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1.
Stroke ; 51(7): 2188-2196, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32513093

RESUMO

BACKGROUND AND PURPOSE: Cardiopulmonary coupling (CPC) analysis is an easily assessable method to evaluate sleep-disordered breathing (SDB); however, its prognostic impact in patients with acute ischemic stroke needs to be investigated. We performed a CPC analysis using Holter monitoring at the early stage of noncardioembolic ischemic stroke to investigate the prognostic effect of SDB on functional impairment at the 3-month follow-up. METHODS: A total 615 patients with acute noncardioembolic ischemic stroke who underwent Holter monitoring within 30 days of stroke onset were enrolled from a multicenter, prospective, all-comer cohort. CPC analysis was conducted, and SDB was defined by the presence of narrow-band coupling during sleep time. We investigated the association between SDB and functional impairment at 3 months as measured by the modified Rankin Scale. RESULT: Narrow-band coupling was present in 191 (31.1%) of 615 patients (mean age 64.5±12.6 years). The narrow-band group showed a significantly higher rate of severe functional impairment (modified Rankin Scale score >2; 45.5% versus 12.9%, P<0.001) and persistent disability (Δmodified Rankin Scale score ≤0; 53.9% versus 39.8%, P<0.001) at the 3-month follow-up. In multivariate analysis, narrow-band coupling was an independent predictor of higher risk of severe and persistent functional impairment at 3 months (odds ratio, 3.98 [95% CI, 2.34-6.78]; P<0.001; and odds ratio, 1.81 [95% CI, 1.23-2.66]; P<0.001, respectively). The results remained consistent after propensity-score matched analysis with 157 patient pairs (C-statistic=0.770). CONCLUSIONS: SDB assessed by CPC analysis at the early stage of ischemic stroke could predict severe and prolonged functional impairment at 3 months. CPC analysis using Holter monitoring can help predicting functional impairment in acute ischemic stroke.


Assuntos
Recuperação de Função Fisiológica/fisiologia , Síndromes da Apneia do Sono/complicações , Acidente Vascular Cerebral/complicações , Idoso , Isquemia Encefálica/complicações , Isquemia Encefálica/fisiopatologia , Eletrocardiografia Ambulatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Síndromes da Apneia do Sono/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia
2.
Pediatr Pulmonol ; 55(8): 1974-1983, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32364318

RESUMO

BACKGROUND: Studies have shown that sleep disorders occur in cystic fibrosis (CF) patients and may be present before daytime clinical manifestations. OBJECTIVES: To evaluate the presence of sleep disorders among children and adolescents with CF, attempting to identify associations with pulmonary function, nutritional status, days in hospital, and days taking antibiotics. METHODS: Individuals with a diagnosis of CF aged between 6 and 18 years were included. Information on sociodemographic, clinical profile, history of hospitalizations, and use of antibiotics in the last year were collected. Spirometry, bioimpedance, and polysomnography were performed. The presence of nocturnal hypoxemia and obstructive sleep apnea syndrome (OSAS) were evaluated and participants divided according to their presence. RESULTS: Thirty-one patients were included. The prevalence of OSAS was 32.3% and nocturnal hypoxemia was 29.0%. Average nocturnal peripheral oxyhemoglobin saturation (SpO2 ) correlated (P < .001) with forced vital capacity (r = .55) and forced expiratory volume in the first second (r = .62). The higher the percentage of total sleep time (TST) with SpO2 less than 90%, the lower the pulmonary function. Individuals with OSAS and nocturnal hypoxemia had lower spirometric values compared to patients without these disorders, but the nocturnal hypoxemia group also had lower Shwachman-Kulczycki score, longer hospitalization time and antibiotic use. TST with SpO2 less than 90% was associated with length of hospitalization (r2 = .53). CONCLUSION: Children and adolescents with CF have sleep disorders, including OSAS (32.3%) and nocturnal hypoxemia (29%). Individuals with nocturnal hypoxemia presented lower lung function, worse clinical score, and higher morbidity. TST with SpO2 less than 90% was associated with length of hospitalization.


Assuntos
Fibrose Cística/fisiopatologia , Hipóxia/fisiopatologia , Síndromes da Apneia do Sono/fisiopatologia , Adolescente , Biomarcadores , Criança , Fibrose Cística/epidemiologia , Feminino , Volume Expiratório Forçado , Humanos , Hipóxia/epidemiologia , Masculino , Morbidade , Estado Nutricional , Polissonografia , Prevalência , Síndromes da Apneia do Sono/epidemiologia , Transtornos do Sono-Vigília , Espirometria , Capacidade Vital
3.
Circ Cardiovasc Imaging ; 13(5): e009074, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32408831

