La rigidité artérielle ayant une valeur prédictive forte et indépendante d'évènements cardiovasculaires, nous émettons l'hypothèse que l'accumulation de variations de contraintes hémodynamiques altère la fonction et la structure des gros troncs artériels, indépendamment du niveau de pression artérielle. Nous avons donc mesuré l'impact de la variabilité tensionnelle sur la rigidité et la structure artérielles dans différents modèles de variabilité tensionnelle chez le rat.Chez le rat barodénervé et le rat sympathectomisé par la guanéthidine, 2 modèles de variabilité tensionnelle à court terme, une augmentation de la rigidité artérielle est associée à des altérations tissulaires différentes. En effet chez les rats barodénervés, une hypertrophie aortique est couplée à une augmentation du collagène et des attachements cellule-matrice (fibronectine et intégrine α5). Au contraire, chez les rats sympathectomisés, une hypotrophie vasculaire est associée à une diminution de l'élastine et une augmentation des attachements via l'intégrine αv.Nous avons ensuite créé, caractérisé et validé un modèle de variabilité tensionnelle à long terme, le rat spontanément hypertendu traité de façon discontinue par un antihypertenseur. Le traitement discontinu réduit la pression artérielle systolique tout en augmentant isolément la variabilité tensionnelle à long terme. La rigidité artérielle, élevée sous traitement discontinu, est associée à une hypertrophie vasculaire avec augmentation des attachements (fibronectine et intégrine αv) et sans modification du rapport élastine/collagène.En conclusion, l'élevation de variabilité tensionnelle engendre de la rigidité artérielle, et ce à pression artérielle constante. Les altérations structurales dans les modèles de variabilité tensionnelle étudiés impliquent des mécanismes différents reposant sur des modifications des relations cellule-matrice, mettant en jeu la fibronectine et les intégrines α5 et αv. / Arterial stiffness is nowadays accepted as a strong and independent predictor of cardiovascular disease. We hypothesized that increased blood pressure variability (BPV) may lead to arterial damage, independently of the blood pressure level. We thus aimed investigating the relationship between BPV and arterial stiffness and composition of the aorta in different rat models of increased BPV.In a first study performed in two models of increased short term BPV, sinoaortic denervated and chemically sympathectomized rats, an increase in wall stiffness was associated with different modifications of cell-extracellular matrix adhesion. Indeed in sinoaortic denervated rats, increased media cross-sectional area was coupled with an increased collagen content and muscle cell attachments to its cell-extracellular matrix (fibronectin and its α5β1 integrin). In contrast, chemically sympathectomized rats were characterized by a reduced media cross-sectional area associated to a reduction of elastin content and upregulation of αvβ3 integrin.In a second study, we created, characterized and validated a new experimental model of long term BPV by discontinuously treating spontaneously hypertensive rats with valsartan. Discontinuous treatment reduced systolic blood pressure level but increased long term BPV. In addition, this treatment regimen failed to reduce arterial stiffness and induced a vascular hypertrophy without modification of elastin/collagen ratio. Discontinuous treatment also highly increased vascular fibronectin in parallel to αv integrin.In conclusion, a rise of both short- and long-term BPV leads to an increase in arterial stiffness, independently of blood pressure level. The structural changes at the origin of this increase in arterial rigidity involve different mechanisms, in which fibronectin and integrin α5 and αv play a key role.

The aim of this dissertation was to address several gaps in the existing literature focused on the association between levels and variability in blood pressure (BP) and cognitive functioning. Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), Chapter 1 synthesizes and critically analyzes the outcomes of research reporting the association between BP variability (BPV) and cognition. Fifty-five studies met eligibility criteria, including reports measuring short-term, mid-term, and long-term BPV. Despite substantial between-study heterogeneity in study characteristics, the majority of studies reported that higher systolic BPV is associated with adverse cognitive outcomes. Further, Chapter 1 identified several gaps in the existing literature. For instance, no research has investigated the association between BPV and short-term fluctuations in cognitive functioning, or the association between mid-term BPV and concurrent cognitive functioning. Building on Chapter 1, Chapter 2 used an intensive measurement design to investigate the extent to which mid-term variability in BP, recorded using home-based BP monitoring, is associated with levels and variability in cognitive functioning in a sample of community-living older adults (N=64; Mage=70.58, SD=3.5; 77% female) assessed twice daily over a two-week period. Partial correlation coefficients estimated the association between BPV and variability in several ambulatory cognitive assessments, accounting for the learning effect during the study protocol, while multi-level models (MLMs) estimated the association between BPV and concurrent cognitive functioning. In addition, MLMs examined the extent to which BP and cognitive functioning fluctuate within and between days at the intraindividual and interindividual levels. Findings suggest that more BPV may be associated with slower or more variable reaction time, while higher BP may be associated with worse performance on accuracy tasks. / Graduate / 2022-08-30

