The role of dopamine in directly modulating somatic motoneuron excitability and hence muscle tone is unknown. We investigated whether dopamine influences the trigeminal motor pool (MoV) that innervates the masseter and tensor palatini muscles, both of which function to maintain upper airway patency. We hypothesized that dopamine facilitates motor outflow at the MoV. We focally applied apomorphine (nonspecific dopamine receptor agonist) at the MoV in anaesthetized rats. We also applied receptor-specific agonists and antagonists to determine the receptor subtype mediating dopaminergic mechanisms of action. We demonstrated that dopaminergic transmission at the MoV potently increased motor outflow via the D1-like receptor and facilitated masseter and tensor palatini muscle tone. It is unknown whether endogenous dopamine release on to airway motoneurons influences their activity to regulate muscle tone in natural sleep-wake behaviours. This issue warrants investigation because the neurochemical basis of upper airway motor dysfunction (e.g. obstructive sleep apnea) remains poorly characterized.

The role of dopamine in directly modulating somatic motoneuron excitability and hence muscle tone is unknown. We investigated whether dopamine influences the trigeminal motor pool (MoV) that innervates the masseter and tensor palatini muscles, both of which function to maintain upper airway patency. We hypothesized that dopamine facilitates motor outflow at the MoV. We focally applied apomorphine (nonspecific dopamine receptor agonist) at the MoV in anaesthetized rats. We also applied receptor-specific agonists and antagonists to determine the receptor subtype mediating dopaminergic mechanisms of action. We demonstrated that dopaminergic transmission at the MoV potently increased motor outflow via the D1-like receptor and facilitated masseter and tensor palatini muscle tone. It is unknown whether endogenous dopamine release on to airway motoneurons influences their activity to regulate muscle tone in natural sleep-wake behaviours. This issue warrants investigation because the neurochemical basis of upper airway motor dysfunction (e.g. obstructive sleep apnea) remains poorly characterized.

No description available.

Background: Obstructive sleep apnea is a common disorder, especially in men. Patients with this condition often snore and suffer from excessive daytime sleepiness. It is a treatable condition related to cardiovascular disease, road traffic accidents and obesity. Aims: To study whether snoring and witnessed sleep apnea are related to diabetes mellitus and whether sleepy subjects who snore or report sleep apneas drive more than others. To investigate whether sleep apnea is related to stroke, mortality and myocardial infarction in patients with coronary artery disease. To study the effect of ambient temperature on sleep apnea, morning alertness and sleep quality in patients with obstructive sleep apnea. Methods and results: Questions on snoring, sleep apnea, daytime sleepiness and yearly driving distance were included in the northern Sweden component of the WHO MONICA study. Analyzed were 7905 randomly selected men and women aged 25-79 years. Snoring and witnessed sleep apnea were related to diabetes mellitus in women, (OR 1.58, p = 0.041 and OR 3.29, p = 0.012 respectively), independent of obesity, age and smoking, but not in men. Sleepy snoring men drove a mean of 22566 km per year which was more than others who drove 17751 km per year independent of age, BMI, smoking and physical activity (p = 0.02). Sleepy men reporting sleep apnea also drove more (p = 0.01). 392 men and women with coronary artery disease referred for coronary angiography were examined with overnight sleep apnea recordings and followed for 10 years. Sleep apnea was recorded in 211 (54%) of patients at baseline. Stroke occurred in 47 (12%) patients at follow up. Sleep apnea was associated with an increased risk of stroke (HR 2.89, 95% CI 1.37 - 6.09, p = 0.005) independent of age , BMI, left ventricular function, diabetes mellitus, gender, intervention, hypertension, atrial fibrillation, a previous stroke or TIA and smoking. The risk of stroke increased with the severity of sleep apnea. 40 patients with obstructive sleep apnea were investigated with overnight polysomnography in ambient temperatures of 16°C, 20°C and 24°C in random order. Total sleep time was a mean of 30 minutes longer (p = 0.009), sleep efficiency higher (p = 0.012), patients were more alert in the morning (p = 0.028), but sleep apnea was more severe when sleeping in 16°C (p = 0.001) and 20°C (p = 0.033) vs. 24°C. The AHI was 30 ± 17 in 16ºC room temperature, 28 ± 17 in 20°C and 24 ± 18 in 24°C. Conclusions: Snoring and witnessed sleep apneas are related to diabetes mellitus in women. Sleepy men who snore or report sleep apnea drive more than others. Sleep apnea is independently associated with the risk of stroke among patients with coronary artery disease. Subjects with obstructive sleep apnea sleep longer, are more alert in the morning after a night’s sleep, but sleep apnea is more severe when sleeping in a colder environment.