RESUMO

BACKGROUND: Prior studies have found that sleep-disordered breathing (SDB) is common among those with left ventricular (LV) dysfunction and heart failure. Few epidemiological studies have examined this association, especially in US Hispanic/Latinos, who may be at elevated risk of SDB and heart failure. METHODS: We examined associations between SDB and LV diastolic and systolic function using data from 1506 adults aged 18 to 64 years in the Hispanic Community Health Study/Study of Latinos ECHO-SOL Ancillary Study (2011-2014). Home sleep testing was used to measure the apnea-hypopnea index, a measure of SDB severity. Echocardiography was performed a median of 2.1 years later to quantify LV diastolic function, systolic function, and structure. Multivariable linear regression was used to model the association between apnea-hypopnea index and echocardiographic measures while accounting for the complex survey design, demographics, body mass, and time between sleep and echocardiographic measurements. RESULTS: Each 10-unit increase in apnea-hypopnea index was associated with 0.2 (95% CI, 0.1-0.3) lower E', 0.3 (0.1-0.5) greater E/E' ratio, and 1.07-fold (1.03-1.11) higher prevalence of diastolic dysfunction as well as 1.3 (0.3-2.4) g/m2 greater LV mass index. These associations persisted after adjustment for hypertension and diabetes mellitus. In contrast, no association was identified between SDB severity and subclinical markers of LV systolic function. CONCLUSIONS: Greater SDB severity was associated with LV hypertrophy and subclinical markers of LV diastolic dysfunction. These findings suggest SDB in Hispanic/Latino men and women may contribute to the burden of heart failure in this population.


Assuntos
Insuficiência Cardíaca/fisiopatologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Síndromes da Apneia do Sono/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda , Remodelação Ventricular , Adolescente , Adulto , Idoso , Estudos Transversais , Diástole , Ecocardiografia , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/etnologia , Hispano-Americanos , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/etnologia , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Prospectivos , Fatores Raciais , Respiração , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Sono , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/etnologia , Estados Unidos/epidemiologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etnologia , Adulto Jovem
5.
PLoS One ; 15(4): e0232287, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32339208

RESUMO

OBJECTIVE: Sleep-disordered breathing (SDB) is characterised by intermittent hypoxemia, sympathetic activation and widespread endothelial dysfunction, sharing pathophysiologic features with the hypertensive disorders of pregnancy. We sought to determine whether coexisting SDB would adversely impact the outcomes of women with gestational hypertension (GH) and preeclampsia (PE), and healthy matched controls. STUDY DESIGN: Women diagnosed with GH or PE along with BMI- and gestation-matched normotensive controls underwent polysomnography in late pregnancy to establish the presence or absence of SDB (RDI ≥ 5). Clinical outcomes of hypertensive disease severity were compared between groups, and venous blood samples were taken in the third trimester and at delivery to examine for any impact of SDB on the anti-angiogenic markers of PE. RESULTS: Data was available for 17 women with PE, 24 women with GH and 44 controls. SDB was diagnosed in 41% of the PE group, 63% of the GH group and 39% of the control group. Women with PE and co-existing SDB did not have worse outcomes in terms of gestation at diagnosis of PE (SDB = 29.1 (25.9, 32.1) weeks vs. no SDB = 32.0 (29.0, 33.9), p = n.s.) and days between diagnosis of PE and delivery (SDB = 20.0 (4.0, 35.0) days vs. no SDB = 10.5 (9.0, 14.0), p = n.s.). There were also no differences in severity of hypertension, antihypertensive treatment and biochemical, haematological and anti-angiogenic markers of PE between SDB and no SDB groups. Similar results were observed among women with GH. Healthy control women with SDB were no more likely to develop a hypertensive disorder of pregnancy in the later stages of pregnancy (SDB = 5.9% vs. no SDB = 7.4%, p = n.s.). Increasing the threshold for diagnosis of SDB to RDI ≥ 15 did not unmask a worse prognosis. CONCLUSION: The presence of SDB during pregnancy did not worsen the disease course of GH or PE, and was not associated with high blood pressure or anti-angiogenic markers of hypertensive disease amongst healthy pregnant women. Given the numerous reports of the relationship between SDB and diagnosis of hypertensive disorders of pregnancy, it appears more work is required to distinguish causal, versus confounding, pathways.


Assuntos
Hipertensão Induzida pela Gravidez/etiologia , Hipertensão Induzida pela Gravidez/fisiopatologia , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/fisiopatologia , Adulto , Anti-Hipertensivos/uso terapêutico , Feminino , Humanos , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Hipertensão Induzida pela Gravidez/metabolismo , Fator de Crescimento Placentário/metabolismo , Polissonografia/métodos , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/fisiopatologia , Gravidez , Fatores de Risco , Síndromes da Apneia do Sono/metabolismo
6.
Pediatr Pulmonol ; 55(6): 1495-1502, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32289209

