Academic literature on the topic 'Cardiovascular and autonomic response'

Introduction: Cigarette smoking is a prime risk factor for cardiovascular morbidity and mortality. Chronic smoking results in autonomic dysfunction leading to increased cardiovascular risk in smokers. The present study was planned to study the effect of smoking on the Cardiovascular Autonomic Functions among smokers. Materials and Methods: Fifty male subjects who were in the age group of 25 to 45 years. They were grouped into 25 smokers and 25 non-smokers. The participant subjects were selected among the staff members, residents and the patients from the routine OPD in SVIMS. Prior to study, they were informed about the procedure and the purpose of the study tests and written consents were obtained from them. The Cardiovascular Autonomic Function Tests were assessed by using a POLYGRAPH which was available in the department. Results and Conclusion: After applying the ‘t’-test for the difference between the two sample means, it was observed that there was a highly significant difference between the mean values of the BMI(i.e.p<0.01) and the para-sympathetic function tests among the smokers and the non – smokers(i.e.p<0.00). The Resting Heart Rate had significantly increased and the Deep breathing difference, the postural tachycardial index (Response to standing) and the Valsalva Ratio had significantly decreased in the smokers as compared to those in the non – smokers. After applying the ‘t’-test for the difference between the two sample means, it was observed that there was no significant difference between the mean values of the Postural hypotension test (i.e. p>0.05) and that there was a highly significant difference between the mean values of the Sustained handgrip test in the smokers and the non – smokers (i.e. p<0.00). KEY WORDS: Cardiovascular autonomic function tests, Smoking, Resting heart rate.

Sympathetic hyperactivity may be involved in primary hypertension. The purpose of this study was to evaluate both sympathetic and vagal activity responses in patients receiving amlodipine as antihypertensive agent. Patients and Methods. This prospective study included a group of primary hypertensive patients (N=32, mean age 54.6±7.6 years). The cardiovascular autonomic tests performed in this group, before and after 3 months of daily oral administration of amlodipine, included deep breathing, hand-grip, and mental stress tests. Statistical analysis was done using the Student’s t-test. Results. Cardiovascular autonomic reflexes responses before and after 3 months of amlodipine oral administration were as follows: the mental stress test stimulation method produced a central alpha adrenergic response of 23.9±8.7% versus 11.2±2.0% (P<0.05), a central beta sympathetic response of 16.7±9.2% versus 10.4±1.3% (P<0.05), a blood pressure increase in response to hand grip test of 20.5±7.3% versus 10.7±2.4% (P<0.05), vagal response to deep breathing test was 21.2±6.5% versus 30.8±2.9%, (P<0.05). Conclusion. The results attest that amlodipine may have an anti-sympathetic effect.

Motivation. There is growing interest in the use of cardiovascular variability indicators as measures of autonomic activity, even though reported results are not always comparable or as expected. This review aims to determine the consistency of results reported on the autonomic response to physical exercise as measured by heart rate variability, blood pressure variability and baroreceptor sensitivity. Method. An Ovid MEDLINE Database search for the period 1950 - March 2008 produced 46 articles for review. The published articles that evaluate the effect of exercise on the autonomic nervous system (ANS) are summarised in three categories: the response of the ANS during a bout of exercise, directly after exercise (recovery measurements), and after a long-term exercise programme. Results. Articles on the effect of training on the ANS as measured by cardiovascular variability indicators show increased variability, decreased variability, and no change in variability. Conclusion. Findings in this review emphasise that standardisation and refinement of these measuring tools are essential to produce results that can be repeated and used as reference. Standardisation is essential as these measurements are increasingly employed in studies regarding investigations of central autonomic regulation, those exploring the link between psychological pro cesses and physiological functioning, and those indicating ANS activity in response to exercise, training and overtraining. This review shows that important aspects are inter-individual differences, duration and intensity of the exercise programme, and choice and specific implementation of variability analysis techniques. South African Journal of Sports Medicine Vol. 20 (4) 2008: pp. 102-108