Introdução: O desenvolvimento de hipertensão arterial e doença cardiovascular relacionado à síndrome das apnéia obstrutiva do sono (SAOS) parece estar relacionado a alterações sobre a regulação autonômica cardiovascular. Este estudo investigou se a SAOS influência a variabilidade da pressão arterial (PA). Métodos: Estudo transversal, com pacientes hipertensos que foram submetidos à polissonografia nível III, por meio de um monitor portátil de uso domiciliar para detectar SAOS (índice de apnéia-hipopnéia (IAH) ≥ 10). A variabilidade da PA foi avaliada pela taxa de variação da pressão arterial no tempo (índice “time rate” - a primeira derivada da pressão arterial ao longo do tempo) e desvio padrão (DP) da PA obtidos dos dados da monitorização ambulatorial da pressão arterial (MAPA). Análises univariadas e multivariadas foram utilizadas para testar a associação entre a SAOS, IAH e variabilidade da pressão arterial. Resultados: Os pacientes com SAOS (n = 57) eram mais velhos, apresentavam pressão arterial mais elevada e maior duração da hipertensão do que pacientes sem SAOS (n = 50). Não houve nenhuma associação consistente entre o diagnóstico de SAOS e variabilidade da PA aferida pelo DP e pela taxa de variação da PA no tempo, tanto na análise univariada como após o ajuste para idade, IMC e respectiva medida de PA na MAPA. Não houve correlação significativa entre o AIH e os índices de variabilidade da PA em um modelo de regressão linear múltipla, controlando para idade, IMC e PA correspondente. Conclusão: SAOS não influencou a variabilidade da pressão arterial, aferida por estes métodos, em pacientes com hipertensão. / Background The risk of obstructive sleep apnea syndrome (OSAS) for the development of hypertension and cardiovascular disease may be intermediate by influence over autonomic cardiovascular regulation. This study investigated if OSAS influences blood pressure (BP) variability. Methods In a cross-sectional study, patients with hypertension underwent level III polysomnography by means of a home portable monitor to detect OSAS, (apnea-hypopnea index (AHI) ≥10). BP variability was assessed by the time rate index (the first derivative of BP over time) and standard deviation (SD) of BP measured by 24-h ambulatory blood pressure measurement (ABPM). The association between OSAS, AHI and blood pressure variability was tested by univariate and multivariate methods. Results: Patients with OSAS (n = 57) were older, had higher blood pressure, and longer duration of hypertension than patients without OSAS (n = 50). There was no consistent association between the diagnosis of OSAS and BP variability assessed by the time-rate index and SD both in the univariate and after adjustment for age, BMI and the respective BP. There was no significant correlation between AIH and the indexes of BP variability in a multiple linear regression model controlling for age, BMI and the corresponding BP. Conclusion OSAS does not influence blood pressure variability in patients with hypertension.