RESUMO

BACKGROUND: To date there are limited data in the literature to guide the initial evaluation for etiologies of apnea in full-term infants born at greater than or equal to 37 weeks conceptional age (apnea of infancy [AOI]). Pediatricians and pediatric pulmonologists are left to pursue a broad, rather than targeted and a stepwise approach to begin diagnostic evaluation. METHODS: We performed a retrospective chart review of 101 symptomatic full-term infants (age under 12 months) diagnosed with apnea with an inpatient multichannel pneumogram (six channels) or a fully attended overnight pediatric polysomnogram in our outpatient sleep center accredited by American Academy of Sleep Medicine (AASM), scored using the standards set forth by the AASM. The infant was diagnosed as having AOI if the apnea hypopnea index (AHI) was greater than 1 (AHI is defined as the number of apnea and hypopnea events per hour of sleep). The final diagnosis/etiology was determined based on physician clinical assessment and work up. We then determined the frequency for each diagnosis. RESULTS: We found that the three most common etiologies were gastroesophageal reflux disease (GERD) (48/101), upper airway abnormalities/obstruction (37/101), and neurological diseases (19/101). There were significant numbers of infants with multiple etiologies for AOI. CONCLUSION: Based on the frequencies obtained, pediatric practitioners caring for full-term infants with apnea of unknown etiology are advised to begin with evaluation of more likely causes such as GERD and upper airway abnormalities/obstruction before evaluating for less common causes.


Assuntos
Refluxo Gastroesofágico/complicações , Doenças do Sistema Nervoso/complicações , Anormalidades do Sistema Respiratório/complicações , Síndromes da Apneia do Sono/etiologia , Feminino , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/fisiopatologia , Humanos , Lactente , Recém-Nascido , Masculino , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/fisiopatologia , Polissonografia , Anormalidades do Sistema Respiratório/diagnóstico , Anormalidades do Sistema Respiratório/fisiopatologia , Estudos Retrospectivos , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/fisiopatologia
7.
Proc Natl Acad Sci U S A ; 117(15): 8624-8632, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32229567

RESUMO

Cortical arousal from sleep is associated with autonomic activation and acute increases in heart rate. Arousals vary considerably in their frequency, intensity/duration, and physiological effects. Sleep and arousability impact health acutely (daytime cognitive function) and long-term (cardiovascular outcomes). Yet factors that modify the arousal intensity and autonomic activity remain enigmatic. In this study of healthy human adults, we examined whether reflex airway defense mechanisms, specifically swallowing or glottic adduction, influenced cardiac autonomic activity and cortical arousal from sleep. We found, in all subjects, that swallows trigger rapid, robust, and patterned tachycardia conserved across wake, sleep, and arousal states. Tachycardia onset was temporally matched to glottic adduction-the first phase of swallow motor program. Multiple swallows increase the magnitude of tachycardia via temporal summation, and blood pressure increases as a function of the degree of tachycardia. During sleep, swallows were overwhelmingly associated with arousal. Critically, swallows were causally linked to the intense, prolonged cortical arousals and marked tachycardia. Arousal duration and tachycardia increased in parallel as a function of swallow incidence. Our findings suggest that cortical feedback and tachycardia are integrated responses of the swallow motor program. Our work highlights the functional influence of episodic, involuntary airway defense reflexes on sleep and vigilance and cardiovascular function in healthy individuals.


Assuntos
Nível de Alerta/fisiologia , Ritmo Circadiano/fisiologia , Deglutição/fisiologia , Síndromes da Apneia do Sono/fisiopatologia , Taquicardia/fisiopatologia , Adolescente , Adulto , Idoso , Pressão Sanguínea , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Sensors (Basel) ; 20(5)2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32121672

RESUMO

This paper is devoted to proving two goals, to show that various depth sensors can be used to record breathing rate with the same accuracy as contact sensors used in polysomnography (PSG), in addition to proving that breathing signals from depth sensors have the same sensitivity to breathing changes as in PSG records. The breathing signal from depth sensors can be used for classification of sleep [d=R2]apneaapnoa events with the same success rate as with PSG data. The recent development of computational technologies has led to a big leap in the usability of range imaging sensors. New depth sensors are smaller, have a higher sampling rate, with better resolution, and have bigger precision. They are widely used for computer vision in robotics, but they can be used as non-contact and non-invasive systems for monitoring breathing and its features. The breathing rate can be easily represented as the frequency of a recorded signal. All tested depth sensors (MS Kinect v2, RealSense SR300, R200, D415 and D435) are capable of recording depth data with enough precision in depth sensing and sampling frequency in time (20-35 frames per second (FPS)) to capture breathing rate. The spectral analysis shows a breathing rate between 0.2 Hz and 0.33 Hz, which corresponds to the breathing rate of an adult person during sleep. To test the quality of breathing signal processed by the proposed workflow, a neural network classifier (simple competitive NN) was trained on a set of 57 whole night polysomnographic records with a classification of sleep [d=R2]apneaapnoas by a sleep specialist. The resulting classifier can mark all [d=R2]apneaapnoa events with 100% accuracy when compared to the classification of a sleep specialist, which is useful to estimate the number of events per hour. [d=R2]When compared to the classification of polysomnographic breathing signal segments by a sleep specialistand, which is used for calculating length of the event, the classifier has an [d=R1] F 1 score of 92.2%Accuracy of 96.8% (sensitivity 89.1% and specificity 98.8%). The classifier also proves successful when tested on breathing signals from MS Kinect v2 and RealSense R200 with simulated sleep [d=R2]apneaapnoa events. The whole process can be fully automatic after implementation of automatic chest area segmentation of depth data.


