load exponent 'n' is derived from both C- and t-dependent exponents with Cb2×tb3 = k with n = b2/b3. This model is taken as a fundamental basis for assessing the acute hazard posed by atmospheric releases of noxious substances, whether deliberate or accidental. Despite its universal use, especially for inhaled irritants, the toxicological significance of this mathematical construct is still discussed controversially. With n = 1 this equation is called Haber's rule. The underlying assumption is that the exposure-based calculated and the actually inhaled Cb2×tb3 are identical. Unlike the calculated dose, the latter is dependent on the test species and its t-dependent change in respiratory minute volume (MV). The retention patterns of inhaled irritant vapors may differ in obligate nasal breathing rodents and oronasally breathing humans as well. Thus, due to the interdependence of n on both C, t and k, this mathematical construct generates a bioassay-specific 'n' which can hardly be considered as human-equivalent, especially following exposure to sensory irritants known to elicit reflex-related changes in MV. The C- and t-dependent impact on Cn × t = k was analyzed with the sensory irritant n-butyl monoisocyanate and compared with t-dependent changes elicited by highly, moderately, and poorly water-soluble sensory irritants ammonia, toluene diisocyanate, and phosgene, respectively. This comparison reveals that n depends on several factors: In cases where MV is instantly and plateau-like depressed with onset of exposure, n appears to be most dependent on Cb2 × MV whereas for a similar slower time-dependent response n becomes more dependent on MV × tb3. For any ensuing risk characterization that focuses on acute non-lethal threshold Cb2 × tb3's, the sensory irritation-related depression in MV must be known to arrive at meaningful conclusions. In summary, both Cn- and t-dependent dosimetry-related pitfalls may occur in acute bioassays on rodents following inhalation exposure to irritants. These must be identified and dealt with judiciously prior to translation to apparently similar human exposures. By default, extrapolations from one duration to another should start with that Cn × t eliciting the least depression in MV with n = 1.


Assuntos
Exposição por Inalação/efeitos adversos , Irritantes/toxicidade , Pneumopatias/induzido quimicamente , Pulmão/efeitos dos fármacos , Modelos Teóricos , Respiração/efeitos dos fármacos , Limiar Sensorial/efeitos dos fármacos , Amônia/química , Amônia/toxicidade , Animais , Relação Dose-Resposta a Droga , Irritantes/química , Isocianatos/química , Isocianatos/toxicidade , Dose Letal Mediana , Pulmão/fisiopatologia , Pneumopatias/fisiopatologia , Masculino , Camundongos , Fosgênio/química , Fosgênio/toxicidade , Ratos Wistar , Medição de Risco , Solubilidade , Fatores de Tempo , Tolueno 2,4-Di-Isocianato/química , Tolueno 2,4-Di-Isocianato/toxicidade
3.
Eur J Pharm Biopharm ; 144: 11-17, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499161

RESUMO

With rapid advances in micro-fabrication processes and the availability of biologically-relevant lung cells, the development of lung-on-chip platforms is offering novel avenues for more realistic inhalation assays in pharmaceutical research, and thereby an opportunity to depart from traditional in vitro lung assays. As advanced models capturing the cellular pulmonary make-up at an air-liquid interface (ALI), lung-on-chips emulate both morphological features and biological functionality of the airway barrier with the ability to integrate respiratory breathing motions and ensuing tissue strains. Such in vitro systems allow importantly to mimic more realistic physiological respiratory flow conditions, with the opportunity to integrate physically-relevant transport determinants of aerosol inhalation therapy, i.e. recapitulating the pathway from airborne flight to deposition on the airway lumen. In this short opinion, we discuss such points and describe how these attributes are paving new avenues for exploring improved drug carrier designs (e.g. shape, size, etc.) and targeting strategies (e.g. conductive vs. respiratory regions) amongst other. We argue that while technical challenges still lie along the way in rendering in vitro lung-on-chip platforms more widespread across the general pharmaceutical research community, significant momentum is steadily underway in accelerating the prospect of establishing these as in vitro "gold standards".


Assuntos
Aerossóis/metabolismo , Bioensaio/métodos , Pulmão/metabolismo , Administração por Inalação , Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Humanos , Modelos Biológicos , Tamanho da Partícula , Respiração/efeitos dos fármacos , Terapia Respiratória/métodos
4.
Neurología (Barc., Ed. impr.) ; 34(7): 461-468, sept. 2019. graf
Artigo em Espanhol | IBECS | ID: ibc-186348

RESUMO

Introducción: En los mamíferos, el complejo pre-Bötzinger (preBötC) es una red neuronal bilateral y simétrica localizada en el tallo cerebral, la cual es indispensable para la generación y modulación del ritmo respiratorio. En humanos existen pocos estudios acerca del preBötC y su relación con enfermedades neurológicas no ha sido descrita. Sin embargo, la importancia del preBötC en el control neural del ritmo respiratorio y su posible participación en enfermedades neurológicas en humanos ha sido mostrada gracias a la manipulación farmacológica y de lesiones del preBötC realizadas en modelos animales in vivo e in vitro. Método: En esta revisión describimos los efectos de algunos fármacos sobre la actividad inspiratoria in vitro en el modelo de rebanada transversal del tallo cerebral que contiene el preBötC, y algunos experimentos in vivo. La farmacología fue clasificada de acuerdo con los principales sistemas de neurotransmisión y con la importancia de los fármacos como estimuladores o inhibidores de la actividad del preBötC y, por tanto, de la generación del ritmo respiratorio. Conclusiones: El neurólogo clínico encontrará esta información relevante para entender cómo el sistema nervioso central genera el ritmo respiratorio y, además, podrá relacionarla con las observaciones hechas durante su práctica