Orientador: Silke Anna Thereza Weber / Resumo: Objetivo: Identificar preditores de risco para complicações respiratórias após adenotonsilectomia (AT) em crianças menores que 12 anos com AOS que aguardam cirurgia, bem como a prevalência e gravidade da AOS. Métodos: Estudo prospectivo em hospital escola da Faculdade de Medicina de Botucatu. Foram incluídas crianças de ambos os gêneros, 2 a 12 anos de idade, com AOS e indicação de AT. Todos realizaram polissonografia de noite inteira no pré- e pós-operatório. Foram utilizados o teste t independente, teste t dependente, Mann-Whitney, Kruskal-Wallis e Qui-quadrado para identificação de fatores de risco para morbidade respiratória após AT e estratificação da AOS. Resultados: As 82 crianças que realizaram AT foram divididas em 2 grupos de acordo com presença ou ausência de complicações respiratórias. Dezesseis crianças (20%), com idade média de 8,2 + 2,4 anos, apresentaram complicações respiratórias, sendo 9 gênero masculino. Foram observadas complicações respiratórias menores (SpO2 80 - 90%) e maiores (SpO2 < 80%, broncoespasmos intra- e pós-operatório e depressão respiratória). Asma, rinopatia e déficit de atenção foram preditores independentes de complicações respiratórias após AT. Entre as intervenções médicas, 1 criança realizou NBZ contínuas com broncodilatador, 6 necessitaram de reposicionamento de via aérea e NBZ com O2 suplementar e 1 fez uso de Narcan para reverter depressão respiratória. A prevalência de AOS em crianças de 2 a 12 anos foi de 93% (76 crianças), sendo 3... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor

Introduction: Obstructive sleep apnea (OSA) is a common breathing disorder with numerous health consequences, including greater risk of complications perioperatively. Undiagnosed OSA is known to place surgical patients at a higher risk of serious adverse events, including stroke and death. Polysomnography (PSG) assessment is the current gold standard test for diagnosing OSA. However, due to the significant time commitment and cost associated with PSG, a substantial number of OSA patients go undiagnosed before the perioperative period. Although the STOP-Bang questionnaire screening tool is currently used to help detect OSA patients, the low specificity to screen people without the disease is considered a major limitation. There is a clear need to develop a quick and effective prediction rule with higher overall accuracy to help streamline OSA diagnosis. Tracheal breathing sound analysis in awake patients at the bedside has shown potential to screen OSA patients with higher specificity compared to the STOP-Bang questionnaire. To date, no screening tools exist to detect OSA patients that combine the results of breathing sound analysis and STOP-Bang. Objectives: The present study aimed to develop a prediction rule, using both breathing sound analysis and variables in the STOP-Bang questionnaire, to better streamline the diagnosis of OSA. Methods: This prospective cohort study recruited patients referred for PSG at the Ottawa Hospital Sleep Centre from November 2016 to May 2017. The study conduct was approved by the Ottawa Health Science Network Research Ethics Board (#20160494-01H). After obtaining informed consent, anthropomorphic, breathing sound recordings, and STOP-Bang questionnaire data was collected from over 400 consenting patients. All patients that met the eligibility criteria were included. The breathing sound analysis and STOP-Bang results were utilized to design a prediction rule using logistic regression. Sensitivity, specificity, and likelihood ratio were used to compare the diagnostic performance of the final model. Results: Of the 439 consenting study participants, 280 study participants data were eligible for inclusion in the logistic regression analysis. Physician sleep specialists diagnosed 114 participants (41%) with moderate-to-severe OSA and 166 participants (59%) with normal-to-mild OSA. At a predicted probability of moderate-to-severe OSA greater than or equal to 0.5, breathing sound analysis had a similar sensitivity of 75.9 (95%CI; 65.4, 82.0) and higher specificity of 74.5% (95%CI; 68.5, 82.0) when compared to STOP-Bang with a sensitivity and specificity of 68.4% (95%CI; 58.9, 76.6) and 63.2% (95%CI: 55.0, 70.1), respectively. The sensitivity and specificity for the Safe-OSA rule, obtained by combining breathing sound analysis and STOP-Bang variables, were determined to be 75.4% (95%CI; 65.4, 82.0) and 74.5% (95%CI; 68.5, 82.0), respectively. A sensitivity analysis using a likelihood ratio test showed that breathing sound analysis contributed significantly to the performance of the Safe-OSA rule. The Safe-OSA rule was determined to be reasonably discriminative and well calibrated. The five-fold cross-validation showed similar results for the final model in the derivation and testing subsamples, which provides support for the internal validity of the Safe-OSA rule in our study population. Conclusion: The present study lends further support for the future testing of tracheal breathing sound analysis as a potential method to screen for moderate-to-severe OSA to help streamline patient care in the perioperative setting. Trial registration: ClinicalTrials.gov identifier NCT02987283.

