The nucleus of the solitary tract and the coordination of respiratory and sympathetic activities

It is well known that breathing introduces rhythmical oscillations in the heart rate and arterial pressure levels. Sympathetic oscillations coupled to the respiratory activity have been suggested as an important homeostatic mechanism optimizing tissue perfusion and blood gas uptake/delivery. This respiratory-sympathetic coupling is strengthened in conditions of blood gas challenges (hypoxia and hypercapnia) as a result of the synchronized activation of brainstem respiratory and sympathetic neurons, culminating with the emergence of entrained cardiovascular and respiratory reflex responses. Studies have proposed that the ventrolateral region of the medulla oblongata is a major site of synaptic interaction between respiratory and sympathetic neurons. However, other brainstem regions also play a relevant role in the patterning of respiratory and sympathetic motor outputs. Recent findings suggest that the neurons of the nucleus of the solitary tract (NTS), in the dorsal medulla, are essential for the processing and coordination of respiratory and sympathetic responses to hypoxia. The NTS is the first synaptic station of the cardiorespiratory afferent inputs, including peripheral chemoreceptors, baroreceptors and pulmonary stretch receptors. The synaptic profile of the NTS neurons receiving the excitatory drive from afferent inputs is complex and involves distinct neurotransmitters, including glutamate, ATP and acetylcholine. In the present review we discuss the role of the NTS circuitry in coordinating sympathetic and respiratory reflex responses. We also analyze the neuroplasticity of NTS neurons and their contribution for the development of cardiorespiratory dysfunctions, as observed in neurogenic hypertension, obstructive sleep apnea and metabolic disorders.

Estudo randonizado duplo-cego da capacidade funcional e da prática de atividade física em indivíduos com diagnóstico polissonográfico de SAOS antes e após uso de CPAP

Pós-graduação em Bases Gerais da Cirurgia - FMB

Perfil clínico de crianças com indicação da cirurgia das tonsilas em um hospital terciário universitário

The indications for adenotonsillectomy in pediatric patients have changed considerably during the 90th decade. Local or systemic complications of the adenoid or tonsil hypertrophy itself have now been substituted by signs of obstructive ventilatory disturbances, including obstructive sleep apnea as the major indications for surgery. Objective: This study analyses the clinical profile of children submitted to adenotonsilectomy in their pre and postoperative state, at Botucatu Medical School-State University São Paulo, UNESP. Methods: 332 children of both genders, aged 1 to 12 years, who underwent adenotonsillectomy between 1999 and 2004, were studied, focused on epidemiological profile, pre and postoperative (1 month) symptoms, obtained from medical records. Height and weight were compared to brazilian normal age related values. Results: We found a predominance of the male gender, except in he group aged from 10 to 12 years. Considering wheight and height, we found important failure to thrive, mostly for height deficit. Among clinical aspects, we found a significant reduction in obstructive symptoms like snoring or apneia (p<0001) in the postoperative period. Conclusion: Our results were similar to the literature findings of patients clinical profile. The major indication for adenotonsillectomy in our service was clinical diagnosis of obstructive sleep apnea.

Disturbios neuropsicológicos e síndrome da apneia do sono em crianças

Obstructive Sleep Apnea Syndrome (OSAS) is characterized by snoring and / or repetitive pauses in breathing during sleep associated with hypoxemia and hypercapnia. Affects approximately 1-3% of children, especially preschoolers. There is an association of OSAS with negative impact on neurocognitive development. However, there are few studies using protocols to assess cognition and behavioral disorders in children with OSAS. The objective of this study was to analyze the major studies related to the topic within the last two decades. The main studies published between 1995 to 2011 were identified through MEDLINE and LILACS databases. We selected the most relevant for OSAS in children, neurocognitive effects and association between obstructive disorders / OSAS in the target population (children). It was concluded that the studies analyzed showed that there is strong evidence regarding the overlapping of OSAS in children with neurocognitive disorders and that treatment of OSAS has positive impact on neurocognitive development.

O tratamento da apneia obstrutiva do sono e a utilização de implantes osseointegráveis: revisão da literatura

The obstructive sleep apnea syndrome affects millions of people around the world. The mandibular repositioning devices have been indicated in cases of mild/moderate syndrome; however in edentulous patients its use is deficient since there is no retention. Therefore the objective of this study was to conduct a review on the use of this treatment method combined to osseointegrated implants. A search on the theme: Dental implant and sleep apnea syndromewas performed in the Medline/PubMed, ISI, Cochrane, Dentistry Oral Science, Clinical Trials, Controlled Trials, and Bireme-BvS, databases, and 22 articles were found. After anevaluation 2 studies were selected and the review was complemented with an analysis of randomized controlled trials in the previous seven bases using the key-words: Sleep apnea syndrome, Oral appliance and Randomized controlled trial. The search returned 37 articles, and after they were submitted to inclusion criteria 17 studies were selected. There are a small number of studies presenting the use of dental implants as a mean to assist the stabilization of the mandibular repositioning appliances; those that are available are case reports that focusing on the effectiveness of the technique. Studies examining the effect these appliances in dentate patients indicate improvement in the levels of apnea and snoring. The use of mandibular repositioning appliances in dentate patients is an effective technique in treatment of patients with obstructive sleep apnea syndrome mild/moderate. Randomized controlled trialsare required in order to enable an analysis of the use of mandibular repositioning devices with the aid of dental implants .