Introduction: In mammals, the preBötzinger complex (preBötC) is a bilateral and symmetrical neural network located in the brainstem which is essential for the generation and modulation of respiratory rhythm. There are few human studies about the preBötC and, its relationship with neurological diseases has not been described. However, the importance of the preBötC in neural control of breathing and its potential participation in neurological diseases in humans, has been suggested based on pharmacological manipulation and lesion of the preBötC in animal models, both in vivo and in vitro. Method: In this review, we describe the effects of some drugs on the inspiratory activity in vitro in a transverse slice that contains the preBötC, as well as some in vivo experiments. Drugs were classified according to their effects on the main neurotransmitter systems and their importance as stimulators or inhibitors of preBötC activity and therefore for the generation of the respiratory rhythm. Conclusion: Clinical neurologists will find this information relevant to understanding how the central nervous system generates the respiratory rhythm and may also relate this information to the findings made in daily practice


Assuntos
Humanos , Animais , Tronco Encefálico/fisiologia , Rede Nervosa/fisiologia , Respiração/efeitos dos fármacos , Tronco Encefálico/efeitos dos fármacos , Rede Nervosa/efeitos dos fármacos
5.
Technol Cancer Res Treat ; 18: 1533033819857767, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31390948

RESUMO

PURPOSE: To develop a fusion imaging system that combines ultrasound and computed tomography for real-time tumor tracking and to validate the accuracy of performing registration via this approach during a specific breathing phase. MATERIALS AND METHODS: The initial part of the experimental study was performed using iodized oil injection in pig livers and was focused on determining the accuracy of registration. Eight points (A1-4 and B1-4) at different positions and with different target sizes were selected as target points. During respiratory motion, we used our self-designed system to perform the procedure either with (experimental group, E) or without (control group, C) the respiratory monitoring module. The registration errors were then compared between the 2 groups and within group E. The second part of this study was designed as a preliminary clinical study and was performed in 18 patients. Screening was performed to determine the combination of points on the body surface that provided the highest sensitivity to respiratory motion. Registration was performed either with (group E) or without (group C) the respiratory monitoring module. Registration errors were compared between the 2 groups. RESULTS: In part 1 of this study, there were fewer registration errors at each point in group E than at the corresponding points in group C (P < .01). In group E, there were more registration errors at points A1 and B1 than at the other points (P < .05). There was no significant difference in registration errors among the remaining points. During part 2 of the study, there was a significant difference in the registration errors between the 2 groups (P < .01). CONCLUSIONS: Real-time fusion registration is feasible and can be accurately performed during respiratory motions when using this system.


Assuntos
Neoplasias Hepáticas/diagnóstico por imagem , Fígado/diagnóstico por imagem , Imagem Multimodal/métodos , Respiração/efeitos dos fármacos , Animais , Humanos , Óleo Iodado/farmacologia , Neoplasias Hepáticas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Suínos , Tomografia Computadorizada por Raios X , Ultrassonografia
6.
PLoS One ; 14(8): e0220288, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31374096

RESUMO

The care and management of deer in captivity is challenging, especially in the case of red brocket deer (Mazama americana), whose routine management using physical restraint is difficult. Our study evaluated the effects of azaperone and xylazine combination for immobilizing red brocket deer and allow for the standard capture and handling protocols (e.g., biological material, horn cutting, and trimming) to be conducted safely. Six adult, captive, red brocket deer received an intramuscular injection of either 1 mg/kg azaperone and 0.5 mg/kg xylazine (AX0.5) or 1 mg/kg azaperone and 1 mg/kg xylazine (AX1.0). Sedation latency, sternal recumbency, safe handling, and quality of the sedation were evaluated to provide an overview of how the immobilizing drugs affected managing the species in captivity. Additionally, heart rate, respiratory rate, mean arterial pressure, rectal temperature, pH, PaO2, PaCO2, SaO2, HCO3-, BE, Na+, K+ and serum lactate were also measured. The latency period of the animals in the AX0.5 group was greater than that of the animals in the AX1.0 group (7 ± 6.6 min vs. 5 ± 2.0 min), as was the time for them to assume sternal recumbency (12 ± 9.7 min vs. 6 ± 3.1 min). However, the time after the initial dose at which the animals could safely be handled (14 ± 4.5 min vs. 12 ± 5.2 min), and the time until the end of the safe handling period (75 ± 12.3 min vs. 85 ± 6.8 min) were similar for both groups. Animals in both groups showed physiological stability during all evaluations, but hypoxemia was observed in one animal in each group. We conclude that both drug combinations are safe and effective at sedating red brocket deer in captivity and suggest that the procedure be performed with oxygen supplementation to reduce the potential for hypoxia.