Purpose: Evidence has accumulated to show that blood pressure variability (BPV) has a striking relationship with cardiovascular (CV) risk. Despite the mounting evidence implicating BPV as a CV risk factor, scant attention has been paid to: (1) the mechanisms by which high BPV confers greater CV risk; and (2) the efficacy of non-pharmacologic treatment modalities in the attenuation of BPV. In order to address these two unresolved questions, the purpose of this dissertation was twofold. The purpose of study #1 was to investigate the association between measures of short-term BPV (24-hour BPV) and long-term BPV (visit-to-visit BPV) with markers of endothelial health in a cohort of African Americans in order to determine if increased BPV may confer greater CV risk by eliciting injury to the endothelium. The purpose of study #2 was to investigate the effects of a 6-month aerobic exercise training (AEXT) intervention on visit-to-visit BPV and 24-hour BPV in the same cohort of African Americans in order to provide the first available data on the efficacy of a non-pharmacologic treatment modality in the lowering of BPV. Methods: We recruited 72 African Americans who were sedentary, non-diabetic, non-smoking, and free of CV and renal disease. Before and after a 6-month AEXT intervention, office blood pressure (BP) was measured at 3 separate visits and 24-hour ambulatory BP monitoring (ABPM) was conducted to measure visit-to-visit BPV and 24-hour BPV, respectively. Right brachial artery diameter was assessed at rest, during flow-mediated dilation (FMD), and after nitroglycerin-mediated dilation (NMD). Peak and area under the curve (AUC) were calculated as measures of FMD and NMD, and the FMD/NMD ratio was calculated as a measure of endothelial function normalized by smooth muscle function. Fasted blood samples were obtained and were analyzed for circulating EMPs expressed as CD31+CD42- and CD62E+ EMPs. Results: In study #1, participants with higher 24-hour diastolic BPV (DBPV) had significantly lower CD31+CD42- EMPs compared to participants with lower 24-hour DBPV. When categorized according to visit-to-visit DBPV, participants with higher visit-to-visit DBPV had a significantly lower FMD/NMD ratio, and significantly higher %NMDpeak and NMDAUCs compared to participants with lower visit-to-visit DBPV. When analyzed as continuous variables, 24-hour mean arterial pressure variability (MAPV) was inversely associated with CD31+CD42- EMPs visit-to-visit DBPV was inversely associated with the FMD/NMD ratio and positively associated with %NMDpeak and NMDAUC; and 24-hour DBPV was positively associated with NMDAUC. All associations were independent of age, gender, BMI, mean BP, and pulse pressure. In study #2 investigating the effects of AEXT in 33 participants who completed the study, 24-hour DBPV and 24-hour MAPV were significantly increased after AEXT. The increase in 24-hour DBPV was independent of changes in BMI, mean BP, and self-reported sleep time. Heart rate variability (HRV) derived from ABPM was associated with the changes in 24-hour DBPV and 24-hour MAPV. There were no significant changes in visit-to-visit BPV after AEXT. Conclusions: The results from study #1 provide evidence that BPV is associated with vascular health as endothelial function was decreased in participants with high visit-to-visit DBPV, while smooth muscle function was increased in participants with higher visit-to-visit and 24-hour DBPV. The findings from study #2 show that 6-months of AEXT do not elicit beneficial changes in BPV. The finding of an association between changes in 24-hour BPV with HRV could indicate, however, that changes in activity levels during ABPM, in part, contributed to the observed changes in 24-hour BPV. / Kinesiology

Barorezeptorsensitivität, Herzfrequenzvariabilität und Blutdruckvariabilität bei Patienten mit einem mild-moderaten Schlafapnoe Syndrom und bei gesunden Probanden Die Behandlung von Patienten mit einem mild-moderaten obstruktiven Schlafapnoe Syndrom (OSAS) wird von der klinischen Symptomatik und dem Herzkreislaufrisiko bestimmt. Wir konnten nachweisen, dass bei einem mild-moderaten OSAS unter der Beatmungstherapie neben der Beseitigung der nächtlichen Atmungsstörung auch eine Änderung der Mikrostruktur des Schlafes (Arousal) und der Müdigkeit am Tage zu verzeichnen ist. Das Herzkreislaufrisiko untersuchten wir anhand noninvasiver Parameter der sympathovagalen Balance. Dazu wurden die Herzfrequenzvariabilität (HRV), die Blutdruckvariabilität (BDV) und die Barorezeptorsensitivität (BRS) im Zeit- und Frequenzbereich bestimmt und diese Größen bei Patienten mit einem mild-moderaten OSAS im Vergleich zu gesunden Probanden als auch der Effekt einer CPAP-Therapie - im Schlaf als auch am Tage - analysiert. Bei gesunden Probanden fanden wir eine HRV- und BRS-Abnahme sowie eine BDV-Zunahme im REM- gegenüber dem NREM-Schlaf. OSAS Patienten haben im Vergleich zu Gesunden eine niedrigere BRS im NREM und eine erhöhte BDV sowohl im REM- als auch NREM-Schlaf. CPAP führt beim OSAS zu einer Abnahme der Herzfrequenz und Zunahme der BRS, vornehmlich im NREM Schlaf und bei zusätzlich bekannter Hypertonie. Die HRV nimmt ab und die BDV zu, jeweils unabhängig vom Schlafstadium bzw. einer bestehenden Hypertonie. Am Tage zeigt sich nur ein Kurzzeiteffekt hinsichtlich Zunahme der BRS und HRV. Dieser Effekt ist vom Ausmaß des OSAS und dem Vorhandensein einer Hypertonie abhängig und nach 4 Wochen Therapie nicht mehr nachweisbar. Untersucht man den Effekt der Beatmungstherapie auf HRV, BDV und BRS bei gesunden Probanden im Akutversuch, dann findet man eine Erhöhung des Blutdruckes bei Abnahme der Herzfrequenz und Zunahme der BRS. HRV, BDV und BRS als Parameter für das kardiovaskuläre Risiko zeigen nachweisbare