Assuntos
Síndromes da Apneia do Sono/fisiopatologia , Sono/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia/métodos , Respiração , Taxa Respiratória/fisiologia , Sensibilidade e Especificidade , Processamento de Sinais Assistido por Computador
9.
BMC Cardiovasc Disord ; 20(1): 118, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32138679

RESUMO

BACKGROUND: Sleep apnea and diabetes mellitus (DM) negatively impact cardiovascular health. One important indicator of cardiovascular health is the Ankle-Brachial Index (ABI). Either low ABI or high ABI are signs of peripheral vascular impairment. Impaired vascular health and DM, together, might provoke sleep apnea; however, information regarding these relationships is limited. Therefore, this study aimed to investigate the association between ABI, DM status, and severity of obstructive sleep apnea in people of Hispanic/Latino descent who are diverse in culture, environmental exposures, nativity, socioeconomic status, and disease burden. METHODS: A cross sectional analysis from a multi-center epidemiologic study, Hispanic Community Health Study/Study of Latinos, was utilized and included 3779 participants (mean age 55.32 ± 7.67, females 57.9%). The sample was divided into 4 groups based on the American Diabetes Association diagnostic guidelines (no DM or DM), and the ABI status (normal and abnormal). Multiple linear regression analysis was used to determine the association of the four groups and other independent variables with severity of sleep apnea measured by apnea-hypopnea index. Kruskal-Wallis H test was used for comparisons between groups for the apnea-hypopnea index. The significant level was set at 0.01. RESULTS: There were significant differences between groups in the mean of apnea-hypopnea index (P < 0.001; no DM + normal ABI = 5.42 ± 9.66, no DM + abnormal ABI = 7.11 ± 11.63, DM + normal ABI = 10.99 ± 15.16, DM + abnormal ABI = 12.81 ± 17.80). Linear regression showed that DM and abnormal ABI were significantly associated with severe sleep apnea (ß = 3.25, P = 0.001) after controlling for age, sex, BMI, income, education, alcohol use, cigarette use, hypertension or related medication, stroke and statin use. CONCLUSION: These findings suggest that people with DM and abnormal ABI were more likely to have high apnea-hypopnea index compared to the other groups. We observed gradual increasing in the severity of sleep apnea from low abnormality groups to high abnormality groups for Hispanic/Latino. Further work should elucidate the association of DM, abnormal ABI and sleep apnea with longer term outcomes, and replicate this work in different populations.


Assuntos
Índice Tornozelo-Braço , Doenças Cardiovasculares/etnologia , Diabetes Mellitus/etnologia , Hispano-Americanos , Síndromes da Apneia do Sono/etnologia , Adolescente , Adulto , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Estudos Transversais , Bases de Dados Factuais , Diabetes Mellitus/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Índice de Gravidade de Doença , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/fisiopatologia , Estados Unidos/epidemiologia , Adulto Jovem
10.
Curr Hypertens Rep ; 22(4): 28, 2020 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-32166454

RESUMO

PURPOSE OF REVIEW: Pathophysiology of hypertensive disorders of pregnancy (HDP), especially preeclampsia, has not been fully elucidated. Most trials aimed at the prevention of preeclampsia have failed to show significant benefit and investigation of novel, modifiable risk factors is sorely needed. Sleep disordered breathing (SDB), a group of disorders for which treatments are available, meets these criteria. SDB impacts about a third of all pregnancies and is associated with hypertension in the general non-pregnant population. RECENT FINDINGS: Recent studies have shown a high prevalence of SDB, especially in complicated pregnancies. Several studies have shown that pregnant women with SDB have a higher risk for developing HDP, and these two disorders are associated with similar maternal long-term cardiovascular outcomes. Based on limited animal models of gestational intermittent hypoxia and human studies, SDB and HDP share similar risk factors and some pathophysiological mechanisms. However, there is paucity of studies addressing causality of this association and identifying therapeutic targets for intervention. Maternal SDB represents a novel and modifiable risk factor of HDP. Further studies are needed in order to establish the exact mechanisms underlying this association and to identify specific areas for clinical interventions.


