Cristiano Tavares

Lead toxicity promotes autonomic dysfunction with increased chemoreceptor sensitivity.

Mortality and morbidity by toxic metals is an important issue of occupational health. Lead is an ubiquitous heavy metal in our environment despite having no physiological role in biological systems. Being an homeostatic controller is expected that the autonomic nervous system would show a degree of impairment in lead toxicity. In fact, sympathoexcitation associated to high blood pressure and tachypnea has been described together with baroreflex dysfunction. However, the mechanisms underlying the autonomic dysfunction and the interplay between baro- and chemoreflex are not yet fully clarified. The angiotensinogenic PVN-NTS axis (paraventricular nucleus of the hypothalamus - nucleus tractus solitarius axis) is a particularly important neuronal pathway that could be responsible for the autonomic dysfunction and the cardiorespiratory impairment in lead toxicity. Within the current work, we addressed in vivo, baro- and chemoreceptor reflex behaviour, before and after central angiotensin inhibition, in order to better understand the cardiorespiratory autonomic mechanisms underlying the toxic effects of long-term lead exposure. For that, arterial pressure, heart rate, respiratory rate, sympathetic and parasympathetic activity and baro- and chemoreceptor reflex profiles of anaesthetized young adult rats exposed to lead, from foetal period to adulthood, were evaluated. Results showed increased chemosensitivity together with baroreceptor reflex impairment, sympathetic over-excitation, hypertension and tachypnea. Chemosensitivity and sympathetic overexcitation were reversed towards normality values by NTS treatment with A-779, an angiotensin (1-7) antagonist. No parasympathetic changes were observed before and after A-799 treatment. In conclusion, angiotensin (1-7) at NTS level is involved in the autonomic dysfunction observed in lead toxicity. The increased sensitivity of chemoreceptor reflex expresses the clear impairment of autonomic outflow to the cardiovascular and respiratory systems induced by putative persistent, long duration, alert reaction evoked by the long term exposure to lead toxic effects. The present study brings new insights on the central mechanisms implicated in the autonomic dysfunction induced by lead exposure which are relevant for the development of additional therapeutic options to tackle lead toxicity symptoms.

Reversing gene expression in cardiovascular target organs following chronic depression of the paraventricular nucleus of hypothalamus and rostral ventrolateral medulla in spontaneous hypertensive rats

BACKGROUND Chronic overexpression of an inwardly rectifying potassium channel (hKir2.1) in the paraventricular nucleus of the hypothalamus (PVN) and in the rostral ventrolateral medulla (RVLM) to suppress neuronal excitability, resulted in a long term decrease of blood pressure and sympathetic output in spontaneously hypertensive rats (SHR). OBJECTIVE Evaluate gene expression in end-organs of SHR after a chronic overexpression of hKir2.1 channels in either the PVN or RVLM. METHODS mRNA levels of 16 genes known to be involved with blood pressure regulation were evaluated using RT-PCR in tissues from the heart, common carotid artery and kidney of SHR submitted to chronic depression of PVN and RVLM excitability using a lentiviral vector (LVhKir2.1). RESULTS In SHR hearts in which either the PVN or RVLM were injected with LVhKir2.1, there was a downregulation of angiotensin II receptor 1b (AT1), ATPase, Ca(2+)-transporter, troponin T2 and tropomyosin2 (only in RVLM) relative to the sham group. In the kidney of SHR with LVhKir2.1 injections in PVN and RVLM, angiotensinogen, angiotensin II receptor2 (AT2) and endothelin1 were all upregulated compared to sham. In the carotid artery, endothelin2, endothelin receptor A and B were up-regulated following LVhKir2.1 in to either the PVN or RVLM relative to sham. CONCLUSION Chronic overexpression of hKir2.1 channels in PVN and RVLM, promoted a BP decrease with up-regulation of angiotensinogen and AT2 genes expression in the kidney and down-regulation of AT1 in the heart of SHR. Thus, we demonstrate the potential efficacy of central manipulation to protect against end-organ damage in essential hypertension.

An insight into the autonomic and haemodynamic mechanisms underlying reflex syncope in children and adolescents: a multiparametric analysis.

Around 15% of children and adolescents experience at least one episode of syncope until adulthood. Excluding cardiac disease, the majority of syncopes are of reflex origin and benign in nature. In this situation, a tilt test is conducted to reproduce symptoms and to evaluate cardiovascular adaptations to orthostatism, but its mechanisms are not yet well defined. Here, we investigated haemodynamics and autonomic activity during tilt in young patients. Patients (n=113) with unexplained syncope were enrolled. Tilt followed a standard protocol without provocative agents. A positive response (fainters) was defined as a sudden development of syncope or presyncope associated with hypotension, bradycardia, or both. Haemodynamic parameters, autonomic activity, and baroreflex sensibility were evaluated. Data were analysed on baseline; immediately after tilting; on tilt adaptation; before fainting or before tilt-down for non-fainters; and on tilt-down. A total of 45 patients experienced syncope after a mean time of 18 minutes. During tilting up, fainters showed lower blood pressure and peripheral resistance values, which decreased progressively with time together with baroreflex sensibility. Sympathetic tone increased massively along time till syncope. No changes in cardiac output and heart rate were observed. Results show a strong effort of the autonomic nervous system to adapt to orthostatic stress through different magnitudes of sympathetic output, which was maximal before syncope without apparent modifications of parasympathetic tone. These changes suggest an imbalance between both branches of the autonomic nervous system, not enabling a time-progressive adaptation and leading the subject to faint.

The arterial baroreflex effectiveness index in risk stratification of chronic heart failure patients who are candidates for cardiac resynchronization therapy.