Veränderungen bei Schlafapnoe Patienten, auch wenn nur ein mild-moderates OSAS vorliegt. Ein Therapieeffekt lässt sich anhand dieser Parameter auch nachweisen, wobei ein vorhandener Akuteffekt von Überdruckbeatmung auf HRV, BDV und BRS unabhängig von einem OSAS zu berücksichtigen ist. / Baroreceptor sensitivity, heart-rate variability, and blood-pressure variability in patients with mild to moderate sleep apnoea syndrome, and in healthy controls The treatment of patients with mild to moderate obstructive sleep apnoea syndrome, OSAS, is determined by the clinical symptom complex and by the cardiovascular risk. In patients with mild to moderate OSAS who received therapy in the form of assisted ventilation, we succeeded in evidencing that it is possible to influence the microstructure of sleep (i.e., of arousal) as well as fatigue experienced during the day, in addition to eliminating nocturnal respiratory disturbance. We investigated the cardiovascular risk by examining non-invasive parameters for sympathovagal balance. Therefore we analyzed heart-rate variability (HRV), blood-pressure variability (BPV), and baroreceptor sensitivity (BRS) over time and frequency ranges in patients with mild to moderate OSAS, in comparison to healthy controls. We likewise assessed the effects of CPAP therapy on these parameters, both during sleeping as well as non-sleeping hours. Among healthy test subjects, we determined decreases in HRV and BRS, as well as increase in BPV, during REM sleep, in comparison to NREM sleep. In comparison to healthy controls, OSAS patients have lower BRS during NREM and increased BPV in both REM and NREM sleep. In OSAS patients, CPAP leads to a decrease in heart rate and increase in BRS, especially in NREM sleep and in patients for whom hypertension is also known. HRV diminishes and BPV increases, in both cases regardless of the sleep stage or presence or absence of hypertension. During the day, only a short-term effect becomes apparent with respect to increases in BRS and HRV. This effect depends on the extent of OSAS and on the existence of hypertension; after four weeks of therapy, the effect is no longer in evidence. Acute testing of the effect of assisted ventilation on HRV, BPV, and BRS among healthy controls discloses increase in blood pressure, accompanied by decrease in heart rate and increase in BRS. HRV, BPV, and BRS as parameters for cardiovascular risk reveal evidence of alterations in sleep-apnoea patients, even for those suffering only from mild to moderate OSAS. Therapeutic effects are also in evidence on the basis of these parameters, whereby an existing acute effect of positive-pressure ventilation on HRV, BPV, and BRS regardless of OSAS must also be taken into account.

In this thesis, we included results from two studies. The first one considered the effects of the blood volume changes, during blood donation, on the heart rate variability (HRV) measured, non-invasively, form electrocardiographic (ECG) and photoplethysmographic (PPG) signals. Our results showed that, during blood donation, there were no significant changes in the pulsatile area of PPG signal, while heart rate increased. No significant changes were noticed in HRV extracted from both signals. Error analysis between the HRV extracted from ECG and peak interval variability (PIV) suggested that the error during blood donation was increased which means that the use of PIV extracted from PPG signal, used as a replacement diagnostic tool in clinical applications, needs further investigations and should be carefully studied in non-stationary cardiovascular situations such as blood donation. The imbalance between the two branches of the autonomic nervous system, sympathetic and parasympathetic, vagal, may result in a harmful activation of myocardial tissues which cause arrhythmias and sudden cardiac death. Although the study of the sympathovagal balance have been attracting many researchers, further studies are needed to elucidate the effects of many kinds of drugs on the autonomic modulation of the cardiac muscle, specifically, the cells of sinoatrial (SA) node. The aim of the second part of this thesis was to assess the effects of calcium channel blocker (Verapamil), calcium channel sensitizer (Levosimendan), calcium chloride (CaCl2), the combinations of verapamil/ CaCl2, levosimendan/ CaCl2, and noradrenaline infusion on beat-to-beat cardiovascular variability represented, in this research, by systolic blood pressure variability (SBPV), and stroke volume variability (SVV) signals. We used Fat Fourier Transform (FFT) to evaluate the power spectral density of the fluctuations in both signals to evaluate the effects of short-term treatments with those drugs on the sympathovagal balance in normal rats. Then, we compared the spectra obtained from SBPV and SVV to decide which of these fluctuations along with corresponding spectrum was more able to provide a clear feedback about the autonomic nervous system. Our data suggests that there were a significant correlations between low- (LF), mid- (MF), and high-frequency (HF) spectra obtained from SBPV and SVV except between the HF spectra estimated from after the infusion of levosimendan where a poor correlation (r = 0.530, p = 0.281) was noticed. This that both HF components obtained provide different information regarding the autonomic nervous system modulation of the SA node cells, while the results obtained from the rest of experiments showed that both signals provide same information about the modulation of sympathetic and parasympathetic tone due to all stages of different drugs infusion studied in this thesis. Besides that, we found that both spectra may be used to track the fluctuations in the cardiac output as a result of the drugs infusion.

