Introdução. Sabe-se que a terapia de ressincronização cardíaca (TRC) aumenta a capacidade ao esforço e reduz a ativação simpática em pacientes com insuficiência cardíaca (IC). Por outro lado, existem evidências de que o treinamento físico (TF) melhora o controle neurovascular, tolerância ao exercício e qualidade de vida dos pacientes com IC. Neste estudo, nós testamos a hipótese de que o TF associado à TRC diminuiria a atividade nervosa simpática muscular (ANSM) e a vasoconstrição periférica. Adicionalmente, esta associação de TRC e TF melhoraria a função cardíaca, consumo de oxigênio pico e qualidade de vida nesses pacientes. Métodos. Vinte e oito pacientes com IC submetidos há um mês de TRC e fração de ejeção < 35% foram consecutivamente e aleatoriamente divididos em dois grupos: treinados (TRCt, n=14, 54 ± 4 anos) e não-treinados (TRCs, n=14, 57 ± 1 anos). Um grupo de indivíduos controles saudáveis também foi incluído no estudo (n=11, 43 ± 4 anos). A ANSM foi avaliada diretamente pela técnica de microneurografia. O fluxo sanguíneo muscular foi avaliado pela técnica de pletismografia de oclusão venosa. A capacidade física foi avaliada pelo teste cardiopulmonar, a função cardíaca pelo ecocardiograma e a qualidade de vida pelo questionário Minnesota Living with Heart Failure. O TF foi realizado em esteira ergométrica por 40 minutos, 3 vezes por semana, durante 4 meses. Resultados. No período pré-intervenção, a ANSM foi significativamente maior (p=0,01) nos pacientes com IC quando comparados com os indivíduos saudáveis. O fluxo sanguíneo muscular não foi diferente entre os grupos estudados (p=0,24). Após quatro meses de treinamento físico, a ANSM foi reduzida (65 ± 7 vs 43 ± 8 disparos/100batimentos, p < 0,001), atingindo níveis semelhantes àqueles observados nos indivíduos saudáveis (43 ± 8 vs 31 ± 3 disparos/100batimentos, p=0,44). Além disso, o TF associado a TRC aumentou o FSM (1,63 ± 0,14 vs 1,85 ± 0,12 ml/min/100ml, p=0,02), a fração de ejeção (28 ± 3 vs 33 ± 4%, p=0,04) e a capacidade funcional (18,5 ± 1,1 vs 21,5 ± 1,7 ml/kg/min, p=0,04), o que não foi observado no grupo TRCs. Não houve alteração significativa na qualidade de vida dos pacientes (26 ± 4 vs 20 ± 4, p=0,11). Conclusão. O treinamento físico associado à TRC melhora expressivamente o controle neurovascular, a função cardíaca e a capacidade física em pacientes com IC. Estes achados destacam a importância da inclusão do treinamento físico no tratamento de pacientes com IC submetidos à TRC / Background. Cardiac Resynchronization Therapy (CRT) is known to increase exercise capacity and decrease sympathetic activation in HF. On the other hand, there is evidence that exercise training improves neurovascular control, physical capacity and quality of life in HF patients. We tested the hypothesis that exercise training (ET) associated with CRT would reduce muscle sympathetic nerve activity (MSNA) and peripheral vasoconstriction in chronic heart failure patients. In addition, the association of CRT and ET would improve cardiac function, peak oxygen consumption and quality of life in these patients. Methods. Twenty-eight HF patients submitted a month of CRT, EF < 35%, with CRT for 1 month were consecutively and randomly divided into two groups: Exercise-trained (CRTt, n=14, 54 ± 4 years old) and untrained (CRTs, n=14, 57 ± 1 years old). A control group was also involved in the study (n=11, 43 ± 4 years). MSNA was directly evaluated by microneurography technique and forearm blood flow by venous occlusion plethysmography. Peak VO2 was determined by cardiopulmonary exercise test, cardiac function by echocardiography and quality of life by Minnesota Living with Heart Failure questionnaire. ET consisted of three 40-minute exercise sessions per week on a treadmill for four months. Results. Baseline MSNA was significantly higher (p=0.01) in heart failure patients when compared with healthy controls. The forearm blood flow was not different between groups (p=0.24). After four months of ET, MSNA was significantly reduced (65±7 vs 43±8 bursts/100 heart beats, p < 0.001) reaching levels similar to those observed in healthy subjects (43±8 vs. 31±3 bursts/100 heart beats, p=0.44). Furthermore, ET associated with CRT increased forearm blood flow (1.63±0.14 vs. 1.85±0.12 ml/min/100ml, p=0.02), EF (28±3 vs. 33±4%, p=0.04) and peak VO2 (18.5±1.1 vs 21.5 ± 1.7 ml/kg/min, p=0.04), which was not observed in the CRTs. There was not significant changes in the quality of life of patients (26 ± 4 vs. 20 ± 4, p=0.11). Conclusions. ET associated with CRT improves neurovascular control, cardiac function and functional capacity in heart failure patients. These findings highlight the importance of including ET in the treatment of heart failure patients submitted to CRT