Motivation. There is growing interest in the use of cardiovascular variability indicators as measures of autonomic activity, even though reported results are not always comparable or as expected. This review aims to determine the consistency of results reported on the autonomic response to physical exercise as measured by heart rate variability, blood pressure variability and baroreceptor sensitivity. Method. An Ovid MEDLINE Database search for the period 1950 - March 2008 produced 46 articles for review. The published articles that evaluate the effect of exercise on the autonomic nervous system (ANS) are summarised in three categories: the response of the ANS during a bout of exercise, directly after exercise (recovery measurements), and after a long-term exercise programme. Results. Articles on the effect of training on the ANS as measured by cardiovascular variability indicators show increased variability, decreased variability, and no change in variability. Conclusion. Findings in this review emphasise that standardisation and refinement of these measuring tools are essential to produce results that can be repeated and used as reference. Standardisation is essential as these measurements are increasingly employed in studies regarding investigations of central autonomic regulation, those exploring the link between psychological pro cesses and physiological functioning, and those indicating ANS activity in response to exercise, training and overtraining. This review shows that important aspects are inter-individual differences, duration and intensity of the exercise programme, and choice and specific implementation of variability analysis techniques. South African Journal of Sports Medicine Vol. 20 (4) 2008: pp. 102-108

To determine the extent to which the autonomic nervous system modifies the fetal cardiovascular responses to exogenous norepinephrine (NE), NE was infused intravenously (0.39-39 micrograms/min) for 30 min into chronically catheterized sheep fetuses averaging 132 days gestation. The resulting changes in arterial pressure, venous pressure, heart rate, and blood volume were compared between fetuses with and without ganglionic blockade. Autonomic blockade did not alter the relationship between the rise in NE concentration and NE infusion rate. In fetuses with a blocked autonomic nervous system, the arterial pressure response to exogenous NE was shifted 0.8 log units to the left when compared with normal fetuses. The venous pressure response to NE infusion was not altered in the blocked fetuses when compared with normal fetuses. Heart rate in the autonomically blocked fetuses increased with plasma NE concentration, which was opposite to the initial suppression of heart rate during NE infusion in control fetuses. Fetal blood volume decreased progressively with increasing NE infusion rate in the blocked fetuses, which was similar in autonomically intact fetuses, except for an increase in blood volume at low NE infusion rates. Thus it appears that the autonomic nervous system modifies the fetal arterial pressure, heart rate, and blood volume responses to exogenous NE but not the response of venous pressure

Introduction Migraine and vasovagal syncope are comorbid conditions that may share part of their pathophysiology through autonomic control of the systemic circulation. Nitroglycerin can trigger both syncope and migraine attacks, suggesting enhanced systemic sensitivity in migraine. We aimed to determine the cardiovascular responses to nitroglycerin in migraine. Methods In 16 women with migraine without aura and 10 age- and gender-matched controls without headache, intravenous nitroglycerin (0.5 µg·kg−1·min−1) was administered. Finger photoplethysmography continuously assessed cardiovascular parameters (mean arterial pressure, heart rate, cardiac output, stroke volume and total peripheral resistance) before, during and after nitroglycerin infusion. Results Nitroglycerin provoked a migraine-like attack in 13/16 (81.2%) migraineurs but not in controls ( p = .0001). No syncope was provoked. Migraineurs who later developed a migraine-like attack showed different responses in all parameters vs. controls (all p < .001): The decreases in cardiac output and stroke volume were more rapid and longer lasting, heart rate increased, mean arterial pressure and total peripheral resistance were higher and decreased steeply after an initial increase. Discussion Migraineurs who developed a migraine-like attack in response to nitroglycerin showed stronger systemic cardiovascular responses compared to non-headache controls. The stronger systemic cardiovascular responses in migraine suggest increased systemic sensitivity to vasodilators, possibly due to insufficient autonomic compensatory mechanisms.

Autonomic cardiovascular responses and the change in renal sympathetic nerve activity (RSNA) in response to smoke exposure were investigated in unrestrained conscious rats. Smoke exposure caused a prominent increase in RSNA (to 557.3 +/- 221.9% of the control level) and plasma norepinephrine [from 0.18 +/- 0.08 (control) to 0.66 +/- 0.22 ng/ml (at peak response of smoke exposure)], a slight increase in arterial blood pressure (from 89.6 +/- 3.3 to 103.6 +/- 3.8 mmHg), and marked bradycardia (from 386.6 +/- 12.8 to 231.3 +/- 20.6 beats/min). Respiratory rate in conscious rats was initially increased (from 1.6 +/- 0.1 to 6.1 +/- 0.3 breaths/s) but was decreased (to 0.9 +/- 0.1 breaths/s) at the peak phase of the cardiovascular responses to smoke inhalation. Blood gases and pH reflected these changes in respiratory rate to some extent. Sinoaortic denervation did not attenuate the bradycardia (from 402 +/- 17.5 to 255.8 +/- 16.2 beats/min) or increase in RSNA (to 413.4 +/- 74.9%) that occurred during smoke inhalation. Atropine sulfate abolished the bradycardic response (from 440.4 +/- 13.8 to 485.4 +/- 8.6 beats/min). Initial tachypnea was also observed in both sinoaortic denervated rats and atropine-treated rats. Anesthesia, induced by pentobarbital sodium (30 mg/kg iv) or alpha-chloralose (65 mg/kg iv), abolished the bradycardia, the increase in RSNA, and the change in respiratory rate caused by smoke exposure. Ablation of the olfactory lobes also greatly attenuated the smoke-induced increase in RSNA (to 150.9 +/- 22.9%), bradycardia (from 372.9 +/- 19.6 to 376.3 +/- 24.1 beats/min), and the respiratory change.(ABSTRACT TRUNCATED AT 250 WORDS)