In this thesis, we included results from two studies. The first one considered the effects of the blood volume changes, during blood donation, on the heart rate variability (HRV) measured, non-invasively, form electrocardiographic (ECG) and photoplethysmographic (PPG) signals. Our results showed that, during blood donation, there were no significant changes in the pulsatile area of PPG signal, while heart rate increased. No significant changes were noticed in HRV extracted from both signals. Error analysis between the HRV extracted from ECG and peak interval variability (PIV) suggested that the error during blood donation was increased which means that the use of PIV extracted from PPG signal, used as a replacement diagnostic tool in clinical applications, needs further investigations and should be carefully studied in non-stationary cardiovascular situations such as blood donation. The imbalance between the two branches of the autonomic nervous system, sympathetic and parasympathetic, vagal, may result in a harmful activation of myocardial tissues which cause arrhythmias and sudden cardiac death. Although the study of the sympathovagal balance have been attracting many researchers, further studies are needed to elucidate the effects of many kinds of drugs on the autonomic modulation of the cardiac muscle, specifically, the cells of sinoatrial (SA) node. The aim of the second part of this thesis was to assess the effects of calcium channel blocker (Verapamil), calcium channel sensitizer (Levosimendan), calcium chloride (CaCl2), the combinations of verapamil/ CaCl2, levosimendan/ CaCl2, and noradrenaline infusion on beat-to-beat cardiovascular variability represented, in this research, by systolic blood pressure variability (SBPV), and stroke volume variability (SVV) signals. We used Fat Fourier Transform (FFT) to evaluate the power spectral density of the fluctuations in both signals to evaluate the effects of short-term treatments with those drugs on the sympathovagal balance in normal rats. Then, we compared the spectra obtained from SBPV and SVV to decide which of these fluctuations along with corresponding spectrum was more able to provide a clear feedback about the autonomic nervous system. Our data suggests that there were a significant correlations between low- (LF), mid- (MF), and high-frequency (HF) spectra obtained from SBPV and SVV except between the HF spectra estimated from after the infusion of levosimendan where a poor correlation (r = 0.530, p = 0.281) was noticed. This that both HF components obtained provide different information regarding the autonomic nervous system modulation of the SA node cells, while the results obtained from the rest of experiments showed that both signals provide same information about the modulation of sympathetic and parasympathetic tone due to all stages of different drugs infusion studied in this thesis. Besides that, we found that both spectra may be used to track the fluctuations in the cardiac output as a result of the drugs infusion.