Assuntos
Azaperona/farmacologia , Cervos , Imobilização/métodos , Xilazina/farmacologia , Animais , Relação Dose-Resposta a Droga , Feminino , Frequência Cardíaca/efeitos dos fármacos , Masculino , Respiração/efeitos dos fármacos
7.
Artigo em Chinês | MEDLINE | ID: mdl-31262103

RESUMO

Objective: To compare the parameters of polysomnography (PSG) in sleep structure and respiratory events between dexmedetomidine-induced sleep and natural sleep. Methods: From April 2016 to September 2018, a total of 44 patients with obstructive sleep apnea (OSA) and 3 patients with simple snoring completed PSG monitor both in natural sleep and dexmedetomidine-induced sleep in Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tsinghua Changgung Hospital. The PSG parameters were statistically analysed with SPSS 22.0 software. Results: The average dose of dexmedetomidine was (104.60±27.93) µg, and there was no significant difference between the induced-sleep efficiency and the natural sleep efficiency (82.14%±16.66% vs. 86.50%±9.18%, t=-1.559, P>0.05). There was no rapid eye movement(REM) stages in all 47 subjects and only 1 case of them had non-rapid eye movement(NREM) stage 3 in induced sleep. The percentage of NREM1 in total sleep time was statistically different between the two groups (42.10%±26.71% vs. 17.47%±11.68%, t=5.997, P<0.001),but there was no significant difference in the percentage of NREM2 in total sleep time between the two groups (56.96%±26.0% vs. 62.95%±9.03%, t=-1.521, P=0.135). About respiratory events, there were significant differences in apnea hypopnea index ((46.29±20.23)/h vs. (39.67±25.41)/h), obstructive apnea index (25.20[10.50,45.40]/h vs. 16.20[3.30,35.20]/h) between induced-sleep and natural sleep (t=2.297, Z=-3.008, all P<0.05), these difference were more significant in mild-to-moderate OSA. There were no statistically significant differences in central apnea index (0.00[0.00,2.80]/h vs. 0.40[0.10,1.20]/h), mixed apnea index (0.00[0.00,6.20]/h vs. 0.00[0.00,3.40]/h, hypopnea index (4.20[0.00,3.30]/h vs. 12.00[5.20,17.40]/h), Z=-0.110,-0.508,-1.544, all P>0.05). There were statistical differences in the lowest oxygen saturation (84.77%±7. 59% vs. 80.21%±11.62%, t=2.558, P=0.014). Conclusions: There is no significant difference in sleep efficiency and NREM2 between dexmedetomidine induced sleep and natural sleep.NREM3 sleep is rare induced, but REM sleep is none of all. And dexmedetomidine induced sleep may aggravate obstructive sleep apnea, but not central apnea.


Assuntos
Dexmedetomidina/farmacologia , Hipnóticos e Sedativos/farmacologia , Polissonografia , Apneia Obstrutiva do Sono/fisiopatologia , Sono , Ronco/fisiopatologia , Humanos , Respiração/efeitos dos fármacos , Sono/efeitos dos fármacos , Sono/fisiologia
8.
Rom J Ophthalmol ; 63(2): 142-145, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31334392

RESUMO

Purpose: To quantitatively evaluate the cardiopulmonary effects of various topical antiglaucoma drugs. Material & method: In this study, forty consecutive cases of newly diagnosed primary open angle glaucoma were recruited. After taking a detailed history, an ophthalmological examination and a systemic examination including resting pulse rate, blood pressure, ECG, auscultation of the chest and spirometry were performed. Then the patients were randomly divided into four groups and one of the four topical anti glaucoma medication (Timolol, Latanoprost, Brimonidine, and Dorzolamide) prescribed. Patients were reviewed 4 weeks later and the same ocular and systemic examinations were performed. Result: Timolol therapy reduced all the spirometry parameters that are statistically significant difference with the P value of less than 0.1. Timolol therapy resulted in the mean reduction of pulse rate by 3.2 beats/ minute and a mean reduction of systolic and diastolic blood pressure by 5.8 mmHg and 5.6 mmHg, respectively all the spirometry & cardiovascular parameters remained unchanged in the other three groups after 4 weeks of treatment. Conclusion: Timolol significantly affects the cardiopulmonary status. Therefore, we could advice the assessment of cardiopulmonary status mandatory in patients receiving topical beta-blockers. Bronchospasm may be of clinical significance in the elderly, who commonly have undiagnosed reversible airway obstruction.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Glaucoma de Ângulo Aberto/tratamento farmacológico , Frequência Cardíaca/efeitos dos fármacos , Respiração/efeitos dos fármacos , Timolol/administração & dosagem , Administração Tópica , Antagonistas Adrenérgicos beta/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas , Estudos Prospectivos , Espirometria
9.
Environ Int ; 131: 105021, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31349208