Realizamos um estudo transversal prospectivo com o objetivo de determinar a prevalência de apnéia obstrutiva do sono em um grupo de pacientes sul-americanos com mucopolissacaridose tipo VI sem tratamento prévio ou atual com terapia de reposição enzimática ou transplante de medula óssea. Os critérios de inclusão foram: ter 4 anos ou mais de idade e confirmação bioquímica da doença (níveis reduzidos da atividade da arilsulfatase B, aumento de glicosaminoglicanos (GAGs) urinários e atividade normal de outra sulfatase). Foram avaliados 28 pacientes através de anamnese, exame físico, ecocardiograma Doppler transtorácico e polissonografia realizada em noite inteira. A amostra estudada tinha 14 (50%) meninos. No momento da avaliação, a média de idade foi de 98,5 meses e a média de idade do diagnóstico de MPS VI foi de 48,4 meses. Em 88% da amostra os sintomas iniciaram com menos de 36 meses e em 27% das famílias houve relato de consangüinidade entre os pais. As manifestações clínicas mais freqüentes durante o sono foram roncos e apnéias observadas. Ao exame físico, 78,6% apresentavam macroglossia e 82,1% deformidade torácica tipo pectus carinatum. Três (10,71%) pacientes já tinham realizado adenotonsilectomia e 6 (21,42%) adenoidectomia isoladamente. Os dados polissonográficos evidenciaram apnéia obstrutiva do sono em 23 (85,1%) pacientes, sendo 4 com transtorno leve, 5 moderado e 14 grave. A média do índice de apnéia hipopnéia (IAH) foi de 19,84 ± 26,25 eventos/hora, da saturação periférica da oxihemoglobina (SpO2) 93,25 ± 5,06%, do nadir da SpO2 80,29 ± 10,01% e do pico do dióxido de carbono final exalado (EtCO2) 44,1 ± 6,01 mmHg. A ocorrência de apnéias centrais foi rara. Quatorze indivíduos da amostra (50%) tiveram evidência de hipertensão pulmonar (HP) documentada através de ecocardiograma. Foi observada associação positiva entre a média e o nadir da SpO2 mais baixos e a presença de HP. No grupo com HP, a média e o nadir da SpO2 foram de 91,2 ± 6,4% e 75,4 ± 10,9% respectivamente, enquanto que nos pacientes sem HP os valores de média e nadir da SpO2 foram 95,3 ± 1,8% e 85,2 ± 6,1% respectivamente (p=0,037 para média; p=0,007 para nadir). A presença de apnéias observadas durante o sono foi a variável mais importante em predizer HP nessa amostra (p=0,016; OR 9,9; IC 1,5 a 63,7). As manifestações clínicas sugestivas de alterações respiratórias durante o sono não apresentaram correlação significativa com o IAH, a média e o nadir de SpO2 e o pico de EtCO2. Também não houve correlação significativa entre a excreção urinária de GAGS e a atividade enzimática com resultado da polissonografia e do ecocardiograma. Concluímos que a prevalência de apnéia obstrutiva do sono nos pacientes com mucopolissacaridose tipo VI é elevada e o nível de dessaturação apresenta correlação positiva com a presença de hipertensão pulmonar. Os sintomas durante o sono não apresentaram associação com o resultado da polissonografia. A presença de apnéias observadas durante o sono foi a variável mais importante para predizer HP. / This prospective cross-sectional study was conducted to determine the prevalence of obstructive sleep apnea in a group of South American patients with mucopolysaccharidosis type VI who had no previous or current treatment with enzyme replacement or bone marrow transplant. Inclusion criteria were: age 4 years or older; and biochemical confirmation of the disease – reduced arylsulfatase B activity, increased glycosaminoglycans (GAGs) in urine, and normal activity of at least one other sulfatase. Twenty-eight patients were examined and data were collected from clinical history, physical examination, transthoracic Doppler echocardiogram and overnight polysomnography. Of the 28 participants, 14 (50%) were boys; mean age at evaluation was 98.5 months, and mean age at MPS diagnosis, 48.4 months. Symptoms started before 38 months of age in 88% of the sample; 27% reported parental consanguinity. The most frequent clinical symptoms during sleep were snoring and witnessed apnea. Physical examination revealed that 78.6% had macroglossia, and 82.1%, pectus carinatum. The most frequent clinical symptoms during sleep were snoring and witnessed apnea. Physical