Made available in DSpace on 2016-06-02T20:19:25Z (GMT). No. of bitstreams: 1 6555.pdf: 1289563 bytes, checksum: 019c580e1b818068847725c1d7aeadfa (MD5) Previous issue date: 2015-02-05 / Universidade Federal de Minas Gerais / Frailty is related to a decrease in the physiological reserves that causes a difficult to maintain homeostasis. The analysis of heart period (HP) and blood pressure (BP) variabilities can contribute to the understanding of cardiovascular homeostasis in the frailty syndrome. Objective: To compare HP and BP variabilities in frail, prefrail and nonfrail, un supine and orthostatic positions, by univariate and bivariate analysis. Methods: 39 elderly were evaluated and distributed in frail, prefrail and nonfrail groups, accordingly to frailty phenotype. The RR interval (RRi) and the systolic BP (SBP) series were registered for 15 minutes in the supine position and 15 minutes in orthostatic position. Univariate analysis (RRi: mean, variance, LFnu, HFabs and LF/HF and the SBP: mean, variance and LFabs) and bivariate analysis (phase, gain (α) and coherence (K2)) were performed. A two-way repeated measures ANOVA test was used for the statistical analysis; a 5% significance level was considered, along with group, position and interaction effects. Results: Univariate analysis do not detected changes in frailty syndrome. However, in the bivariate analysis frail presented lower K² than nonfrail in orthostatic position. Prefrail and frail reported a significant decrease in K² values in orthostatic position in comparison to the supine. Conclusion: Univariate analysis of HP and BP variabilities do not change when frailty syndrome is present. However, bivariate analysis indicated decoupling between HP and BP in frailty presence. Thus, a reduced K2 might be a marker of frailty process. / A fragilidade está associada à redução das reservas fisiológicas que leva à dificuldade na manutenção da homeostase. A análise da variabilidade da frequência cardíaca (FC) e da pressão arterial (PA) pode contribuir para a compreensão da homeostase cardiovascular na síndrome da fragilidade. Objetivo: Comparar a variabilidade da frequência cardíaca (VFC) e a variabilidade da pressão arterial sistólica (VPA) de indivíduos frágeis, pré-frágeis e robustos, nas posturas supina e ortostática, utilizando-se de análises univariada e bivariada. Métodos: Foram avaliados 39 idosos, alocados em 3 grupos de acordo com o fenótipo da fragilidade. As séries de intervalos RR (iRR) e de PA sistólica (PAS) foram registradas por 15 minutos em repouso na posição supina, e 15 minutos na posição ortostática. Foram realizadas as análises univariada (iRR: média, variância, baixa frequência em unidades normalizadas (BFun), alta frequência em unidades absolutas (AFabs) e razão entre a baixa e alta frequência (BF/AF) e PAS: média, variância e BFabs) e bivariada (fase, ganho (α) e coerência (K2)). Para análise estatística foi utilizado o teste Anova two way de medidas repetidas, com efeitos de grupo, posição e interação entre estes, considerando um nível de significância de 5%. Resultados: A análise univariada não detectou alterações na síndrome da fragilidade. Entretanto, na análise bivariada os frágeis apresentaram menores valores de K2 em comparação aos robustos na posição ortostática. Préfrágeis e frágeis apresentaram redução significativa nos valores de K2 na posição ortostática em comparação à supina. Conclusão: A variabilidade da FC e da PA, avaliada pela análise univariada, não se altera quando a fragilidade está presente. Por sua vez, a análise bivariada indicou um maior desacoplamento entre FC e PA na presença da síndrome da fragilidade. Desta forma, a K2 reduzida pode ser um marcador do processo de fragilização.

An autonomic dysfunction caused by spinal cord injury may have a significant impact on quality of life, especially in cases of lesions occuring above the sixth spinal segment. In these cases also cardiovascular system control is damaged in a different extent, which is subsequently presented by e.g. persisting bradycardia, heart frequency inadequate reaction to strain and stress or by huge variations of blood pressure values, which the situation complicate even more. The fact that cardiovascular diseases take now the frontmost place in causes of mortality of people with spinal cord injury is another evidence how important this topic is. The main aim of my thesis was to describe impacts of autonomic injury on cardiovascular functions and to try to objectify them using heart rate and blood pressure variability. Twenty-one patients of Motol University Hospitalv Spinal Unit with spinal cord lesion above Th6 segment and ten healthy people as a control group participated in the study. We created suitable conditions for highlighting disrupted cardiovascular functions of urgent spinal patients by modification of the standardized Head Up Tilt Test (HUTT). The heart rate and blood pressure values were continuously monitored by Finapres device before, during and also after verticalization on a tilt table....

A síncope neurocardiogênica (SNC) é caracterizada por perda transitória da consciência e do controle postural, devido a uma hipoperfusão cerebral global de surgimento abrupto, com recuperação rápida e espontânea do paciente ao retornar à posição horizontal. Entretanto, investigações adicionais são necessárias para melhor avaliação das respostas cardiorrespiratórias e autonômicas de pacientes com SNC submetidos ao Tilt-test. O presente estudo teve como objetivo avaliar, em pacientes com história clínica sugestiva de SNC, os efeitos da mudança postural induzidas pelo Tilt-test na pressão arterial (PA) e frequência cardíaca (FC), na variabilidade cardiocirculatória e na sensibilidade barorreflexa (SBR). Além disso, o estudo também avaliou a relação entre a idade, sexo e características antropométricas dos pacientes com as respostas ao Tilt-test, e a relação entre o tempo do início da mudança postural e o momento da síncope, com um ou mais parâmetros acima mencionados. O estudo foi dividido em 3 partes: 1 Estudo retrospectivo de 180 pacientes, com história clínica sugestiva de SNC, mas que apresentaram Tilt-test positivo (TTP) (128 indivíduos) ou negativo (TTN) (52 indivíduos) para síncope; 2 Estudo da