RESUMO

BACKGROUND: Indoor air pollution has emerged as a significant environmental and public health concern in recent years. However, evidence regarding the cardiorespiratory effects of indoor ozone is limited, and the underlying biological mechanisms are unclear, especially in children. Our study aimed to assess the cardiorespiratory responses to indoor ozone exposure in children. METHODS: A repeated-measure study was conducted in 46 middle-school children in Beijing, China. Real-time concentrations of ozone, along with co-pollutants including particulate matter (PM) and black carbon (BC), were monitored in classrooms from Monday to Friday. Three repeated health measurements of cardiorespiratory functions, including ambulatory electrocardiogram (ECG), blood pressure, fractional exhaled nitric oxide (FeNO) and lung function, were performed on each participant. Mixed-effect models were used to evaluate the effects of indoor ozone exposure. RESULTS: The mean (SD) indoor ozone concentration was 8.7 (6.6) ppb during the study period, which was largely below the current guideline and standards. However, even this low-level ozone exposure was associated with reduced cardiac autonomic function and increased heart rate (HR) in children. For instance, per interquartile range (IQR) increase in ozone at 2-hour moving average was associated with -7.8% (95% CI: -9.9%, -5.6%) reduction in standard deviation of all normal-to-normal intervals (SDNN), and 2.6% (95% CI: 1.6%, 3.6%) increment in HR. In addition, the associations were stronger at high BC levels (BC ≥ 3.7 µg/m3). No significant associations were found for airway inflammation and pulmonary function. CONCLUSIONS: Exposure to low-level indoor ozone that is not associated with respiratory effects was significantly related to disturbed cardiac autonomic function and increased HR in children, which suggested a possible mechanism through which ozone may affect cardiovascular health in children, and indicated more protective measures should be taken to alleviate the acute adverse effects of indoor ozone in this susceptible population.


Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar em Ambientes Fechados/efeitos adversos , Sistema Cardiovascular/efeitos dos fármacos , Ozônio/toxicidade , Respiração/efeitos dos fármacos , Adolescente , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Pequim , Criança , China , Exposição Ambiental , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Inflamação/induzido quimicamente , Masculino , Material Particulado/análise , Material Particulado/toxicidade , Fuligem/toxicidade
10.
Vet Anaesth Analg ; 46(4): 529-537, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31147260

RESUMO

OBJECTIVE: To compare the antinociceptive, sedative and cardiovascular effects of dexmedetomidine pharmacopuncture at Governing Vessel 1 (GV 1) with dexmedetomidine intramuscular (IM) administration. STUDY DESIGN: Randomized, masked crossover design. ANIMALS: A group of eight healthy female cats. METHODS: Cats were randomly administered either dexmedetomidine (0.005 mg kg-1; Dex-IM) IM or at acupuncture point GV 1 (Dex-P) separated by 1 week. Prior to and up to 120 minutes posttreatment, skin temperature (ST), thermal threshold (TT), heart rate (HR), respiratory rate (fR), sedation, muscle relaxation and auditory response scores were recorded. Parametric data were analyzed using a two-way repeated measures anova followed by Tukey's test for multiple comparisons. Nonparametric data were analyzed using a Friedman test followed by Dunn's multiple comparisons test, and Wilcoxon signed-rank test with Bonferroni correction for multiple comparisons. Significance was set at p ≤ 0.05. RESULTS: There were no differences within or between treatments for ST, fR and auditory response. TT was significantly higher at 30-90 minutes in Dex-P (p ≤ 0.0285) than baseline. TT was significantly higher at 60-90 minutes for Dex-P than for Dex-IM (p ≤ 0.0252). HR was significantly lower at 10-75 minutes in Dex-P (p ≤ 0.0378) and at 5-75 minutes in Dex-IM (p ≤ 0.0132) than baseline. Compared with baseline, sedation scores were higher at 25 minutes (p = 0.0327) and 30 minutes (p = 0.0327), and muscle relaxation scores were higher at 25 minutes (p = 0.0151) and 35 minutes (p = 0.0151) in Dex-P. There were no differences in HR, sedation and muscle relaxation scores between treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Dex-P increased thermal antinociception compared with Dex-IM at the same dose of dexmedetomidine in cats. This antinociceptive effect must be evaluated under clinical situations.


Assuntos
Analgesia por Acupuntura/veterinária , Gatos , Sedação Consciente/veterinária , Dexmedetomidina/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Dor/veterinária , Animais , Estudos Cross-Over , Dexmedetomidina/farmacologia , Feminino , Temperatura Alta , Relaxamento Muscular/efeitos dos fármacos , Distribuição Aleatória , Respiração/efeitos dos fármacos , Temperatura Cutânea/efeitos dos fármacos
11.
Toxicol Mech Methods ; 29(7): 542-548, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31172850

RESUMO

Plethysmograph measurement of respiratory phenotypes provides a highly sensitive means to study nicotine response in experimental model animals. We measured average respiratory frequency, tidal volume, minute volume and inspiratory time in C3H/HeJ and C57BL/6J mice subcutaneously administered 0.35 and 0.70 mg/kg nicotine. Both mouse strains showed significantly altered respiratory and locomotion phenotypes relative to saline-injected controls when administered the higher dose, but only C57BL/6J responded to the lower nicotine dose. Respiratory and locomotion phenotypes rarely differed significantly by sex. To investigate whether the strain-specific differences in nicotine sensitivity were related to differences in clearance, we followed up by measuring nicotine clearance in C3H/HeJ and C57BL/6J mice (0.35 mg/kg subcutaneous) and found sex differences in both strains, but no difference between strains.