Assuntos
Hipertensão Induzida pela Gravidez/etiologia , Síndromes da Apneia do Sono/complicações , Feminino , Humanos , Hipertensão Induzida pela Gravidez/fisiopatologia , Hipertensão Induzida pela Gravidez/prevenção & controle , Hipertensão Induzida pela Gravidez/terapia , Placenta/fisiopatologia , Polissonografia , Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/fisiopatologia , Pré-Eclâmpsia/prevenção & controle , Pré-Eclâmpsia/terapia , Gravidez , Fatores de Risco , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/fisiopatologia , Síndromes da Apneia do Sono/terapia
12.
J Craniofac Surg ; 31(3): 720-726, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32049904

RESUMO

Children with cleft and craniofacial conditions commonly present with concurrent airway anomalies, which often manifest as sleep disordered breathing. Craniofacial surgeons and members of the multidisciplinary team involved in the care of these patients should appreciate and understand the scope of airway pathology as well as the proper means of airway assessment. This review article details the prevalence and assessment of sleep disordered breathing in patients with craniofacial anomalies, with emphasis on indications, limitations, and interpretation of polysomnography.


Assuntos
Síndromes da Apneia do Sono/fisiopatologia , Criança , Anormalidades Craniofaciais/complicações , Humanos , Polissonografia , Prevalência , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/etiologia
13.
Am J Respir Cell Mol Biol ; 62(6): 732-746, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32048876

RESUMO

Pulmonary vasoconstriction resulting from intermittent hypoxia (IH) contributes to pulmonary hypertension (pHTN) in patients with sleep apnea (SA), although the mechanisms involved remain poorly understood. Based on prior studies in patients with SA and animal models of SA, the objective of this study was to evaluate the role of PKCß and mitochondrial reactive oxygen species (mitoROS) in mediating enhanced pulmonary vasoconstrictor reactivity after IH. We hypothesized that PKCß mediates vasoconstriction through interaction with the scaffolding protein PICK1 (protein interacting with C kinase 1), activation of mitochondrial ATP-sensitive potassium channels (mitoKATP), and stimulated production of mitoROS. We further hypothesized that this signaling axis mediates enhanced vasoconstriction and pHTN after IH. Rats were exposed to IH or sham conditions (7 h/d, 4 wk). Chronic oral administration of the antioxidant Tempol or the PKCß inhibitor LY-333531 abolished IH-induced increases in right ventricular systolic pressure and right ventricular hypertrophy. Furthermore, scavengers of O2- or mitoROS prevented enhanced PKCß-dependent vasoconstrictor reactivity to endothelin-1 in pulmonary arteries from IH rats. In addition, this PKCß/mitoROS signaling pathway could be stimulated by the PKC activator PMA in pulmonary arteries from control rats, and in both rat and human pulmonary arterial smooth muscle cells. These responses to PMA were attenuated by inhibition of mitoKATP or PICK1. Subcellular fractionation and proximity ligation assays further demonstrated that PKCß acutely translocates to mitochondria upon stimulation and associates with PICK1. We conclude that a PKCß/mitoROS signaling axis contributes to enhanced vasoconstriction and pHTN after IH. Furthermore, PKCß mediates pulmonary vasoconstriction through interaction with PICK1, activation of mitoKATP, and subsequent mitoROS generation.


Assuntos
Hipertensão Pulmonar/fisiopatologia , Hipóxia/fisiopatologia , Mitocôndrias/fisiologia , Proteína Quinase C beta/fisiologia , Artéria Pulmonar/fisiopatologia , Vasoconstrição/fisiologia , Animais , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/metabolismo , Células Cultivadas , Óxidos N-Cíclicos/farmacologia , Proteínas do Citoesqueleto/antagonistas & inibidores , Proteínas do Citoesqueleto/metabolismo , Depuradores de Radicais Livres/farmacologia , Humanos , Hipertensão Pulmonar/etiologia , Hipóxia/complicações , Hipóxia/enzimologia , Indóis/farmacologia , Masculino , Maleimidas/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiopatologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/enzimologia , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/metabolismo , Canais de Potássio/metabolismo , Mapeamento de Interação de Proteínas , Artéria Pulmonar/enzimologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Síndromes da Apneia do Sono/fisiopatologia , Marcadores de Spin , Acetato de Tetradecanoilforbol/farmacologia
14.
Nutr Metab Cardiovasc Dis ; 30(4): 683-693, 2020 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-32008915