variabilidade da frequência cardíaca (VFC), usando-se métodos lineares (Transformada Rápida de Fourier) em pacientes com história clínica sugestiva de SNC, e com respostas positiva ou negativa ao Tilt-test. Foram incluídos 62 pacientes, 31 com Tilt-test positivo e 31 negativo; 3 Estudo da variabilidade da pressão arterial sistólica (VPAS), usando-se métodos lineares (Transformada Rápida de Fourier), e da SBR (Método da Sequência) em pacientes com história clínica sugestiva de SNC, e com respostas positiva ou negativa ao Tilt-test. Foram estudados 33 indivíduos, 16 com Tilt-test positivo e 17 negativo. Estudo 1 Observou-se que a incidência de SNC foi 1,5 vezes maior em mulheres do que em homens. Além disso, os grupos TTP e TTN apresentaram idade e características antropométricas semelhantes entre si, e não houve significância estatística nas correlações entre o tempo do início da posição vertical até a síncope, a idade e as características antropométricas. Estudo 2 Comparando os 2 grupos nos domínios do tempo (SD-iRR, variância-iRR, RMSSD) e da frequência (LF (un), HF (un) e LF/HF) nas fases Pré-Tilt, Tilt e Pós-Tilt, com exceção do iRR (ms), não observou-se diferença entre os grupos. Houve, na fase Tilt, um menor valor do iRR no grupo TTP. O Pré-Tilt comparado ao Tilt, promoveu em ambos os grupos redução do iRR e aumento na razão LF/HF. Estudo 3 Comparando-se os grupos TTP e TTN no Pré-Tilt e Tilt, não houve diferença no LF da PAS e na SBR. O Tilt promoveu, em ambos os grupos, aumento no LF da PAS, redução na SBR. Somente no grupo TTP foi observado aumento no desvio padrão da PAS durante o Tilt. Em conclusão, o estudo 1 demonstrou que a SNC não foi influenciada pela idade e características antropométricas, no que diz respeito à prevalência, e ao tempo de duração entre o início da mudança postural no Tilt-test e o momento do aparecimento da síncope na posição vertical. O estudo 2 demonstrou que indivíduos com suspeita clínica de SNC, e Tilt-test positivo ou negativo não apresentam anormalidades no balanço simpato-vagal cardíaco, mas, apresentaram diferenças no iRR. O estudo 3 não evidenciou diferenças no controle autonômico cardiovascular (LF-PAS e SBR) entre os grupos TTP e TTN no Pré-Tilt e Tilt. Os estudos 2 e 3 mostraram que com a metodologia utilizada na análise da VFC e VPAS não foi possível detectar anormalidades significativas da modulação autonômica cardiovascular nos grupos TTP e TTN, e desse modo, prever na posição vertical do Tilttest, se um paciente com história clínica sugestiva de SNC apresentará ou não síncope. / Neurocardiogenic syncope (NCS) is characterized by transient loss of consciousness and postural control, due to abrupt global cerebral hypoperfusion, with rapid and spontaneous recovery after changing the patient to horizontal position. However, further investigations are necessary to better understand the cardiorespiratory and autonomic responses to the Tilt-test in NCS patients. The present study aimed to evaluate, in patients with a history suspicion of NCS, the effects of postural change (Tilt-test) on blood pressure (BP) and heart rate (HR), on the cardiovascular variability and baroreflex sensitivity (BRS). Furthermore, the study also assessed the relationship between age, sex and anthropometric characteristics with the Tilt-test responses, and the relationship between the time period taken to experience syncope following postural change and the above cited parameters. The study was divided into three parts: 1 A retrospective study with 180 patients with a history suspicion of NCS, that experienced (TTP; 128 individuals) or not (TTN; 52 individuals) syncope following Tilt-test; 2 A study of the heart rate variability (HRV), assessed by linear methods (Fast Fourier Transform), in patients with a history suspicion of NCS and that experienced, or not, syncope following Tilt-test. The study included 62 patients (31 in TTP group and 31 in TTN group); 3 A study of the systolic blood pressure variability (SAPV), using linear methods (Fast Fourier Transform), and of the BRS (Sequence Method) in patients with a history compatible with NCS and that experienced, or not, syncope following Tilt-test. The study included 33 patients (16 in TTP group and 17 in TTN group). Study 1 it was observed that the incidence of NCS was 1.5 times greater in women than in men. Furthermore, groups TTP and TTN showed age and anthropometric characteristics similar to each other and no statistical significance was observed in the correlations among the time period taken to experience syncope following postural change and age and anthropometric characteristics. Study 2 The analysis of the cardiovascular variability, by means of time (SD-iRR, variance-iRR, RMSSD) and frequency (LF (nu), HF (nu) and LF/HF) domain methods, revealed no differences between groups in the Pre-Tilt, Tilt and Post-Tilt phases. However, iRR (ms) was found different between groups. During the Tilt phase, TTP group has shown lower iRR as compared to TTN. Also, TTP and TTN groups exhibited lower iRR and higher LF/HF ratio during Tilt-test as compared to Pre-Tilt phase. Study 3 Comparing the TTP and TTN groups, no statistical differences were found in the LF power of SAP and BRS in both Pre-Tilt and Tilt phases. Following Tilt-test it was observed an increase in LF power of SAP and a reduction in BRS. TTP group showed higher SAP standard deviation during the Tilt phase. In conclusion, study 1 demonstrated that NCS incidence and the time period taken to experience syncope following postural change were not influenced by age and anthropometric characteristics. Study 2 has shown that patients with a history suspicion of NCS, that experienced or not syncope following Tilt-test do not show abnormalities in the sympatovagal balance, but exhibited changes in the iRR. Study 3 showed that the cardiovascular autonomic control (LF-SAP and BRS) is not different between the TTP and TTN groups, in the Pre-Tilt and Tilt phases. Studies 2 and 3 have shown that the methods employed in the analysis of HRV and SAPV were unable to reveal abnormalities in the cardiovascular autonomic modulation in TTP and TTN groups, and thus, can not predict if a patient with a history suspicion of NCS will experience or not syncope during Tilt-test.