Assuntos
Nicotina/toxicidade , Respiração/efeitos dos fármacos , Especificidade da Espécie , Animais , Feminino , Injeções Subcutâneas , Masculino , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Nicotina/administração & dosagem , Nicotina/sangue , Nicotina/metabolismo , Pletismografia Total
12.
Vet Anaesth Analg ; 46(4): 483-487, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31178411

RESUMO

OBJECTIVE: To describe clinically relevant, physiological measurements collected during a 3 hour duration of alfaxalone total intravenous anaesthesia. STUDY DESIGN: Case series. ANIMALS: A total of 112 client-owned middle-aged or older dogs. METHODS: Dogs were premedicated with intramuscular acepromazine (0.03 mg kg-1). Anaesthesia was induced and subsequently maintained for up to 3 hours with alfaxalone administered intravenously. Dogs breathed 100% oxygen via an endotracheal tube. Heart rate, respiratory rate and blood pressure were evaluated 30 minutes after administration of acepromazine and used as baseline values for comparisons of intra-anaesthetic data. Blood glucose was measured 1 week prior to anaesthesia and every hour during alfaxalone anaesthesia. Quality and duration of recovery were recorded. Mean data for physiological variables were compared over three time points-before induction of anaesthesia, for the first hour of anaesthesia and from 60 minutes to discontinuation of anaesthesia. RESULTS: Mean induction dose of alfaxalone was 1.4 mg kg-1 [95% confidence interval (CI) 1.3-1.5). Post induction apnoea for >60 seconds occurred in 13 (11.6%) dogs. Mean alfaxalone infusion rate during the first 60 minutes of anaesthesia was 0.099 mg kg-1 minute-1; mean infusion rate was 0.092 mg kg-1 minute-1 from 60 minutes until discontinuation of anaesthesia. Heart rate was well maintained; hypotension (mean arterial blood pressure < 60 mmHg) was encountered in 23 (21%) dogs. Blood glucose levels did not alter during anaesthesia. Median time between discontinuation of alfaxalone infusion and extubation was 17 (7-35 minutes), time to assuming sternal recumbency was 75 (58-110 minutes), and time to standing was 109 (88-140 minutes). CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone infusion provided effective anaesthesia in this population. In a minority of cases, respiratory and haemodynamic support of the patient was required.


Assuntos
Anestesia Intravenosa/veterinária , Anestésicos/farmacologia , Doenças do Cão/diagnóstico por imagem , Osteoartrite/veterinária , Pregnanodionas/farmacologia , Radiografia/veterinária , Anestésicos/administração & dosagem , Anestésicos/efeitos adversos , Animais , Apneia/induzido quimicamente , Apneia/veterinária , Glicemia , Pressão Sanguínea/efeitos dos fármacos , Dióxido de Carbono/sangue , Estudos de Casos e Controles , Cães , Feminino , Frequência Cardíaca/efeitos dos fármacos , Masculino , Osteoartrite/diagnóstico por imagem , Oxigênio/sangue , Pregnanodionas/administração & dosagem , Pregnanodionas/efeitos adversos , Respiração/efeitos dos fármacos
13.
Anesthesiology ; 131(3): 467-476, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31045894

RESUMO

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: The ventilatory response to hypoxia is a critical reflex that is impaired by neuromuscular blocking drugs. However, the degree to which this reflex is restored after reversal of blockade is unknown. WHAT THIS ARTICLE TELLS US THAT IS NEW: Despite full reversal of neuromuscular blockade at the thumb using different drug classes, this hypoxic chemoreflex is not fully restored. BACKGROUND: The ventilatory response to hypoxia is a life-saving chemoreflex originating at the carotid bodies that is impaired by nondepolarizing neuromuscular blocking agents. This study evaluated the effect of three strategies for reversal of a partial neuromuscular block on ventilatory control in 34 healthy male volunteers on the chemoreflex. The hypothesis was that the hypoxic ventilatory response is fully restored following the return to a train-of-four ratio of 1. METHODS: In this single-center, experimental, randomized, controlled trial, ventilatory responses to 5-min hypoxia (oxygen saturation, 80 ± 2%) and ventilation at hyperoxic isohypercapnia (end-tidal carbon dioxide concentration, 55 mmHg) were obtained at baseline, during rocuronium-induced partial neuromuscular block (train-of-four ratio of 0.7 measured at the adductor pollicis muscle by electromyography), and following reversal until the train-of-four ratio reached unity with placebo (n = 12), 1 mg neostigmine/0.5 mg atropine (n = 11), or 2 mg/kg sugammadex (n = 11). RESULTS: This study confirmed that low-dose rocuronium reduced the ventilatory response to hypoxia from 0.55 ± 0.22 (baseline) to 0.31 ± 0.21 l · min · % (train-of-four ratio, 0.7; P < 0.001). Following full reversal as measured at the thumb, there was persistent residual blunting of the hypoxic ventilatory response (0.45 ± 0.16 l · min · %; train-of-four ratio, 1.0; P < 0.001). Treatment effect was not significant (analysis of covariance, P = 0.299) with chemoreflex impairment in 5 (45%) subjects following sugammadex reversal, in 7 subjects (64%) following neostigmine reversal, and in 10 subjects (83%) after spontaneous reversal to a train-of-four ratio of 1. CONCLUSIONS: Despite full reversal of partial neuromuscular block at the thumb, impairment of the peripheral chemoreflex may persist at train-of-four ratios greater than 0.9 following reversal with neostigmine and sugammadex or spontaneous recovery of the neuromuscular block.