Introdução: O papel do sistema nervoso simpático (SNS) na remodelação ventricular esquerda na insuficiência aórtica crônica (IAo) é pouco conhecido. O aumento da atividade do SNS tem associação com remodelamento ventricular e mau prognóstico na insuficiência cardíaca (IC) não valvar, fazendo do seu bloqueio farmacológico importante conduta terapêutica. A despeito de similaridades na evolução clínica da IAo com IC não valvar, não há estudos com mensuração direta da atividade do SNS em IAo. Objetivo: Quantificar a atividade nervosa simpática muscular (ANSM) em pacientes com IAo importante em três situações clínicas, representativas da história natural dessa doença. Métodos: Trata-se de estudo transversal, unicêntrico, incluindo 30 pacientes com IAo importante que foram alocados em três grupos: (I) assintomáticos (n = 10, 70% homens, 37,4 ± 13,6 anos), (II) sintomáticos em pré-operatório de troca de valva aórtica (TVA) (n = 10, 70% homens, 42,2 ± 12,1 anos) e (III) - pós-operatório de TVA (n = 10, 80% homens, 41,2 ± 15,4 anos). Grupo controle formado por voluntários saudáveis sem doença cardíaca estrutural (n = 10) correspondentes para idade, sexo e IMC também foram avaliados. Variáveis clínicas, ecocardiográficas e BNP (peptídeo natriurético atrial) foram analisadas nos grupos. Apenas a pressão arterial sistólica era significativamente menor no grupo III. A ANSM foi mensurada utilizando a técnica padrão de microneurografia muscular (MM). A variável desfecho foi a Resumo média do número de espículas obtidas num registro contínuo de 10 minutos de MM. Resultados: Os grupos IAo não diferiram em relação às características demográficas, antropométricas e ecocardiográficas, assim como etiologia e BNP. A média de espículas obtidas pela MM, representativa da ANSM, nos grupos I, II, III e controle foi, respectivamente, 25,5 ± 4,1, 25,1 ± 3,6, 28,6 ± 6,5 e 15,6 ± 1,5 (p=0,001). Houve apenas diferença estatística entre os grupos IAo e o grupo controle. Conclusão: Houve aumento significativo da ANSM em pacientes com IAo importante associado ao remodelamento ventricular esquerdo em relação a indivíduos sem doença cardíaca estrutural. A ANSM foi similar em pacientes com IAo importante assintomáticos, sintomáticos e em pós-operatório de TVA. A participação da ação do SNS na IAo deve estar associada ao remodelamento ventricular, mas sem correlação com mudanças clínicas / Introduction: The role of sympathetic nervous system (SNS) in the left ventricle remodeling of severe aortic regurgitation (AR) remains poorly understood. The increase in SNS activity is associated with ventricular remodeling and poor prognosis in non-valvular heart failure (HF), making its pharmacological blockade an important therapeutic approach. Despite similarities in the clinical evolution of AR with non-valvular HF, there are no studies with direct measurement of SNS activity in AR. Aims: The present study aimed to quantify muscular sympathetic nervous activity (MSNA) in patients with severe AR in three clinical situations: asymptomatic, symptomatic before aortic valve replacement (AVR), and patients submitted to AVR. Methods: Thirty patients with severe AR were allocated to three groups: (I) asymptomatic patients (n=10, 70% men, age: 37.4 ± 13.6), (II) symptomatic patients before AVR (n=10, 70% men, age: 42.2 ± 12.1), and (III) patients submitted to AVR (n=10, 80% men, age: 41.2 ± 15.4). Healthy volunteers (n = 10) matched for age, sex, and BMI were also assessed. The AR groups did not differ in relation to etiology, demographic, anthropometric or echocardiographic data. Only systolic blood pressure was significantly lower in group III. MSNA was recorded using microneurography, with a spike per minute result. Results: The means of 10-minute recordings in groups I, II, III and control were 23.2 ± 6.4, 25.5 ± 4.1, 25.1 ± 3.6 and 15.6 ± 1.5, respectively (p=0.001). Only the AR and control groups differed from each other. Conclusions: AR is associated with relatively higher SNS activity, which is similar across different stages of the disease (asymptomatic, symptomatic and postoperative). The role of the SNS in AR must be associated with ventricular remodeling, but without correlation with clinical change

Introdução. Apneia obstrutiva do sono (AOS) provoca alterações autonômicas, tais como, hipersensibilidade quimiorreflexa e diminuição da sensibilidade barorreflexa e metaborreflexa muscular que contribuem para a hiperativação simpática em indivíduos que sofrem desse distúrbio. O objetivo desse estudo foi avaliar o efeito do treinamento físico no controle metaborreflexo da atividade nervosa simpática muscular (ANSM) em indivíduos com apneia obstrutiva do sono. Métodos. Todos os indivíduos triados para este estudo foram submetidos à polissonografia noturna convencional e avaliação da capacidade cardiorrespiratória em esforço. Quarenta e um adultos sedentários com AOS moderada e severa foram aleatoriamente divididos em grupo não-treinado (AOSNT, n=21) e treinado (AOST, n=20). A ANSM foi avaliada pela técnica microneurografia, o