Risco da síndrome da apneia obstrutiva do sono em amostra populacional da cidade de Botucatu - SP

The most common sleep disorder is obstructive sleep apnea syndrome (OSAS), that is characterized by repeated pauses in breathing during sleep, resulting in partial or complete obstruction of the upper airway. It is associated with systemic arterial hypertension and obesity. Objective: To assess the frequency of OSAS in the adult population of Botucatu by the Berlin questionnaire. Method: Transveral study was performed in which the sample size was estimated at 385 individuals. The Berlin questionnaire was administered to adults randomly on the streets, supermarkets and local shops. Data were analyzed taking into account age, gender, "high risk for OSAS", hypertension, obesity and correlations for OSAS. Results: 468 people interviewed were aged between 18 and 95 years, average of 59 years. 166 (35.25%) individuals were identified as "high risk for OSAS", being more frequent in the population above 40 years. Obesity was present in 23.3%, more common in women (60.2%). 83.5% of the population obese also had a "high risk for OSAS". Hypertension was observed in 27.3%, of these 71.9% were at "high risk for OSAS". Conclusion: The study showed a high frequency of "high risk for OSAS" in the adult population. Despite the dissemination by the media about sleep apnea, patients are not investigated, even under medical care for hypertension.

Coupling between respiratory and sympathetic activities as a novel mechanism underpinning neurogenic hypertension

Enhanced sympathetic outflow to the heart and resistance vessels greatly contributes to the onset and maintenance of neurogenic hypertension. There is a consensus that the development of hypertension (clinical and experimental) is associated with an impairment of sympathetic reflex control by arterial baroreceptors. More recently, chronic peripheral chemoreflex activation, as observed in obstructive sleep apnea, has been proposed as another important risk factor for hypertension. In this review, we present and discuss recent experimental evidence showing that changes in the respiratory pattern, elicited by chronic intermittent hypoxia, play a key role in increasing sympathetic activity and arterial pressure in rats. This concept parallels results observed in other models of neurogenic hypertension, such as spontaneously hypertensive rats and rats with angiotensin II–salt-induced hypertension, pointing out alterations in the central coupling of respiratory and sympathetic activities as a novel mechanism underlying the development of neurogenic hypertension.

Relaxamento progressivo, stress, enfrentamento e qualidade de vida em pessoas com apneia obstrutiva do sono

Pós-graduação em Psicologia do Desenvolvimento e Aprendizagem - FC

Síndrome da apnéia obstrutiva do sono: diagnóstico e tratamento

The Syndrome Obstructive Sleep Apnea (OSA) is defined by recurrent episodes of a total or partial obstruction of the airway during sleep, considered apnea and hypopnea respectively. Considered to be increasing by increasing the number of individuals with a disorder breathing, Being continually increasing the number of individuals with a respiratory disorder, OSA can be considered a public health problem that deserves greater attention in relation to diagnoses and treatments that are being conducted. The objective of this study is through a literature review which should be evaluated during the diagnosis and etiology, consequences and treatment of respiratory disorders not adequately treated. The etiology is multifactorial and may be associated with exogenous factors or pathological and anatomical factors. In addition to the own symptoms interfere with the quality of life of the individual, depending on the intensity, OSA can trigger more serious complications. This is a complex syndrome which may have varying degrees and irreversible consequences to the body. The choice of treatment should be based on clinical conditions, the severity of the apnea, the degree of urgency of treatment and the patient's preferences, but the treatments available will not be fully effective if there are no changes in lifestyle of it. The respiratory disorders can range from a simple nasal obstruction and intermittent obstruction more severe, emphasizing the importance of a complete diagnosis, which must be multidisciplinary, through a team relationship between doctor and dentist.