Introduction. Diabetes is strongly associated with macrovascular complications, among which ischemic heart disease is the major cause of mortality. Autonomic neuropathy increases the risk of complications, which calls for an early diagnosis. The aim of this study was to determine both presence and extent of cardiac autonomic neuropathy, in regard to the type of diabetes mellitus, as well as its correlation with coronary disease and major cardiovascular risk factors. Material and methods. We have examined 90 subjects, classified into three groups, with 30 patients each: those with type 1 diabetes, type 2 diabetes and control group of healthy subjects. All patients underwent cardiovascular tests (Valsalva maneuver, deep breathing test, response to standing, blood pressure response to standing sustained, handgrip test), electrocardiogram, treadmill exercise test and filled out a questionnaire referring to major cardiovascular risk factors: smoking, obesity, hypertension, and dyslipidemia. Results. Our results showed that cardiovascular autonomic neuropathy was more frequent in type 2 diabetes, manifesting as autonomic neuropathy. In patients with autonomic neuropathy, regardless of the type of diabetes, the treadmill test was positive, i.e. strongly correlating with coronary disease. In regard to coronary disease risk factors, the most frequent correlation was found for obesity and hypertension. Discussion Cardiovascular autonomic neuropathy is considered to be the principal cause of arteriosclerosis and coronary disease. Our results showed that the occurrence of cardiovascular autonomic neuropathy increases the risk of coronary disease due to dysfunction of autonomic nervous system. Conclusions. Cardiovascular autonomic neuropathy is a common complication of diabetes that significantly correlates with coronary disease. Early diagnosis of cardiovascular autonomic neuropathy points to increased cardiovascular risk, providing a basis for preventive and therapeutic measures. .

Shifting healthcare monitoring techniques from laboratory into real-life scenarios has always been very challenging. The current shift towards the use of advanced sensors into everyday objects (e.g., smartwatches) is actively increasing the need for reliable methods and tools to analyse healthcare information acquired in real-life settings for wellbeing applications. In fact, the diffusion of wearable sensors has opened new and unexplored scenarios for Cardiovascular System (CVS) and Autonomic Nervous System (ANS) monitoring in real-life settings. As such, this thesis aims to develop methods and tools to monitor the relationship between CVS and ANS in real-life settings via biomedical signal processing and data-driven machine learning techniques, with the goal of predicting adverse healthcare events and automatically detecting the onset of unhealthy risky situations. Therefore, to investigate the relation between CVS and ANS, electrocardiogram signals and in particular Heart Rate Variability (HRV) were widely investigated in two case studies: acute mental stress detection and prediction of accidental falls in later-life via HRV. One of the main limitations of using wearable sensors for the detection of risky situations in real-life settings is the need to shorten the length of physiological signals below the standard recommendations, which may cause a loss of accuracy in the detection of adverse healthcare events. Therefore, this problem was investigated taking as an exemplar mental stress detection, which is a cogent problem for modern society and it is well-known that mental stress causes alterations in both CVS and ANS. Through a systematic review of the literature, it was demonstrated that little attention has been paid thus far to ultra-short term HRV analysis (i.e., less than 5 minutes) for mental stress detection. Consequently, four experiments were designed and carried out in real-life and in-lab environments to propose a systematic method combining both statistical and machine learning methods to select ultrashort HRV features that are reliable surrogates of 5min HRV features. As a consequence, this study proved that it is possible to automatically detect real mental stress with 1min recordings achieving accuracy rate of 88%. Another limitation of using wearable sensors is the need to improve machine learning techniques to enhance the prediction of rare events. In order to address this, an unbalanced dataset was investigated. In particular, a study was designed to apply data-driven machine learning techniques to an unbalanced dataset of ECG recordings acquired from 170 hypertensive elderly patients, of which 34 experienced an accidental fall. An experimental framework for data-driven machine learning techniques to detect rare events (i.e., falls) was developed to reduce the risk of overfitting problems in unbalanced datasets. This study was the first proving that short term HRV recordings could be used to identify future fallers with high accuracy. This research achieved novel results and significant knowledge advancement for both the investigated well-being and health problems as well as methodological techniques.