examination revealed that 78.6% had macroglossia, and 82.1%, pectus carinatum. Three (10.71%) patients had already undergone adenotonsillectomy, and 6 (21.42%), isolated adenoidectomy. Polysomnography results showed that 23 (85.1%) patients had obstructive sleep apnea: 4 mild, 5 moderate, and 14 severe. Mean apnea-hypopnea index (AHI) was 19.84 ± 26.25 events/hour, oxygen saturation (SpO2), 93.25 ± 5.06%, SpO2 nadir, 80.29 ± 10.01%, and peak end-tidal carbon dioxide (EtCO2), 44.1 ± 6.01 mmHg. Central apneas were rare. Pulmonary hypertension (PH) was detected by echocardiography in 14 (50%) patients. Lower SpO2 mean and nadir were positively associated with PH. In the group of patients with PH, SpO2 mean and nadir were 91.2 ± 6.4% and 75.4 ± 10.9%, and in the group without PH, 95.3 ± 1.8% and 85.2 ± 6.1% (p=0.037 for mean; p=0.007 for nadir). Witnessed apneas during sleep were the most important variable to predict PH in this sample (p=0.016; OR 9.9; CI, 1.5 to 63.7). Clinical signs suggestive of respiratory abnormalities during sleep were not significantly correlated with AHI, SpO2 mean and nadir, or peak EtCO2. There was no significant correlation between GAGs in urine or enzyme activity and polysomnography or echocardiogram results. The prevalence of obstructive sleep apnea in patients with mucopolysaccharidosis type VI was high, and the level of desaturation was positively correlated with the presence of pulmonary hypertension. Symptoms observed during sleep were not associated with polysomnography results. Witnessed apneas during the sleep were the most important variable to predict PH.

Introdução: A patogênese da apneia obstrutiva do sono envolve estreitamento da faringe causado por deslocamento de líquido das pernas para o pescoço durante a noite. Objetivo: Determinar o efeito de intervenções que depletem líquido corporal na gravidade da apneia obstrutiva do sono. Métodos: Em ensaio randomizado controlado com placebo, homens diagnosticados com apneia obstrutiva do sono grave, segundo os critérios da Academia Americana de Medicina do Sono, foram aleatoriamente designados para receber diariamente diurético Lasilactona (espironolactona 100 mg + furosemida 20 mg) ou pílula placebo ou aconselhamento nutricional para dieta com restrição de sódio mais pílula placebo. O período de intervenção foi de uma semana. Todos os participantes realizaram a polissonografia portátil tipo III no início e no final do estudo. A mudança no índice de apneia hipopneia (IAH) foi o desfecho primário. Resultados: O estudo incluiu 54 participantes com média de idade (±DP) de 45±8,8 anos, IMC de 29,9±2,9 kg/m2 e IAH de 49±19 eventos/h. A mudança no IAH foi -11 eventos/h de sono (intervalo de confiança de 95% [IC], -15,59 para -5,74) no grupo de dieta, -7,33 (IC 95%, -13,75 para -0,91) no grupo diurético e 0,33 (IC 95%, -2,51 para 3,17) no grupo placebo (P=0,001 para interação tempo × grupo). A redução de água corporal total foi 2,2±2,2 L no grupo diurético (P<0,001) e 1,0±1,6 L no grupo dieta (P=0,002). Os sintomas de sonolência e a circunferência do pescoço reduziram significativamente somente no grupo dieta (P=0,007 e P<0,001 para interação, respectivamente). O uso de diurético aumentou a concentração de aldosterona e a atividade da renina plasmática (P<0,001 para interação). Conclusões: Em homens com apneia obstrutiva do sono grave, intervenções dietéticas e farmacológicas que depletam líquido corporal diminuem o IAH. Esse estudo fornece evidências de que a retenção de líquido corporal desempenha papel na patogênese da apneia do sono. / Rationale: The pathogenesis of obstructive sleep apnea involves pharyngeal narrowing caused by overnight fluid displacement from the legs to the neck. Objective: To determine the effect of interventions that reduced the body fluid content on obstructive sleep apnea severity. Methods: In this placebo-controlled study, men diagnosed with severe obstructive sleep apnea according American Academy of Sleep Medicine clinical criteria were randomized to receive daily diuretic lasilactone (spironolactone 100 mg + furosemide 20 mg) or placebo pill or nutritional counseling to sodium-restricted diet plus placebo pill. The