Qualidade do sono em pacientes com síndrome do túnel do carpo

Pós-graduação em Bases Gerais da Cirurgia - FMB

Ensaio clínico randomizado duplo-cego do perfil inflamatório e do nível de estresse oxidativo em indivíduos com diagnóstico polissonográfico de SAOS antes e após o uso de CPAP

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Dinâmica de grafoelementos do sono e seus impactos na neurofisiologia de pacientes com apneia obstrutiva através de sinais de eletroencefalografia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Central leptin replacement enhances chemorespiratory responses in leptin-deficient mice independent of changes in body weight

Previous studies showed that leptin-deficient (ob/ob) mice develop obesity and impaired ventilatory responses to CO2 . In this study, we examined if leptin replacement improves chemorespiratory responses to hypercapnia (7 % CO2) in ob/ob mice and if these effects were due to changes in body weight or to the direct effects of leptin in the central nervous system (CNS). was measured via plethysmography in obese leptin-deficient- (ob/ob) and wild-type- (WT) mice before and after leptin (10 mu g/2 mu l day) or vehicle (phosphate buffer solution) were microinjected into the fourth ventricle for four consecutive days. Although baseline was similar between groups, obese ob/ob mice exhibited attenuated compared to WT mice (134 +/- 9 versus 196 +/- 10 ml min(-1)). Fourth ventricle leptin treatment in obese ob/ob mice significantly improved (from 131 +/- 15 to 197 +/- 10 ml min(-1)) by increasing tidal volume (from 0.38 +/- 0.03 to 0.55 +/- 0.02 ml, vehicle and leptin, respectively). Subcutaneous leptin administration at the same dose administered centrally did not change in ob/ob mice. Central leptin treatment in WT had no effect on . Since the fourth ventricle leptin treatment decreased body weight in ob/ob mice, we also examined in lean pair-weighted ob/ob mice and found it to be impaired compared to WT mice. Thus, leptin deficiency, rather than obesity, is the main cause of impaired in ob/ob mice and leptin appears to play an important role in regulating chemorespiratory response by its direct actions on the CNS.

Chronic Intermittent Hypoxia Depresses Afferent Neurotransmission in NTS Neurons by a Reduction in the Number of Active Synapses

Long-term synaptic plasticity has been recently described in brainstem areas associated to visceral afferent sensory integration. Chronic intermittent hypoxia (CIH), an animal model for studying obstructive sleep apnea in humans, depresses the afferent neurotransmission in nucleus tractus solitarii (NTS) neurons, which affect respiratory and autonomic regulation. Here we identified the synaptic mechanisms of CIH-induced depression of the afferent neurotransmission in NTS neurons in juvenile rats. We verified that CIH reduced the amplitude of both NMDA and non-NMDA glutamatergic excitatory currents (eEPSCs) evoked by tractus solitarii stimulation (TS-eEPSC) of second-order neurons in the NTS. No changes were observed in release probability, evidenced by absence of any CIH-elicited effects on short-term depression and failures in EPSCs evoked in low calcium. CIH also produced no changes in TS-eEPSC quantal size, since the amplitudes of both low calcium-evoked EPSCs and asynchronous TS-eEPSCs (evoked in the presence of Sr2+) were unchanged. Using single TS afferent fiber stimulation in slices from control and CIH rats we clearly show that CIH reduced the quantal content of the TS-eEPSCs without affecting the quantal size or release probability, suggesting a reduction in the number of active synapses as the mechanism of CIH induced TS-eEPSC depression. In accordance with this concept, the input-output relationship of stimulus intensity and TS-eEPSC amplitude shows an early saturation in CIH animals. These findings open new perspectives for a better understanding of the mechanisms underlying the synaptic plasticity in the brainstem sensory neurons under challenges such as those produced by CIH in experimental and pathological conditions.

The use of nasal dilator strips as a placebo for trials evaluating continuous positive airway pressure

OBJECTIVES: The aim of the current study was to compare the objective and subjective effects of continuous positive airway pressure to the use of nasal dilator strips in patients with acromegaly and moderate to severe obstructive sleep apnea. METHODS: We studied 12 patients with acromegaly and moderate to severe obstructive sleep apnea (male/females = 8/4, age = 52 +/- 8 ys, body mass index = 33.5 +/- 4.6 Kg/m(2), apnea-hypopnea index = 38 +/- 14 events/h) who had been included in a randomized, crossover study to receive three months of treatment with continuous positive airway pressure and nasal dilator strips. All patients were evaluated at study entry and at the end of each treatment by polysomnography, and Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index and treatment satisfaction questionnaires. ClinicalTrials.gov: NCT01265121 RESULTS: The apnea-hypopnea index values decreased significantly with continuous positive airway pressure treatment but did not change with the use of nasal dilator strips. All of the subjective symptoms improved with both treatments, but these improvements were significantly greater with continuous positive airway pressure than with the nasal dilator strips. CONCLUSION: The use of nasal dilator strips had a much smaller effect on the severity of obstructive sleep apnea in patients with acromegaly and moderate to severe obstructive sleep apnea in comparison to the use of continuous positive airway pressure. Moreover, the improvement in several subjective parameters without any significant objective improvement in obstructive sleep apnea resulting from the use of nasal dilator strips is compatible with a placebo effect.