INTRODUÇÂO: A hipertensão arterial sistêmica (HAS) é uma condição clínica com alta prevalência, sendo considerada como o principal fator de risco modificável para o desenvolvimento de insuficiência cardíaca (IC). Dentre os mecanismos relacionados à progressão da HAS para a IC, a hiperatividade simpática e a disfunção endotelial devem ser consideradas. OBJETIVO: Avaliar a modulação do sistema nervoso autônomo (central e periférico), e a função endotelial em pacientes hipertensos com diferentes graus de disfunção diastólica (DD) do ventrículo esquerdo (VE). CASUÍSTICA E MÉTODO: Quarenta e cinco pacientes com HAS, sem outras co-morbidades foram submetidos ao exame de ecoDopplercardiograma tecidual, e foram alocados em três grupos: (GHT) sem alteração funcional ou estrutural cardíacas (n=15, 7 homens, 48±2 anos, IMC 28±1 Kg/m2), (GDD-ar) com diagnóstico prévio de IC diastólica e com DD padrão alteração de relaxamento do VE (n=15, 7 homens, 53±2 anos, IMC 29±1 Kg/m2) e (GDD-pr) com diagnóstico prévio de IC diastólica com padrão pseudonormal ou restritivo de DD do VE (n=15, 9 homens, 51±2 anos, IMC 27±1 Kg/m2). Voluntários saudáveis normotensos (n=14, grupo GNT) pareados para idade, sexo e IMC também foram avaliados. Curvas de pressão arterial (PA) foram registradas de modo contínuo e não invasivo (Finometer®) durante 15 minutos em repouso, na posição supina. Simultaneamente, a atividade nervosa simpática muscular (ANSM) foi registrada por meio da técnica de microneurografia. A variabilidade da freqüência cardíaca (VFC) e da pressão arterial sistólica (VPAS) foi estimada pelo método FFT. Em um segundo momento foi realizada a avaliação da função endotelial, por meio de ultrassonografia da artéria braquial associada à manobra de hiperemia reativa e após administração de trinitrato sublingual. As análises estatísticas foram realizadas pelo teste exato de Fisher e ANOVA, os resultados expressos em média ± erro padrão ou em mediana (valores mínimos e máximos). RESULTADOS: Não houve diferenças de gênero, idade e IMC entre os grupos, como também no uso das diferentes classes de drogas anti-hipertensivas entre os hipertensos. Os parâmetros estruturais cardíacos foram semelhante entre os grupos, com exceção da massa de VE do grupo GDD-pr [98 (66-162) g/m2] foi maior, p<0,05, quando comparada ao grupo GNT [85 (56-95) g/m2]. A PA sistólica (PAS) não foi diferente entre GHT, GDD-ar e GDD-pr [(138 (110-149), 133 (104-190) e 148 (118-171) mmHg, respectivamente]. Os grupos GDD-ar e GDD-pr apresentaram PAS maiores, p<0,05,quando comparados ao grupo GNT [121(108-133) mmHg]. A PA diastólica foi semelhante entre os grupos. Os grupos mostraram semelhantes valores para a modulação autonômica cardíaca avaliada pela VFC. A modulação simpática periférica representada pelo componente LF PAS da VPAS (mmHg2) foi aumentada nos grupos GDD-ar (12,2±1,3) e GDD-pr (11,7±1,2) quando comparados ao grupo GNT (6,7±0,6), p<0,05, mas não quando comparada ao grupo GHT (9,3±1,1). O prejuízo baroreflexo (índice alfa LF, ms/mmHg) foi observado nos grupos GDD-ar (4,6±0,6) e GDD-pr (5,07±0,7) quando comparados ao grupo GNT (8,2±1), p<0,05, mas não quando comparados ao grupo GHT (6,05±0,5). ANSM (espículas/min) foi maior significativamente nos grupos GDD-ar (33±1) e GDD-pr (32±1) quando comparada aos grupos GHT (26±1) e GNT (15±1) p<0,05. Ainda, o grupo GHT apresentou aumento da ANSM quando comparado ao grupo GNT, p<0,05. Os grupo GDD-ar e GDD-pr apresentaram valores semelhantes de ANSM. Com relação à avaliação da função endotelial, os grupos hipertensos apresentaram menor dilatação dependente do endotélio, sendo que somente no grupo GDD-ar [0,67 (0,0-8,7)%] houve significância estatística quando comparado ao GNT [6,3 (2,6-8,2)%]. Na avaliação da vasodilatação independente do endotélio os grupos apresentaram respostas semelhantes. CONCLUSÃO: A presença de disfunção diastólica, em qualquer grau, está associada à maior ANSM e modulação simpática periférica (LF PAS) e a menor sensibilidade do baroreflexo. A modulação simpática cardíaca não apresentou diferença entre