intervention period was one week. All participants underwent out-of-center polysomnographies at baseline and follow-up. The change in apnea-hypopnea index (AHI) was the main outcome. Results: The study included 54 participants with mean age (±SD) of 45±8.8 years, body mass index of 29.9±2.9 kg/m2, and AHI of 49±19 events/h. From baseline to follow-up, the AHI delta value was −11 (95% confidence interval [CI], −15.59 to −5.74) in the diet group, −7.33 (95% CI, −13.75 to −0.91) in the diuretic group, and 0.33 (95% CI, −2.51 to 3.17) in the placebo group (P=0.001 for time × group interaction). The reduction in the total body water was 2.2±2.2 L in the diuretic group (P<0.001) and 1.0±1.6 L in the diet group (P=0.002). Sleepiness and neck circumference reduced only in the diet group (P=0.007 and P<0.001 for the interaction, respectively). The diuretic use augmented aldosterone concentration and plasma renin activity (P<0.001 for the interaction). Conclusions: Among men with severe OSA, dietary and pharmacological interventions that decrease bodily fluid content reduce the AHI. This trial provides a finding that fluid retention plays a role in apnea pathogenesis.

Introdução: O desenvolvimento de hipertensão arterial e doença cardiovascular relacionado à síndrome das apnéia obstrutiva do sono (SAOS) parece estar relacionado a alterações sobre a regulação autonômica cardiovascular. Este estudo investigou se a SAOS influência a variabilidade da pressão arterial (PA). Métodos: Estudo transversal, com pacientes hipertensos que foram submetidos à polissonografia nível III, por meio de um monitor portátil de uso domiciliar para detectar SAOS (índice de apnéia-hipopnéia (IAH) ≥ 10). A variabilidade da PA foi avaliada pela taxa de variação da pressão arterial no tempo (índice “time rate” - a primeira derivada da pressão arterial ao longo do tempo) e desvio padrão (DP) da PA obtidos dos dados da monitorização ambulatorial da pressão arterial (MAPA). Análises univariadas e multivariadas foram utilizadas para testar a associação entre a SAOS, IAH e variabilidade da pressão arterial. Resultados: Os pacientes com SAOS (n = 57) eram mais velhos, apresentavam pressão arterial mais elevada e maior duração da hipertensão do que pacientes sem SAOS (n = 50). Não houve nenhuma associação consistente entre o diagnóstico de SAOS e variabilidade da PA aferida pelo DP e pela taxa de variação da PA no tempo, tanto na análise univariada como após o ajuste para idade, IMC e respectiva medida de PA na MAPA. Não houve correlação significativa entre o AIH e os índices de variabilidade da PA em um modelo de regressão linear múltipla, controlando para idade, IMC e PA correspondente. Conclusão: SAOS não influencou a variabilidade da pressão arterial, aferida por estes métodos, em pacientes com hipertensão. / Background The risk of obstructive sleep apnea syndrome (OSAS) for the development of hypertension and cardiovascular disease may be intermediate by influence over autonomic cardiovascular regulation. This study investigated if OSAS influences blood pressure (BP) variability. Methods In a cross-sectional study, patients with hypertension underwent level III polysomnography by means of a home portable monitor to detect OSAS, (apnea-hypopnea index (AHI) ≥10). BP variability was assessed by the time rate index (the first derivative of BP over time) and standard deviation (SD) of BP measured by 24-h ambulatory blood pressure measurement (ABPM). The association between OSAS, AHI and blood pressure variability was tested by univariate and multivariate methods. Results: Patients with OSAS (n = 57) were older, had higher blood pressure, and longer duration of hypertension than patients without OSAS (n = 50). There was no consistent association between the diagnosis of OSAS and BP variability assessed by the time-rate index and SD both in the univariate and after adjustment for age, BMI and the respective BP. There was no significant correlation between AIH and the indexes of BP variability in a multiple linear regression model controlling for age, BMI and the corresponding BP. Conclusion OSAS does not influence blood pressure variability in patients with hypertension.