Assuntos
Hipóxia/fisiopatologia , Neostigmina/farmacologia , Bloqueio Neuromuscular/métodos , Respiração/efeitos dos fármacos , Rocurônio/antagonistas & inibidores , Sugammadex/farmacologia , Adolescente , Adulto , Período de Recuperação da Anestesia , Inibidores da Colinesterase/farmacologia , Método Duplo-Cego , Eletromiografia , Voluntários Saudáveis , Humanos , Masculino , Fármacos Neuromusculares não Despolarizantes/antagonistas & inibidores , Adulto Jovem
14.
Environ Int ; 129: 291-298, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31146163

RESUMO

Wildfires have been increasing in frequency in the western United States (US) with the 2017 and 2018 fire seasons experiencing some of the worst wildfires in terms of suppression costs and air pollution that the western US has seen. Although growing evidence suggests respiratory exacerbations from elevated fine particulate matter (PM2.5) during wildfires, significantly less is known about the impacts on human health of ozone (O3) that may also be increased due to wildfires. Using machine learning, we created daily surface concentration maps for PM2.5 and O3 during an intense wildfire in California in 2008. We then linked these daily exposures to counts of respiratory hospitalizations and emergency department visits at the ZIP code level. We calculated relative risks of respiratory health outcomes using Poisson generalized estimating equations models for each exposure in separate and mutually-adjusted models, additionally adjusted for pertinent covariates. During the active fire periods, PM2.5 was significantly associated with exacerbations of asthma and chronic obstructive pulmonary disease (COPD) and these effects remained after controlling for O3. Effect estimates of O3 during the fire period were non-significant for respiratory hospitalizations but were significant for ED visits for asthma (RR = 1.05 and 95% CI = (1.022, 1.078) for a 10 ppb increase in O3). In mutually-adjusted models, the significant findings for PM2.5 remained whereas the associations with O3 were confounded. Adjusted for O3, the RR for asthma ED visits associated with a 10 µg/m3 increase in PM2.5 was 1.112 and 95% CI = (1.087, 1.138). The significant findings for PM2.5 but not for O3 in mutually-adjusted models is likely due to the fact that PM2.5 levels during these fires exceeded the 24-hour National Ambient Air Quality Standard (NAAQS) of 35 µg/m3 for 4976 ZIP-code days and reached levels up to 6.073 times the NAAQS, whereas our estimated O3 levels during the fire period only occasionally exceeded the NAAQS of 70 ppb with low exceedance levels. Future studies should continue to investigate the combined role of O3 and PM2.5 during wildfires to get a more comprehensive assessment of the cumulative burden on health from wildfire smoke.


Assuntos
Ozônio/toxicidade , Material Particulado/toxicidade , Respiração/efeitos dos fármacos , Incêndios Florestais , Poluição do Ar , Asma/induzido quimicamente , California , Serviço Hospitalar de Emergência , Hospitalização , Humanos , Risco , Estações do Ano
15.
Anesth Analg ; 129(2): 458-474, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31082964

RESUMO

The majority of women undergoing cesarean delivery in the United States receive neuraxial morphine, the most effective form of postoperative analgesia for this surgery. Current American Society of Anesthesiologists (ASA) and American Society of Regional Anesthesia and Pain Medicine (ASRA) recommend respiratory monitoring standards following neuraxial morphine administration in the general surgical population that may be too frequent and intensive when applied to the healthy obstetric population receiving a single dose of neuraxial morphine at the time of surgery. There is limited evidence to support or guide the optimal modality, frequency, and duration of respiratory monitoring in the postoperative cesarean delivery patient receiving a single dose of neuraxial morphine. Consistent with the mission of the Society for Obstetric Anesthesia and Perinatology (SOAP) to improve outcomes in pregnancy for women and neonates, the purpose of this consensus statement is to encourage the use of this highly effective analgesic technique while promoting safe practice and patient-centered care. The document aims to reduce unnecessary interruptions from respiratory monitoring in healthy mothers while focusing vigilance on monitoring in those women at highest risk for respiratory depression following neuraxial morphine administration. This consensus statement promotes the use of low-dose neuraxial morphine and multimodal analgesia after cesarean delivery, gives perspective on the safety of this analgesic technique in healthy women, and promotes patient risk stratification and perioperative risk assessment to determine and adjust the intensity, frequency, and duration of respiratory monitoring.


Assuntos
Analgesia Obstétrica , Analgésicos Opioides/administração & dosagem , Cesárea , Pulmão/efeitos dos fármacos , Morfina/administração & dosagem , Dor Pós-Operatória/prevenção & controle , Respiração/efeitos dos fármacos , Insuficiência Respiratória/prevenção & controle , Analgesia Obstétrica/efeitos adversos , Analgésicos Opioides/efeitos adversos , Cesárea/efeitos adversos , Consenso , Esquema de Medicação , Feminino , Humanos , Pulmão/fisiopatologia , Morfina/efeitos adversos , Dor Pós-Operatória/etiologia , Gravidez , Insuficiência Respiratória/induzido quimicamente , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/fisiopatologia , Medição de Risco , Fatores de Risco , Resultado do Tratamento
16.
Neurobiol Dis ; 127: 591-604, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31028873