INTRODUCTION Baroreflex function is an independent marker of prognosis in heart failure (HF). However, little is known about its relation to response to cardiac resynchronization therapy (CRT). The aim of this study is to assess arterial baroreflex function in HF patients who are candidates for CRT. METHODS The study population consisted of 25 patients with indication for CRT, aged 65±10 years, NYHA functional class ≥III in 52%, QRS width 159±15 ms, left ventricular ejection fraction (LVEF) 29±5%, left ventricular end-systolic volume (LVESV) 150±48 ml, B-type natriuretic peptide (BNP) 357±270 pg/ml, and peak oxygen consumption (peak VO2) 18.4±5.0 ml/kg/min. An orthostatic tilt test was performed to assess the baroreflex effectiveness index (BEI) by the sequence method. This group was compared with 15 age-matched healthy individuals. RESULTS HF patients showed a significantly depressed BEI during tilt (31±12% vs. 49±18%, p=0.001). A lower BEI was associated with higher BNP (p=0.038), lower peak VO2 (p=0.048), and higher LVESV (p=0.031). By applying a cut-off value of 25% for BEI, two clusters of patients were identified: lower risk cluster (BEI >25%) QRS 153 ms, LVESV 129 ml, BNP 146 pg/ml, peak VO2 19.0 ml/kg/min; and higher risk cluster (IEB ≤25%) QRS 167 ms, LVESV 189 ml, BNP 590 pg/ml, peak VO2 16.2 ml/kg/min. CONCLUSIONS Candidates for CRT show depressed arterial baroreflex function. Lower BEI was observed in high-risk HF patients. Baroreflex function correlated closely with other clinical HF parameters. Therefore, BEI may improve risk stratification in HF patients undergoing CRT.

Autonomic modulation in a patient with syncope and paroxysmal atrial-fibrillation

We report a case of a patient with recurrent syncope and paroxysmal atrial fibrillation whose clinical status greatly improved after a period of orthostatic training. The potential efficacy of this non-pharmacological measure in modulating the autonomic tone is discussed below.

A modified Hilbert-Huang algorithm to the assessment of heart rate variability

Heart rate variability is a classical method to quantify the autonomic outflow to the cardiovascular system. The current methods in frequency and time-frequency domains have shown some limitations in resolution. In this paper, we propose a modified Hilbert-Huang algorithm to the assessment of autonomic activity in heart rate signals. These approaches are evaluated while analyzing both simulated signals and experimental data from tachograms associated with cardiac autonomic blockade of patients with paroxysmal atrial fibrillation.

Original ArticleThe arterial baroreflex effectiveness index in risk stratification of chronic heart failure patients who are candidates for cardiac resynchronization therapyO índice de eficácia do barorreflexo na estratificação de risco de doentes com insuficiência cardíaca crónica candidatos à terapêutica de ressincronização cardíaca

Introduction Baroreflex function is an independent marker of prognosis in heart failure (HF). However, little is known about its relation to response to cardiac resynchronization therapy (CRT). The aim of this study is to assess arterial baroreflex function in HF patients who are candidates for CRT.

Application of a modified Hilbert-Huang Transform to autonomic evaluation in metabolic syndrome

The physiological signals are a challenge in terms of identification and processing due to its lack of stationarity and linearity. The autonomic output to the cardiovascular system is classically quantified by analysis of heart rate variability. The Fast Fourier Transform (FFT) and Discrete Wavelet Transform applied to the cardiac signals showed limitations in terms of time and frequency resolutions. With this work we propose the application of a Modified Hilbert-Huang Transform for tachogram and systogram evaluation with the introduction of a new method to smooth fluctuations endpoint. This work presents a comparative study using FFT and Hilbert-Huang methodologies. It is known that patients and animal models with diseases involving sympathoexcitation, eg.: Metabolic Syndrome (MetS), show increases in low frequencies band. Therefore, these mathematical tools are evaluated by analyzing experimental data from two animal species: MetS-rabbits (n=6) and MetS-rats (n=6) and their respective lean age and sex-matched controls (n=6 for each group). Modified Hilbert-Huang Transform analysis showed a sympathoexcitatory condition in MetS comparing to controls both in a rabbit and in a rat model of MetS. These significant differences on sympathetic tone were also confirmed by FFT but, the parasympathetic activity, was similar between normal and MetS animals. Results and its physiological interpretation clearly show the suitability of the modified Hilbert-Huang Transform as an alternative methodology for the dynamic assessment of the autonomic nervous system in MetS.

Reliability of a wearable system to evaluate ambulatory autonomic activity

Recent clinical research directs up to provide personalized health care, adapted to each patient and to his clinical situation. With this work, we showed that a wearable device with heart rate (HR), respiratory and temperature sensors could be used, under certain technical and environmental requirements, for a reliable autonomic evaluation outside the confinement of an autonomic laboratory.

Wavelet analysis of heart rate variability during microgravity simulation

Lately, heart rate variability (HRV) and blood pressure adaptations have been studied in relation to Space Exploration. Most data obtained so far, indicate a decrease in heart rate (HR), mainly explained by a decrease in the low frequency component (LF) of HRV and an increase in the high frequency band (HF), indicating a predominant vagal modulation during space flights. In order to validate our laboratory and in-house analysis software, as potential tools for space life sciences, 14 normal subjects participated in a 2 hours protocol of simulated weightlessness (HDT-6o) in addition to a Mental Stress Maneuver. All cardiac components were collected, and after wavelets analysis, preliminary results show a significant decrease in HR (p=0,0128). The LF/HF ratio shows a clear tendency to decrease, with a comprehensible increase in HF. During Mental Stress, HR was increased, correlating with higher LF, alongside a general decrease in HF. Overall, our preliminary results validate our laboratory, for studies in the field of human space physiology.