fluxo sanguíneo muscular (FSM) por pletismografia de oclusão venosa, a frequência cardíaca (FC) pelo eletrocardiograma e a pressão arterial (PA) método oscilométrico automático. Todas as variáveis fisiológicas foram avaliadas simultaneamente durante quatro minutos de repouso, seguido de três minutos de exercício isométrico de preensão manual a 30% da contração voluntária máxima, seguido por dois minutos de oclusão circulatória pós-exercício (OCPE) do segmento corporal previamente exercitado. A ativação seletiva do controle metaborrelfexo foi calculada pela diferença da ANSM do primeiro e segundo minutos da OCPE e a média da ANSM no repouso. Resultados. Os grupos foram semelhantes em gênero, idade, parâmetros antropométricos, parâmetros neurovasculares, parâmetros hemodinâmicos e parâmetros do sono. O treinamento físico reduziu a ANSM e aumentou o FSM no repouso. O treinamento físico diminuiu significativamente os níveis de ANSM e aumentou a resposta de FSM durante o exercício isométrico de preensão manual. O treinamento físico não alterou as respostas de frequência cardíaca e de PA durante o exercício isométrico. Em relação à sensibilidade metaborreflexa, o treinamento físico aumentou significativamente as respostas da ANSM no 1º minuto de OCPE. Não foram observadas diferenças significativas no FSM, FC e PA após o treinamento físico. Conclusões. O treinamento físico aumenta a sensibilidade metaborreflexa muscular em indivíduos com AOS, o que pode contribuir, pelo menos em parte, para a melhora no controle neurovascular durante o exercício nesses pacientes / Introduction. Obstructive sleep apnea (OSA) causes autonomic dysfunction, such as, chemoreflex hypersensitivity and baroreflex impairment and muscle metaboreflex decrease, which contribute to sympathetic overactivity in subjects who suffer from this disturbance. The purpose of this study was evaluated the effect of exercise training on muscle metaboreflex control of muscle sympathetic nerve activity (MSNA) in subjects with OSA. Methods. All individuals selected for this study underwent overnight polysomnography and cardiopulmonary exercise testing. Forty-one untrained adults with moderate to severe OSA were randomly divided into non-trained (AOSNT, n=21) and trained (AOST, n=20) groups. MSNA was assessed by microneurography technique, muscle blood flow (FBF) by venous occlusion plethysmography, heart rate (HR) by electrocardiography and blood pressure (BP) by noninvasively automated oscillometric device. All physiological variables were simultaneously assessed for 4 minutes at rest, followed by three minutes of isometric handgrip exercise at 30% of maximal voluntary contraction, followed by two minutes of postexercise regional circulatory arrest (PECA). Muscle metaboreflex sensitivity was calculated as the difference in MSNA at first and second minute of PECA and MSNA at rest period. Results. AOSNT and AOST groups were similarly in gender, age, anthropometric, neurovascular, hemodynamic and sleep parameters. Exercise training reduced MSNA and increased FBF. Exercise training significantly reduced MSNA levels and increased FBF responses during isometric handgrip exercise. Regarding the metaboreflex sensitivity, exercise training significantly increased MSNA response at 1st minute of PECA. There were no significantly difference in FBF, HR and BP after exercise training. Conclusions. Exercise training increases muscle metaboreflex sensitivity in patients with OSA, which seems to contribute, at least in part, to the improvement in neurovascular control during exercise in these patients

Calcium sensitization represents a mechanism that enables vascular smooth muscle cells to change the sensitivity of the contractile apparatus to intracellular calcium The aim of this study was to determine to what extent is calcium sensitization modulated by the renin- angiotensin system (RAS), sympathetic nervous system (SNS), nitric oxide (NO) and prostanoids produced by cyclooxygenase (COX). For this purpose we studied the effects of acute and chronic blockade of particular systems on blood pressure changes elicited in conscious normotensive rats by administration of Rho-kinase inhibitor fasudil. Adult male chronically cannulated Wistar rats were used in all experiments. Main findings of this study are as follow: 1) Decrease of blood pressure elicited by Rho-kinase inhibition was enhanced under the conditions of acute NOS inhibition. Inhibition of NOS was shown to have a bigger effect than COX inhibition (this was confirmed under the conditions of acute RAS and SNS inhibition as well). These findings are in agreement with the hypothesis that NO exerts a suppressive effect on calcium sensitization. 2) Chronic NOS inhibition caused hypertension characterized by a more pronounced blood pressure lowering after Rho-kinase inhibition in comparison with control. NO chronically suppresses the calcium...