RESUMO

We tested a biomaterial-based approach to preserve the critical phrenic motor circuitry that controls diaphragm function by locally delivering minocycline hydrochloride (MH) following cervical spinal cord injury (SCI). MH is a clinically-available antibiotic and anti-inflammatory drug that targets a broad range of secondary injury mechanisms via its anti-inflammatory, anti-oxidant and anti-apoptotic properties. However, MH is only neuroprotective at high concentrations that cannot be achieved by systemic administration, which limits its clinical efficacy. We have developed a hydrogel-based MH delivery system that can be injected into the intrathecal space for local delivery of high concentrations of MH, without damaging spinal cord tissue. Implantation of MH hydrogel after unilateral level-C4/5 contusion SCI robustly preserved diaphragm function, as assessed by in vivo recordings of compound muscle action potential (CMAP) and electromyography (EMG) amplitudes. MH hydrogel also decreased lesion size and degeneration of cervical motor neuron somata, demonstrating its central neuroprotective effects within the injured cervical spinal cord. Furthermore, MH hydrogel significantly preserved diaphragm innervation by the axons of phrenic motor neurons (PhMNs), as assessed by both detailed neuromuscular junction (NMJ) morphological analysis and retrograde PhMN labeling from the diaphragm using cholera toxin B (CTB). In conclusion, our findings demonstrate that local MH hydrogel delivery to the injured cervical spinal cord is effective in preserving respiratory function after SCI by protecting the important neural circuitry that controls diaphragm activation.


Assuntos
Medula Cervical/lesões , Hidrogéis/uso terapêutico , Minociclina/uso terapêutico , Rede Nervosa/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Medula Cervical/efeitos dos fármacos , Medula Cervical/fisiopatologia , Diafragma/efeitos dos fármacos , Diafragma/fisiopatologia , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Feminino , Hidrogéis/administração & dosagem , Minociclina/administração & dosagem , Rede Nervosa/fisiopatologia , Fármacos Neuroprotetores/administração & dosagem , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Respiração/efeitos dos fármacos , Traumatismos da Medula Espinal/fisiopatologia
17.
Dent Med Probl ; 56(1): 75-80, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30951622

RESUMO

BACKGROUND: Methyl methacrylate (MMA) is one of the widely used organic monomers in dentistry. It may cause multiple adverse reactions, ranging from allergic reaction to systemic toxicity. Dentistry students are exposed to MMA in an acute manner; however, the concentration of its vapor cannot be estimated well. OBJECTIVES: The aim of this study was to evaluate the effect of acute MMA vapor inhalation on the pulmonary function of dental students, both smokers and non-smokers. MATERIAL AND METHODS: Thirty-eight male dental students were divided into 2 groups (group 1 - smokers and group 2 - non-smokers). The lung function parameters of the students were tested with a spirometer during their ordinary training work in a prosthodontics laboratory, before contact with MMA and immediately after it. The lung function test was performed using a standard protocol. The students were asked not to use any perfume or aromatic overlaps for a period of 24 h before starting the tests. RESULTS: The researchers noted a statistically significant decrease (p ≤ 0.05) in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), peak expiratory flow (PEF), forced expiratory flow at 25-75% of the pulmonary volume (FEF25-75), and forced expiratory flow at 25% (FEF25) and 50% (FEF50) of the pulmonary volume in smokers and non-smokers by comparing the preand post-work tests. CONCLUSIONS: Acute inhalation of MMA vapor induced a moderate restriction of pulmonary function in dental students, both smokers and non-smokers, during their routine prosthodontics laboratory training work. No differences in the results of the pulmonary function tests between smokers and non-smokers were observed.


Assuntos
Odontologia , Metilmetacrilato , não Fumantes , Exposição Ocupacional , Respiração , Fumantes , Estudantes , Humanos , Masculino , Metilmetacrilato/farmacologia , Exposição Ocupacional/efeitos adversos , Respiração/efeitos dos fármacos , Testes de Função Respiratória , Fumar
18.
Med Sci Monit ; 25: 1806-1813, 2019 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-30851162

RESUMO

BACKGROUND Patients with obstructive sleep apnea syndrome (OSAS) are at an increased risk of cardiovascular disease. The aims of this study were to develop a rat model of OSAS and to validate the use of the model by investigating respiratory and cardiovascular physiological parameters and morphological changes by light microscopy and electron microscopy. MATERIAL AND METHODS Sixty 3-month-old Sprague-Dawley rats were assigned to the model group (n=30) and the control group (n=30). The rats in the OSAS model group were injected with 0.1 ml sodium hyaluronate solution into the upper respiratory tract at the junction between the hard and soft palate. After one month, the model and normal rats were compared using tests of respiratory and cardiac function, and histology and electron microscopy of the lung and cardiac tissue. RESULTS In the rat model of OSAS, airway obstruction resulted in the collapse of the upper airway. Tests of respiratory function showed that the oxygen partial pressure, oxygen concentration, and oxygen saturation in the model group were significantly lower when compared with the control group. In the model group, histology of the heart showed cardiac myocyte disarray, and electron microscopy showed vacuolar degeneration and mitochondrial abnormalities. The rat model of upper airway occlusion showed pulmonary and cardiac changes that have been described in OSAS. CONCLUSIONS A rat model of upper airway occlusion resulted in physiological and morphological changes in the lung and heart due to hypoxia, and may be used for future studies on OSAS.