RESUMO

BACKGROUND AND AIMS: Pediatric obesity and sleep-disordered breathing (SDB) are associated with cardiometabolic risk (CMR), but the degree of severity at which SDB affects cardiometabolic health is unknown. We assessed the relationship between the CMR and the apnea-hypopnea index (AHI), to identify a threshold of AHI from which an increase in the CMR is observed, in adolescents with obesity. We also compared the clinical, cardiometabolic and sleep characteristics between adolescents presenting a high (CMR+) and low CMR (CMR-), according to the threshold of AHI. METHODS AND RESULTS: 114 adolescents with obesity were recruited from three institutions specialized in obesity management. Sleep and SDB as assessed by polysomnography, anthropometric parameters, fat mass (FM), glucose and lipid profiles, and blood pressure (BP) were measured at admission. Continuous (MetScoreFM) and dichotomous (metabolic syndrome, MetS) CMR were determined. Associations between MetScoreFM and AHI adjusted for BMI, sex and age were assessed by multivariable analyses. Data of 82 adolescents were analyzed. Multivariable analyses enabled us to identify a threshold of AHI = 2 above which we observed a strong and significant association between CMR and AHI (Cohen's d effect-size = 0.57 [0.11; 1.02] p = 0.02). Adolescents with CMR+ exhibited higher MetScoreFM (p < 0.05), insulin resistance (p < 0.05), systolic BP (p < 0.001), sleep fragmentation (p < 0.01) and intermittent hypoxia than CMR- group (p < 0.0001). MetS was found in 90.9% of adolescents with CMR+, versus 69.4% in the CMR- group (p < 0.05). CONCLUSIONS: The identification of a threshold of AHI ≥ 2 corresponding to the cardiometabolic alterations highlights the need for the early management of SDB and obesity in adolescents, to prevent cardiometabolic diseases. CLINICAL TRIALS: NCT03466359, NCT02588469 and NCT01358773.


Assuntos
Metabolismo Energético , Pulmão/fisiopatologia , Síndrome Metabólica/etiologia , Obesidade Pediátrica/complicações , Respiração , Síndromes da Apneia do Sono/etiologia , Sono , Adiposidade , Adolescente , Fatores Etários , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea , Brasil , Feminino , França , Humanos , Resistência à Insulina , Lipídeos/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/fisiopatologia , Obesidade Pediátrica/sangue , Obesidade Pediátrica/diagnóstico , Obesidade Pediátrica/fisiopatologia , Medição de Risco , Fatores de Risco , Síndromes da Apneia do Sono/sangue , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/fisiopatologia
15.
PLoS One ; 15(2): e0229568, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32101584

RESUMO

OBJECTIVE: To determine whether the presence of co-existing sleep-disordered breathing (SDB) is associated with worse perinatal outcomes among women diagnosed with a hypertensive disorder of pregnancy (HDP), compared with normotensive controls. STUDY DESIGN: Women diagnosed with HDP (gestational hypertension or preeclampsia) and BMI- and gestation-matched controls underwent polysomnography in late pregnancy to determine if they had coexisting SDB. Fetal heart rate (FHR) monitoring accompanied the sleep study, and third trimester fetal growth velocity was assessed using ultrasound. Cord blood was taken at delivery to measure key regulators of fetal growth. RESULTS: SDB was diagnosed in 52.5% of the HDP group (n = 40) and 38.1% of the control group (n = 42); p = .19. FHR decelerations were commonly observed during sleep, but the presence of SDB did not increase this risk in either the HDP or control group (HDP group-SDB = 35.3% vs. No SDB = 40.0%, p = 1.0; control group-SDB = 41.7% vs. No SDB = 25.0%, p = .44), nor did SDB affect the total number of decelerations overnight (HDP group-SDB = 2.7 ± 1.0 vs. No SDB = 2.8 ± 2.1, p = .94; control group-SDB = 2.0 ± 0.8 vs. No SDB = 2.0 ± 0.7, p = 1.0). Fetal growth restriction was the strongest predictor of fetal heart rate events during sleep (aOR 5.31 (95% CI 1.26-22.26), p = .02). The presence of SDB also did not adversely affect fetal growth; in fact among women with HDP, SDB was associated with significantly larger customised birthweight centiles (43.2% ± 38.3 vs. 16.2% ± 27.0, p = .015) and fewer growth restricted babies at birth (30% vs. 68.4%, p = .026) compared to HDP women without SDB. There was no impact of SDB on measures of fetal growth for the control group. Cord blood measures of fetal growth did not show any adverse effect among women with SDB, either in the HDP or control group. CONCLUSION: We did not find that the presence of mild SDB worsened fetal acute or longitudinal outcomes, either among women with HDP or BMI-matched normotensive controls. Unexpectedly, we found the presence of SDB conferred a better prognosis in HDP in terms of fetal growth. The fetus has considerable adaptive capacity to withstand in utero hypoxia, which may explain our mostly negative findings. In addition, SDB in this cohort was mostly mild. It may be that fetal sequelae will only be unmasked in the setting of more severe degrees of SDB and/or underlying placental disease.