The purpose of this study was to examine Dienstbier's (1989) hypothesis that SAM elicitation is prompted by subject's cognitive expectations of an acute stressor ('challenge' or 'threat' appraisal). Reported anxiety was also measured.

Subjects participating in magnetic resonance imaging (MRI) examinations regularly report anxiety and stress related reactions. This may result in impaired data quality and premature termination of scans. Moreover, cognitive functions and neural substrates can be altered by stress. While prior studies investigated pre–post scan differences in stress reactions only, the present study provides an in-depth analysis of mood changes and hormonal fluctuations during the time course of a typical fMRI session. Thirty-nine subjects participated in the study. Subjective mood, salivary alpha-amylase (sAA) and cortisol were assessed at six time points during the lab visit. Associations between hormonal data and neural correlates of a visual detection task were observed using a region of interest approach applied to the thalamic region. Mood and hormonal levels changed significantly during the experiment. Subjects were most nervous immediately after entering the scanner. SAA was significantly elevated after MRI preparation. A subgroup of n = 5 (12.8%) subjects showed pronounced cortisol responses exceeding 2.5 nmol/l. Preliminary fMRI data revealed an association between sAA levels and left thalamic activity during the first half of the experiment that disappeared during the second half. No significant correlation between cortisol and thalamic activity was observed. Results indicate that an fMRI experiment may elicit subjective and neuroendocrine stress reactions that can influence functional activation patterns.

Understanding physiological responses to threat can inform therapeutic interventions for phobias, anxieties, and PTSD. The defense cascade is reviewed as a theoretical model that predicts behavioral and physiological responses to threats. Nineteen undergraduates (five male), average age 19.4 experienced a novel virtual reality (VR) threat scenario while their physiology was measured. The Subjective Units of Distress Scale (SUDS) was used as a self-report indicator of distress in the research setting. Averaged SUDS reports suggested that the VR stimulus was experienced as threatening for most participants, but their autonomic response patterns did not fit those predicted by the defense cascade. Participants who had scored high on adaptive response questionnaires tended to show uncoupled ANS activation during baseline, but varied across the stimulus condition. Nearly all participants showed either coactivation or reciprocal activation during the stimulus period except those reporting the most dissociative trauma experiences, who mostly showed uncoupled ANS activation. / M.S. / The more we understand about how people’s bodies and their energies act when they feel threatened, the better we can find help for folks who struggle with anxiety, trauma or other challenging conditions. This research uses a theoretical model called the defense cascade to explore how people respond mentally and physically to threatening situations. Nineteen undergraduates went through a virtual reality (VR) experience that was designed to feel threatening while their body and its energy systems were measured. A scale was introduced called the Subjective Units of Distress Scale (SUDS) and was used to help the researchers understand how distressed people felt while they were in the VR experience. Averaged SUDS reports suggested that the VR stimulus was experienced as threatening for most participants, but their body response patterns did not fit those predicted by the defense cascade. Participants whose questionnaire responses suggested they were not anxiety-prone or traumatized, tended to show bodily activation that uncoupled their two autonomic bodily systems during a baseline period before the threatening stimulus. However, their autonomic responses during the stimulus period varied. Nearly all participants showed either both autonomic systems acting together or only one system acting in a mutually exclusive way to the other system during the stimulus period. This was the case for most participants except those reporting the most trauma involving dissociative experiences. This latter group mostly showed uncoupled autonomic bodily patterns.

Indiana University-Purdue University Indianapolis (IUPUI) / The sympathetic nervous system strongly modulates the contractile and electrical function of the heart. The anatomical underpinnings that enable a spatially and temporally coordinated dissemination of sympathetic signals within the cardiac tissue are only incompletely characterized. In this work we took the first step of unraveling the in situ 3D microarchitecture of the cardiac sympathetic nervous system. Using a combination of two-photon excitation fluorescence microscopy and computer-assisted image analyses, we reconstructed the sympathetic network in a portion of the left ventricular epicardium from adult transgenic mice expressing a fluorescent reporter protein in all peripheral sympathetic neurons. The reconstruction revealed several organizational principles of the local sympathetic tree that synergize to enable a coordinated and efficient signal transfer to the target tissue. First, synaptic boutons are aligned with high density along much of axon-cell contacts. Second, axon segments are oriented parallel to the main, i.e., longitudinal, axes of their apposed cardiomyocytes, optimizing the frequency of transmitter release sites per axon/per cardiomyocyte. Third, the local network was partitioned into branched and/or looped sub-trees which extended both radially and tangentially through the image volume. Fourth, sub-trees arrange to not much overlap, giving rise to multiple annexed innervation domains of variable complexity and configuration. The sympathetic network in the epicardial border zone of a chronic myocardial infarction was observed to undergo substantive remodeling, which included almost complete loss of fibers at depths >10 µm from the surface, spatially heterogeneous gain of axons, irregularly shaped synaptic boutons, and formation of axonal plexuses composed of nested loops of variable length. In conclusion, we provide, to the best of our knowledge, the first in situ 3D reconstruction of the local cardiac sympathetic network in normal and injured mammalian myocardium. Mapping the sympathetic network connectivity will aid in elucidating its role in sympathetic signal transmisson and processing.