Assuntos
Apneia Obstrutiva do Sono/metabolismo , Apneia Obstrutiva do Sono/fisiopatologia , Animais , Cardiomiopatias/fisiopatologia , Modelos Animais de Doenças , Feminino , Testes de Função Cardíaca , Ácido Hialurônico , Pulmão/citologia , Masculino , Miocárdio/citologia , Ratos , Ratos Sprague-Dawley , Respiração/efeitos dos fármacos , Testes de Função Respiratória
19.
J Neuromuscul Dis ; 6(2): 213-225, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30856119

RESUMO

BACKGROUND: Duchenne muscular dystrophy (DMD) patients experience skeletal muscle degeneration, including respiratory muscles. Respiratory decline in glucocorticoid-treated DMD patients, measured by percent predicted forced vital capacity (FVC% p), is typically 5% annually in patients aged 10 to 18 years. OBJECTIVE: Evaluate the effects of eteplirsen on FVC% p annual change in 3 trials versus matched Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS) controls. METHODS: Eteplirsen studies 201/202 evaluated eligible ambulatory DMD patients for at least 4 years, study 204 evaluated primarily non-ambulatory DMD patients for 2 years, and ongoing study 301 is evaluating ambulatory DMD patients for 2 years (interim analysis is included). Eteplirsen-treated patients (n = 74) were amenable to exon 51 skipping and were receiving glucocorticoids. Three CINRG DNHS cohorts included: glucocorticoid-treated patients amenable to exon 51 skipping (Exon 51 CINRG DNHS; n = 20), all glucocorticoid-treated CINRG patients (All CINRG DNHS; n = 172), and all glucocorticoid-treated genotyped CINRG DNHS patients (Genotyped CINRG DNHS; n = 148). FVC% p assessments between ages 10 and <18 years were included for all patients; mixed-model analyses characterized FVC% p annual change. RESULTS: FVC% p annual change was greater for CINRG DNHS Exon 51 controls (- 6.00) versus patients in studies 201/202, study 204, and study 301 (- 2.19, P < 0.001; - 3.66, P 0.004; and - 3.79, P 0.017, respectively). FVC% p annual change in all eteplirsen studies suggested treatment benefit compared with the Genotyped CINRG DNHS (- 5.67) and All CINRG DNHS (- 5.56) cohorts (P < 0.05, all comparisons). CONCLUSIONS: Significant, clinically meaningful attenuation of FVC%p decline was observed in eteplirsen-treated patients versus CINRG DNHS controls.


Assuntos
Ensaios Clínicos como Assunto , Morfolinos/uso terapêutico , Distrofia Muscular de Duchenne/tratamento farmacológico , Respiração/efeitos dos fármacos , Capacidade Vital/efeitos dos fármacos , Adolescente , Criança , Humanos , Masculino
20.
Equine Vet J ; 51(5): 646-652, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30793362

RESUMO

BACKGROUND: Medetomidine suppresses cardiovascular function and reduces gastrointestinal motility in horses mainly through peripheral α2 -adrenoceptors. Vatinoxan, a peripheral α2 -antagonist, has been shown experimentally to alleviate the adverse effects of some α2 -agonists in horses. However, vatinoxan has not been investigated during constant-rate infusion (CRI) of medetomidine in standing horses. OBJECTIVES: To evaluate effects of vatinoxan on cardiovascular function, gastrointestinal motility and on sedation level during CRI of medetomidine. STUDY DESIGN: Experimental, randomised, blinded, cross-over study. METHODS: Six healthy horses were given medetomidine hydrochloride, 7 µg/kg i.v., without (MED) and with (MED+V) vatinoxan hydrochloride, 140 µg/kg i.v., followed by CRI of medetomidine at 3.5 µg/kg/h for 60 min. Cardiorespiratory variables were recorded and borborygmi and sedation levels were scored for 120 min. Plasma drug concentrations were measured. The data were analysed using repeated measures ANCOVA and paired t-tests as appropriate. RESULTS: Initially heart rate (HR) was significantly lower and mean arterial blood pressure (MAP) significantly higher with MED compared with MED+V. For example at 10 min HR (mean ± s.d.) was 26 ± 2 and 31 ± 5 beats/minute (P = 0.04) and MAP 129 ± 15 and 103 ± 13 mmHg (P<0.001) respectively. At 10 min, cardiac index was lower (P = 0.02) and systemic vascular resistance higher (P = 0.001) with MED than with MED+V. Borborygmi were reduced after MED; this effect was attenuated by vatinoxan (P<0.001). All horses were sedated with medetomidine, but the mean sedation scores were reduced with MED+V until 20 min (6.8 ± 0.8 and 4.5 ± 1.5 with MED and MED+V, respectively, at 10 min, P = 0.001). Plasma concentration of dexmedetomidine was significantly lower in the presence of vatinoxan (P = 0.01). MAIN LIMITATIONS: Experimental study with healthy, unstimulated animals. CONCLUSIONS: Vatinoxan administered i.v. with a loading dose of medetomidine improved cardiovascular function and gastrointestinal motility during medetomidine CRI in healthy horses. Sedation was slightly yet significantly reduced during the first 20 min.. The Summary is available in Portuguese - see Supporting Information.


Assuntos
Motilidade Gastrointestinal/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Cavalos , Medetomidina/farmacologia , Quinolizinas/farmacologia , Respiração/efeitos dos fármacos , Animais , Área Sob a Curva , Estudos Cross-Over , Feminino , Meia-Vida , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Masculino , Medetomidina/metabolismo , Medetomidina/farmacocinética , Quinolizinas/administração & dosagem , Resistência Vascular/efeitos dos fármacos
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