Assuntos
Hipertensão Induzida pela Gravidez/fisiopatologia , Resultado da Gravidez/epidemiologia , Síndromes da Apneia do Sono/fisiopatologia , Adulto , Austrália , Peso ao Nascer , Estudos de Coortes , Feminino , Desenvolvimento Fetal/fisiologia , Retardo do Crescimento Fetal/metabolismo , Frequência Cardíaca Fetal/fisiologia , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/metabolismo , Recém-Nascido Pequeno para a Idade Gestacional/fisiologia , Parto/fisiologia , Polissonografia , Pré-Eclâmpsia/fisiopatologia , Gravidez , Complicações na Gravidez/fisiopatologia , Terceiro Trimestre da Gravidez , Estudos Prospectivos , Síndromes da Apneia do Sono/complicações
16.
Circ Res ; 126(5): 603-615, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-31902278

RESUMO

RATIONALE: Sleep-disordered breathing (SDB) is frequently associated with atrial arrhythmias. Increased CaMKII (Ca/calmodulin-dependent protein kinase II) activity has been previously implicated in atrial arrhythmogenesis. OBJECTIVE: We hypothesized that CaMKII-dependent dysregulation of Na current (INa) may contribute to atrial proarrhythmic activity in patients with SDB. METHODS AND RESULTS: We prospectively enrolled 113 patients undergoing elective coronary artery bypass grafting for cross-sectional study and collected right atrial appendage biopsies. The presence of SDB (defined as apnea-hypopnea index ≥15/h) was assessed with a portable SDB monitor the night before surgery. Compared with 56 patients without SDB, patients with SDB (57) showed a significantly increased level of activated CaMKII. Patch clamp was used to measure INa. There was a significantly enhanced late INa, but reduced peak INa due to enhanced steady-state inactivation in atrial myocytes of patients with SDB consistent with significantly increased CaMKII-dependent cardiac Na channel phosphorylation (NaV1.5, at serine 571, Western blotting). These gating changes could be fully reversed by acute CaMKII inhibition (AIP [autocamtide-2 related inhibitory peptide]). As a consequence, we observed significantly more cellular afterdepolarizations and more severe premature atrial contractions in atrial trabeculae of patients with SDB, which could be blocked by either AIP or KN93 (N-[2-[[[(E)-3-(4-chlorophenyl)prop-2-enyl]-methylamino]methyl]phenyl]-N-(2-hydroxyethyl)-4-methoxybenzenesulfonamide). In multivariable linear regression models incorporating age, sex, body mass index, existing atrial fibrillation, existing heart failure, diabetes mellitus, and creatinine levels, apnea-hypopnea index was independently associated with increased CaMKII activity, enhanced late INa and correlated with premature atrial contraction severity. CONCLUSIONS: In atrial myocardium of patients with SDB, increased CaMKII-dependent phosphorylation of NaV1.5 results in dysregulation of INa with proarrhythmic activity that was independent from preexisting comorbidities. Inhibition of CaMKII may be useful for prevention or treatment of arrhythmias in SDB. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02877745. Visual Overview: An online visual overview is available for this article.


Assuntos
Arritmias Cardíacas/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Síndromes da Apneia do Sono/metabolismo , Potenciais de Ação , Idoso , Arritmias Cardíacas/complicações , Arritmias Cardíacas/fisiopatologia , Apêndice Atrial/efeitos dos fármacos , Apêndice Atrial/metabolismo , Apêndice Atrial/fisiopatologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/antagonistas & inibidores , Células Cultivadas , Feminino , Humanos , Ativação do Canal Iônico , Masculino , Pessoa de Meia-Idade , Peptídeos/farmacologia , Fosforilação , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/fisiopatologia
17.
J Pediatr ; 218: 92-97, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31952850

RESUMO

OBJECTIVES: To assess clinically asymptomatic infants with single-ventricle physiology (SVP) for sleep-disordered breathing (SDB) in the supine and car seat positions using polysomnography. Polysomnography results also were compared with results of a standard Car Seat Challenge to measure the dependability of the standard Car Seat Challenge. STUDY DESIGN: This was an observational study of 15 infants with SVP. Polysomnography data included Obstructive Index, Central Index, Arousal Index, Apnea Hypopnea Index, and sleep efficiency. Polysomnography heart rate and oxygen saturation data were used to compare polysomnography with the standard Car Seat Challenge. RESULTS: Polysomnography demonstrated that all 15 infants had SDB and 14 had obstructive sleep apnea (Obstructive Index ≥1/hour) in both the supine and car seat positions. Infants with SVP had a statistically significant greater median Obstructive Index in the car seat compared with supine position (6.3 vs 4.2; P = .03), and median spontaneous Arousal Index was greater in the supine position compared with the car seat (20.4 vs 15.2; P = .01). Comparison of polysomnography to standard Car Seat Challenge results demonstrated 5 of 15 (33%) of infants with SVP with abnormal Obstructive Index by polysomnography would have passed a standard Car Seat Challenge. CONCLUSIONS: Infants with SVP without clinical symptoms of SDB may be at high risk for SDB that appears worse in the car seat position. The standard Car Seat Challenge is not dependable in the identification of infants with SVP and SDB. Further studies are warranted to further delineate its potential impact of SDB on the clinical outcomes of infants with SVP.