os grupos em repouso. Outros estudos são necessários para esclarecer a relação entre causa - efeito de tais achados / INTRODUTION: The hypertension (HP) is a clinical condition with high prevalence, considered as a main modifiable risk factor for developing heart failure (HF). Among the mechanism related to the progression for HP to the HF, the sympathetic hyperactivity and endothelial dysfunction should be considered. OBJECTIVE: Evaluate the autonomic nervous system modulation (central and peripheral), and endothelial function in hypertensive patients with different pattern of diastolic dysfunction (DD) of the left ventricle (LV). METHOD: Forty-five hypertensive patients without comorbities were submitted to tissue Doppler echocardiography and allocated into three groups: (GHT) without cardiac functional or structural abnormalities (n=15, 7 men, 48±2 years, BMI 28±1 Kg/m2); (GDD-ar) with prior diastolic HF and impaired relaxation pattern of DD of LV (n=15, 7 men, 53±2 years, BMI 29±1 Kg/m2), and (GDD-pr) with prior diastolic HF and pseudonormal and restrictive patterns of DD of LV (n=15, 9 men, 51±2 years, BMI 27±1 Kg/m2). Normotensive healthy volunteers matched for age, sex and body mass index were also evaluated. Curves of blood pressure (BP) were recorded non-invasively and continuously (Finometer®) for 15 minutes at rest in the supine position. Simultaneously, muscle nerve sympathetic activity (MNSA) was recorded by microneurography technique. The heart rate and systolic blood pressure variability (HRV and SPBV) was estimated by FFT method. Afterwards, an evaluation of endothelial function through brachial artery ultrasound maneuver associated with reactive hyperemia and after sublingual administration of trinitrate was conducted. Statistical analysis was performed by Fishers exact test and ANOVA, the results are expressed as mean±standard deviation or median (minimum and maximum values). RESULTS: There were no differences in gender, age and BMI between the groups, as well as in the use of different classes of antihypertensive drugs among hypertensive patients. Cardiac structural parameters were similar between groups, except for LV mass in GDD-pr group [98 (66-162) g/m2] which was higher, p<0.05, when compared to the GNT group [85 (56-95) g/m2]. The systolic blood pressure (SBP) was similar between GHT, GDD-ar and GDD-pr groups [(138 (110-149), 133 (104-190) e 148 (118-171) mmHg, respectively]. The GDD-ar and GDD-pr groups had higher SBP, p<0.05, when compared to GNT group [121(108-133) mmHg]. The diastolic BP was similar between groups. The groups showed similar values for cardiac autonomic modulation assessed by HRV. The peripheral sympathetic modulation represented by the LF component of SBP (SBPV, mmHg2) was increased in GDD-ar group (12,2±1,3) and GDD-pr group (11,7±1,2) compared to the GNT group (6,7±0,6), p<0.05, but not when compared to GHT group (9,3±1,1). The impairment of the baroreflex (LF alpha índex, ms/mmHg) was observed in the GDD-ar (4,6±0,6) e GDD-pr (5,07±0,7) groups compared to the GNT group (8,2±1), p<0.05, but not when compared to GHT group (6,05±0,5). MNSA (burst/min) was significantly higher in GDD-ar (33±1) e GDD-pr (32±1) groups compared to GHT group (26±1) and GNT group (15±1) p<0.05. Also the GHT group showed increased MNSA when compared to GNT group, p<0.05. The GDD-ar and GDD-pr groups showed similar values of MNSA. Regarding the assessment of endothelial function, hypertensive groups had lower endothelium-dependent dilatation, but only in GDD-ar group [0,67 (0,0-8,7)%] was statistically significant when compared to GNT group [6,3 (2,6-8,2)%]. In the evaluation of endothelium-independent vasodilatation all groups showed similar responses. CONCLUSION: The presence of diastolic dysfunction of any pattern is associated with higher MNSA and peripheral sympathetic modulation (LF SBP) and lower sensitivity of the baroreflex. Cardiac sympathetic modulation did not differ between groups at rest. Further studies are needed to clarify the relationship between cause-effect of such findings