<p>Uvod: Primarna fokalna hiperhidroza (PFH) je poremećaj nepoznate etiologije koji se karakteri&scaron;e prekomernim znojenjem na predilekcionim mestima. Podjednako se javlja kod osoba mu&scaron;kog i ženskog pola tokom dvadesetih i početkom tridesetih godina života, pri čemu se smatra da je učestalos PFH oko 2,8% u ukupnoj populaciji. Nastaje kao posledica hiperaktivnosti simaptičkog nervnog sistema ka znojnim žlezdama. Karakteristično je za PFH da se ne javlja noću, &scaron;to sugeri&scaron;e da emocionalni stimulus igra bitnu ulogu u nastanku ovog poremećaja. Bilateralna torakoskopska simpatektomija (BTS) je minimalno invazivna hirur&scaron;ka procedura koja se danas primenjuje u trajnom lečenju PFH, sa niskom stopom komplikacija i omogućava lečenje kao jednodnevne hirur&scaron;ke procedure. Ciljevi ovog istraživanja su bili: a) da se ispita ukupna efikasnost BTS na trajno smanjenje PFH predilekcionih delova tela - dlanova, pazu&scaron;nih jama, lica i stopala; b) da se ispita efiksanost BTS kod osoba sa PFH u odnosu na različite nivoe transekcije simpatičkog lanca; c) da se ispita uticaj BTS na plućnu i srčanu funkciju kod operisanih osoba sa PFH; d) da se ispita pojava, trajanje i intenzitet kompenzatornog znojenja nakon BTS kod operisanih osoba sa PFH; e) da se ispita pojava, trajanje, lokalizacija i tretman postoperativnog bola nakon BTS kod osoba sa PFH; f) da se utvrde postoperativne komplikacije BTS kod osoba sa PFH; i g) da se ispita uticaj BTS na kvalitet života kod operisanih osoba sa PFH. Radna hipoteza istraživanja je bila da hirur&scaron;ka procedura - minimlano invazivna BTS ima značajan efekat na prekomerno znojenje na predilekcionim mestima kod osoba sa PFH, da je praćena sa minimalnim morbiditetom, bez kliničkog uticaja na plućnu i srčanu funkciju i da značajno pobolj&scaron;ava kvalitet života operisanih osoba. Materijal i metod: Urađena je prospektivna klinička studija koja je uključila 435 osoba sa PFH, koji su operisani bilateralnom torakoskopskom simpatektomijom, na Klinici za grudnu hirurgiju, Instituta za plućne bolesti Vojvodine u Sremskoj Kamenici između 2010 i 2014 godine. Kriterijumi za uključivanje u studiju bili su: a) da su osobe sa utvrđenom i procenjenom PFH pristale da učestvuju u istraživanju ispunjavajući preoperativno i postoperativno upitnike o efektima BTS i kvalitetu života nakon operacije; b) da nisu imali prethodne grudno hirur&scaron;ke intervencije, frakture rebara, masivne pneumonije ili empijem pleure; c) da nisu imali te&scaron;ki poremećaj plućne ili srčane funkcije; d) da ne boluju od sekundarne hiperhidroze. Primarna fokalna hiperhidroza je bila ustanovljena i procenjena anamnestičkim podacima, kliničkom slikom i pregledom koji je bio fokusiran na kvalitativno ispitivanje. Bilateralna torakoskopska simpatektomija izvođena je u op&scaron;toj anesteziji, a transekcija simpatičkog lanca je rađena pomoću ultrazvučno aktiviranog skalpela. Osobe sa izvedenom BTS zbog PFH bile su klasifikovane u tri grupe, u zavisnosti od nivoa transekcije simpatičkog lanca: a) transekcija na nivou drugog do četvrtog torakalnog gangliona (T2-T4); b) transekcija na nivou trećeg do četvrtog torakalnog gangliona (T3-T4); i c) transekcija na nivou drugog do trećeg torakalnog gangliona (T2-T3). Za procenu kompenzatornog znojenja i kvaliteta života kori&scaron;ćene je: Hyperhidrosis Disease Severity Scale (HDSS) za intenzitet kompenzatornog znojenja i kvaliteta života nakon BTS. Rezultati: Od 435 osoba sa PFH kod kojih je urađena BTS, bilo je 142 (32,64%) osobe mu&scaron;kog pola i 293 (67,36%) osoba ženskog pola, prosečne starosti od 29,68&plusmn;7,6 godina. Pozitivan nasledni faktor navelo je 167 osoba (38,62%). Najče&scaron;ća lokalizacija prekomernog znojenja kod osoba u ovom istraživanju je bila kombinacija dlanova, pazu&scaron;nih jama i tabana, koju je imalo 167 osoba (38,39%). Pre operacije, preko 60% ispitivanih osoba je navelo da im je kvalitet života lo&scaron; ili izuzetno lo&scaron;. Kod svih operisanih osoba u ovom istraživanju, operacija je izvedena uspe&scaron;no obostrano. Nije bilo smrtnih ishoda. Od intraoperativnih komplikacija zabeležena je jedna konverzija (0,23%) u minitorakotomiju zbog krvavljenja iz interkostalne vene. Neposredni postoperativni uspeh BTS kod operisanih osoba zbog PFH, a na osnovu prve kontrole posle nedelju dana bio je zabeležen kod svih (99,54%), osim kod dve osobe (0,46%) koje su imale postoperativne komplikacije: pareza n. ulnarisa i Hornerov sindrom kod jedne osobe i Horner sindrom kod druge osobe. Postoperativni morbiditet nakon BTS bio je zabeležen kod 32 osobe (7,35%). Izrazito pobolj&scaron;anje, odnosno značajno smanjenje znojenja kod osoba sa PFH zabeleženo je kod 428 operisanih (98,39%). Osobe sa transekcijom simpatičkog lanca na nivou gangliona T3-T4 imali su najbolji rezultat sa pobolj&scaron;anjem kvaliteta života u 85,03% operisanih. Kompenzatorno znojenje se nakon BTS javilo kod 316 (72,64%) operisanih osoba, a samo 2,53% je navelo da je postoperativno kompenzatorno znojenje izuzetno jakog intenziteta. Postoperativni bol bio je prisutan kod 79,77% operisanih osoba, sa prosečnim trajanjem do dve nedelje. Analgetike je postoperativno koristilo 24,21% anketiranih osoba. Od 287 operisanih osoba u ovom istraživanju, koji su pre operacije naveli da su imali i prekomerno znojenje tabana, nakon 6 meseci 185 osoba (64,46%) je navelo da se prekomerno znojenje tabana smanjilo. Iako postoji statistička značajnost u promeni vitalnog kapaciteta u smislu njegovog povećanja &scaron;est meseci nakon BTS (sa 4,49&plusmn;1,15 L na 4,54&plusmn;1,11 L), ta promena nije bila klinički relevantna. Promene u krvnom pritisku i srčanom pulsu, iako zabeležene, takođe nisu imale klinički značaj. Kvalitet života, pre BTS ocenjen kao lo&scaron; (i izuzetno lo&scaron;) bio je prisutan kod 265 osoba (60, 92%), a 6 meseci posle operacije ocenjen je kao odličan i dobar kod 428 osoba (98,39%). Zaključak: BTS kao minimalno invazivna hirur&scaron;ka procedura kod osoba sa PFH ima minimalni morbiditet, a visoku uspe&scaron;nost u smanjenju prekomernog znojenja na predilekcionim mestima, sa pobolj&scaron;anjem kvaliteta života kod 98,39% operisanih, sa minimalnim promenama plućne i srčane funkcije koje nisu klinički relevantne.</p> / <p>Primary focal hyperhidrosis (PFH) is a disorder of an unknown etiology, characterized by excessive sweating of predilective parts of the body. It affects men and women equally, with a peak incidence in the later second and early third decades of life, with incidence of up to 2,8% of the world population. It is caused by hyperactivity of the sympathetic nervous system to the sweat glands. It has been shown that PFH does not occur during the sleeping times, which suggests that emotional stimuli play an important role in this disorder. Bilateral thoracoscopic sympathectomy (BTS) is minimal invasive surgical procedure, which has evolved into an effective and permanent treatment for severe PFH, with low rate of morbidity and it can be performed as the one day surgical procedure. The aims of this investigation were: a) to examine the overall efficiency of BTS on permanent reduction of PFH of predilective parts of the body-palms, armpits, faces and soles; b) to examine the efficiency of BTS with different levels of transection among the persons with the PFH; c) to examine the influence of BTS on cardio-pulmonary function tests in persons with PFH after the operation; d) to examine the incidence, duration and intensity of compensatory sweating after BTS among persons with PFH; e) to examine the incidence, duration, localization and treatment of postoperative pain after BTS among persons with PFH; f) to determine postoperative complications of BTS among persons with PFH; g) to examine the influence of BTS on quality of life among persons with PFH. The working hypothesis of this investigation is that surgical procedure &ndash; minimal invasive BTS has the permanent effect on excessive sweating of predilective parts of the body among persons with PFH, followed by minimal morbidity, without clinical influence on cardio-pulmonary function and significantly improves the quality of life among persons with PFH. This was a prospective clinical study which included 435 patients with PFH, who have been operated with BTS, at the Clinic for Thoracic surgery, the Institute for pulmonary diseases of Vojvodina, Sremska Kamenica, between 2010 and 2014. The including criteria for the investigation were: a) persons with confirmed and estimated PFH accepted to participate in this investigation, fulfilling pre and postoperatively questionnaire about BTS effects and quality of life after the operation; b) absence of previous thoracic surgical procedures, rib fractures, massive pneumonias or pleural empyema; c) satisfactory cardio-respiratory function; d) absence of secondary hyperhidrosis. Primary focal hyperhidrosis was confirmed and estimated by anamnesis, clinical examination focused on qualitatively examination. Bilateral thoracoscopic sympathectomy was performed with general anesthesia, using harmonic scalpel for transection of sympathetic chain. Persons with PFH who underwent the BTS were classified into three groups, depending the level of transaction of sympathetic chain: a) transection at the level from the second to the forth thoracic sympathetic ganglion (T2-T4); b) transection at the level from the third to the forth thoracic sympathetic ganglion (T3-T4); c) transection at the level from the second to the third thoracic sympathetic ganglion (T2-T3). For the assessment of postoperative pain, compensatory sweating and quality of life next scales have been used: standardized numeric pain rating scale and Hyperhidrosis Disease Severity Scale (HDSS) for intensity of compensatory sweating and quality of life. Among 435 persons with PFH who underwent the BTS in this investigation, 142 (32,64%) were male and 293 (67,36%) female persons, with mean age of 29,68&plusmn;7,6. There was no mortality or serious intraoperative complications that required operative conversio from minimal invasive surgical procedure to thoracotomy. Among 435 persons with PFH who underwent the BTS in this investigation, 142 (32,64%) were male and 293 (67,36%) female persons, with mean age of 29,68&plusmn;7,6. Positive genetic factor has been found in 167 persons (38,62%). The most common localisation of excessive sweating in this investigation was the combination of palms, armpits and soles in 167 persons (38,39%). Before the operation, over 60% of persons estimated their quallity of life as bad or very bad. The operation was successfully performed in all patients bilaterally. There was no mortality in this investigation. There was one intraoperative complication, bleeding from intercostal vein, requiring conversion to minithoracotomy. Immediatelly postoperative success after BTS seven days after the operation was achieved in all persons accepted in two persons (0,46%) due to the postoperative complications: nervous ulnaris paresis and Horner syndrome in one person and Horener syndome in the other person. Postoperative morbidity after the BTS was recoreded in 32 persons (7,35%). Marked improvement, as significant reduction of sweating in persons with PFH was achieved in 428 operated persons (98,39%). Transection of sympathetic chain on level T3-T4 achieved improvement of quality of life in 85,03% operated persons with PFH. Compensatory sweating after the BTS has occurred in 316 (72,64%) operated persons, but only 2,53% operated persons declared compensatory sweating as severe. Postoperative pain was presented in 79,77% operated persons, with average duration of two weeks. Analgetics used only 24,21% of operated persons. There were 287 operated persons in this investigation, who claimed to have plantar hyperhidrosis before the operation and six months after the operation 185 persons (64,46%) claimed to have a reduction of plantar sweating. Although there was a clinical significance in changes of vital capacity after the BTS (from 4,49&plusmn;1,15 L to 4,54&plusmn;1,11 L), ther was no clinical significance. Changes in blood pressure and heart rate, although recoreded, had no clinical significance. Quality of life, before the BTS was recorded as bad or very bad in 265 persons (60,92%), and six months after the operation as excellent or good in 428 persons (98,39%) persons. Conclusion: In patients with PFH, BTS as minimal invasive surgical procedure, has a minimal morbidity and high success in treatment of excessive sweating, with improvemnet of quality of life in 98,39% operated person, with changes in cardio-pulmonary functions that are not clinical relevant.</p>

L’hypertrophie du ventricule gauche (HVG) est un processus adaptif et compensatoire qui se développe conséquemment à l’hypertension artérielle pour s’opposer à l’élévation chronique de la pression artérielle. L’HVG est caractérisée par une hypertrophie des cardiomyocytes suite à l’augmentation de la synthèse d’ADN, une prolifération des fibroblastes, une augmentation du dépôt de collagène et une altération de la matrice extracellulaire (MEC). Ces changements génèrent des troubles de relaxation et mènent au dysfonctionnement diastolique, ce qui diminue la performance cardiaque. La suractivité du système nerveux sympathique (SNS) joue un rôle essentiel dans le développement de l’hypertension artérielle et de l’HVG à cause de la libération excessive des catécholamines et de leurs effets sur la sécrétion des cytokines pro-inflammatoires et sur les différentes voies de signalisation hypertrophiques et prolifératives. Le traitement antihypertenseur avec de la moxonidine, un composé sympatholytique d’action centrale, permet une régression de l’HVG suite à une réduction soutenue de la synthèse d'ADN et d’une stimulation transitoire de la fragmentation de l'ADN qui se produit au début du traitement. En raison de l’interaction entre l’HVG, les cytokines inflammatoires, le SNS et leurs effets sur les protéines de signalisation hypertrophiques, l’objectif de cette étude est de détecter dans un modèle animal d’hypertension artérielle et d’HVG, les différentes voies de signalisation associées à la