Assuntos
Doenças Assintomáticas , Cardiopatias Congênitas/fisiopatologia , Frequência Cardíaca/fisiologia , Ventrículos do Coração/anormalidades , Síndromes da Apneia do Sono/fisiopatologia , Feminino , Seguimentos , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , Humanos , Recém-Nascido , Masculino , Consumo de Oxigênio , Polissonografia , Estudos Prospectivos , Índice de Gravidade de Doença , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/diagnóstico
18.
Sensors (Basel) ; 20(1)2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31947905

RESUMO

Sleep apnea (SA) is a prevalent disorder diagnosed by polysomnography (PSG) based on the number of apnea-hypopnea events per hour of sleep (apnea-hypopnea index, AHI). PSG is expensive and technically complex; therefore, its use is rather limited to the initial diagnostic phase and simpler devices are required for long-term follow-up. The validity of single-parameter wearable devices for the assessment of sleep apnea severity is still debated. In this context, a wearable electrocardiogram (ECG) acquisition system (ECG belt) was developed and its suitability for the classification of sleep apnea severity was investigated using heart rate variability analysis with or without data pre-filtering. Several classification algorithms were compared and support vector machine was preferred due to its simplicity and overall performance. Whole-night ECG signals from 241 patients with a suspicion of sleep apnea were recorded using both the ECG belt and patched ECG during PSG recordings. 65% of patients had an obstructive sleep apnea and the median AHI was 21 [IQR: 7-40] h - 1 . The classification accuracy obtained from the ECG belt (accuracy: 72%, sensitivity: 70%, specificity: 74%) was comparable to the patched ECG (accuracy: 74%, sensitivity: 88%, specificity: 61%). The highest classification accuracy was obtained for the discrimination between individuals with no or mild SA vs. moderate to severe SA. In conclusion, the ECG belt provided signals comparable to patched ECG and could be used for the assessment of sleep apnea severity, especially during follow-up.


Assuntos
Técnicas Biossensoriais , Eletrocardiografia , Monitorização Fisiológica/métodos , Síndromes da Apneia do Sono/fisiopatologia , Adulto , Algoritmos , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia/métodos , Índice de Gravidade de Doença , Síndromes da Apneia do Sono/classificação , Síndromes da Apneia do Sono/diagnóstico , Máquina de Vetores de Suporte , Dispositivos Eletrônicos Vestíveis
19.
Heart Fail Clin ; 16(1): 45-51, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31735314

RESUMO

Sleep-disordered breathing (SDB), including obstructive sleep apnea, central sleep apnea (CSA), and Cheyne-Stokes respiration, is common in patients with heart failure (HF) and associated with lower left ventricular ejection fraction (EF), increased arrhythmia burden, and increased mortality. Continuous positive airway pressure therapy improves short-term and long-term outcomes in HF patients. Adaptive servoventilation (ASV) therapy in patients with low-EF HF with predominant CSA is not recommended. Ongoing trials are evaluating whether ASV will have a role in SDB treatment. Phrenic nerve stimulation is an emerging treatment option that has shown promising outcomes. All HF patients should be screened for SDB.


Assuntos
Insuficiência Cardíaca/complicações , Síndromes da Apneia do Sono/etiologia , Sono/fisiologia , Função Ventricular Esquerda/fisiologia , Saúde Global , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Incidência , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/fisiopatologia , Taxa de Sobrevida/tendências
20.
J Stroke Cerebrovasc Dis ; 29(2): 104510, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31767524

RESUMO

BACKGROUND AND PURPOSE: Evidence of an association between sleep apnea (SA) and early neurological deterioration (END) in acute phase ischemic stroke is scant. We investigated the prevalence of SA and the impact of SA severity on END in acute ischemic stroke (AIS) patients. METHODS: We prospectively enrolled consecutive AIS patients admitted to our stroke unit within 72 hours of symptom onset. SA severity was assessed with ApneaLink-a validated portable respiratory monitor. SA was defined as an apnea-hypopnea index (AHI) of greater than or equal to 5 per hour. END was defined as an incremental increase in the National Institutes of Health Stroke Scale (NIHSS) score by greater than or equal to 1 point in motor power, or greater than or equal to 2 points in the total score within the first week after admission. RESULTS: Of the 305 patients studied, 254 (83.3%) patients had SA (AHI ≥ 5 per hour), and of these, 114 (37.4%) had mild SA (AHI 5-14 per hour), 59 (19.3%) had moderate SA (AHI 15-29 per hour), and 81 (26.6%) had severe SA (AHI ≥ 30 per hour). Thirty-six (11.8%) patients experienced END: 2 of the 51 (3.9%) patients without SA and 34 of the 254 (14.4%) patients with SA. Multivariable regression analysis showed AHI independently predicted END (odds ratio 1.024; 95% confidence interval 1.006 to 1.042; P = .008). CONCLUSIONS: SA is common in the acute phase of ischemic stroke, and SA severity is associated with the risk of END.


Assuntos
Isquemia Encefálica/fisiopatologia , Síndromes da Apneia do Sono/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Idoso , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiologia , Avaliação da Deficiência , Progressão da Doença , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , República da Coreia/epidemiologia , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/epidemiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo
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