régression de l’HVG et à la performance cardiaque. Des rats spontanément hypertendus (SHR, 12 semaines) ont reçu de la moxonidine à 0, 100 et 400 µg/kg/h, pour une période de 1 et 4 semaines, via des mini-pompes osmotiques implantées d’une façon sous-cutanée. Après 4 semaines de traitement, la performance cardiaque a été mesurée par écho-doppler. Les rats ont ensuite été euthanasiés, le sang a été recueilli pour mesurer les concentrations des cytokines plasmatiques et les cœurs ont été prélevés pour la détermination histologique du dépôt de collagène et de l'expression des protéines de signalisation dans le ventricule gauche. Le traitement de 4 semaines n’a eu aucun effet sur les paramètres systoliques mais a permis d’améliorer les paramètres diastoliques ainsi que la performance cardiaque globale. Par rapport au véhicule, la moxonidine (400 µg/kg/h) a permis d’augmenter transitoirement la concentration plasmatique de l’IL-1β après une semaine et de réduire la masse ventriculaire gauche. De même, on a observé une diminution du dépôt de collagène et des concentrations plasmatiques des cytokines IL-6 et TNF-α, ainsi qu’une diminution de la phosphorylation de p38 et d’Akt dans le ventricule gauche après 1 et 4 semaines de traitement, et cela avec une réduction de la pression artérielle et de la fréquence cardiaque. Fait intéressant, les effets anti-hypertrophiques, anti-fibrotiques et anti-inflammatoires de la moxonidine ont pu être observés avec la dose sous-hypotensive (100 µg/kg/h). Ces résultats suggèrent des effets cardiovasculaires bénéfiques de la moxonidine associés à une amélioration de la performance cardiaque, une régulation de l'inflammation en diminuant les niveaux plasmatiques des cytokines pro-inflammatoires ainsi qu’en inhibant la MAPK p38 et Akt, et nous permettent de suggérer que, outre l'inhibition du SNS, moxonidine peut agir sur des sites périphériques. / Left ventricular hypertrophy (LVH) is an adaptive and compensatory process that develops in hypertension to oppose the chronic elevation of blood pressure. LVH is characterized by hypertrophy of cardiomyocytes following the increase in DNA synthesis, proliferation of fibroblasts, increased collagen deposition and alteration of the extracellular matrix (ECM). These changes generate relaxation and diastolic dysfunction which reduced cardiac performance. The overactivity of the sympathetic nervous system plays an essential role in the development of hypertension and left ventricular hypertrophy pathogenesis due to the excessive release of catecholamines and norepinephrine spillover and their effects on the secretion of pro-inflammatory cytokines and hypertrophic signaling pathways. Antihypertensive treatment with moxonidine, a centrally acting sympatholytic imidazoline compound, results in prevention of left ventricular hypertrophy, resulting from a sustained reduction of DNA synthesis and transient stimulation of DNA fragmentation that occur early after treatment. Due to the interaction between LVH, inflammatory cytokines, the SNS and their effects on hypertrophic signaling proteins, the objective of this study is to detect in an animal model of hypertension and LVH, the different signaling pathways associated with regression of LVH and cardiac performance. Spontaneously hypertensive rats (SHR, 12 weeks old) received moxonidine at 0, 100 and 400 µg/kg/h, for 1 and 4 weeks, via subcutaneously implanted osmotic minipumps. After 4 weeks of treatment, cardiac performance was measured by echo-Doppler. Then the rats were euthanized, blood was collected for measurement of plasma cytokines and hearts for histologic determination of collagen deposition and for measurement of left ventricular expression of downstream signaling proteins. Treatment for 4 weeks had no effect on systolic parameters but improved diastolic parameters and global cardiac performance. Compared to vehicle, moxonidine (400 µg/kg/h) transiently increased plasma IL-1β after 1 week and reduced left ventricular mass. Similarly, there was a decrease in collagen deposition and plasma concentrations of IL-6 and TNF-α, and decreased phosphorylation of p38 and Akt in the left ventricle after 1 and 4 weeks treatment, in association with reduced blood pressure and heart rate. Interestingly, the anti-hypertrophic, anti-fibrotic, and anti-inflammatory effects of moxonidine were observed with a sub-hypotensive dose (100µg/kg/h). These results suggest the beneficial cardiovascular effects of moxonidine associated with improved cardiac performance, regulation of inflammation by decreasing pro-inflammatory plasma levels, inhibition of p38 MAPK and Akt, and allow us to suggest that besides inhibiting the SNS, moxonidine may act on peripheral sites.