Multiple System Atrophy (MSA) and Pure Autonomic Failure (PAF) are contrasting models of Chronic Autonomic failure. PAF primarily involves the post-ganglionic autonomic nervous system, whilst in MSA the pre-ganglionic structures are impaired. My central hypothesis is that this underlying neuropathological difference between MSA and PAF will lead to differing cardiovascular responses. I will assess the cardiovascular effects of known pressor and vasomotor stimuli (mental arithmetic, cold pressor test, isometric exercise, water ingestion, inhaled CO₂ and inspiratory gasp) in MSA and PAF. Neurohormonal aspects will be explored by comparing the cardiovascular effects of the α2-adrenoceptor agonist clonidine with serum noradrenaline levels in these groups, as well as comparing supine antidiuretic hormone (ADH) levels after head up tilt and correlating these with supine blood pressure (BP). As well as contrasting the cardiovascular responses, I will use the water ingestion studies to examine effects on orthostatic hypotension, a common complication of both MSA and PAF. To measure cardiovascular responses during these studies I have used the Portapres II device to obtain continuous, non-invasive, beat-to-beat measurements of BP and heart rate (HR). Subsequent Model flow analysis using Beatscope software has then been used to calculate further cardiovascular indices, including cardiac output (CO), stroke volume (SV) and total peripheral resistance (TPR). In addition, intermittent BP and HR measurements have been obtained with an automated sphygmomanometer (Dinamap). Finally, peripheral vasomotor responses have been recorded by means of the Laser Doppler perfusion meter.

There is clear evidence that the autonomic nervous system (ANS) is lateralized at both the peripheral as well as the central levels of the nervous system. Both the vagus and the sympathetic ganglia asymmetrically innervate the sino-atrial node and the myocardium of the heart. This lateralization has also been observed in afferent as well as efferent projections to nuclei in the brainstem, hypothalamus, and amygdala. Where laterality has not been as clear is in regions of the frontal lobe dedicated to the regulation of autonomic nervous system responses. This study addressed that issue via the implementation of lateralized autonomic response-evoking tasks. With the use of cardiovascular and electrodermal measures, the present study indexed autonomic responses to lateralized stimuli. This study also explored the role of lateralization within sex as well as in relation to reported gender identity. The findings lend support to the right hemisphere as serving a dominant role in regulating sympathetic nervous system activity, while lending less conclusive support for lateralization of parasympathetic nervous system regulation. Men demonstrated greater lateralization for sympathetic nervous system responses across several different metrics of autonomic indices. The exploration of gender variables in relation to lateralization of autonomic responses was generally not supported.
Master of Science

Brugada syndrome (BS) is a genetic arrhythmogenic disease characterized by a distinctive electrocardiographic pattern, associated with a high risk for sudden cardiac death (SCD) due to ventricular fibrillation (VF) in absence of structural cardiopathies. Its complex and multifactorial nature turns risk stratification into a major challenge. Although variations in autonomic modulation are commonly related to arrhythmic events in this population, novel markers with higher predictive values are still needed so as to identify those patients at high risk. The autonomic function can be better characterized through the application of standardized maneuvers stimulating the autonomic nervous system (ANS), such as exercise testing or the head-up tilt (HUT) test. Therefore, in this PhD thesis a thorough evaluation of the cardiovascular response to ANS modulations overnight is proposed, as well as in response to exercise and HUT testing, on a clinical database composed of BS patients with different levels of risk (symptomatic and asymptomatic subjects). In this context, the autonomic function was assessed by three main approaches. First, through the characterization and comparison of previously described methods capturing heart rate complexity, baroreflex sensitivity, and non-stationary heart rate variability, never before studied in the context of BS patients; in order to identify new markers capable of distinguishing between symptomatic and asymptomatic patients. According to the results, a lower variability and complexity overnight, as well as a higher vagal tone and a lower sympathetic activity both during exercise and HUT testing, was observed in the symptomatic group. In a second analysis, in order to address the multifactorial nature of the disease, a multivariate approach based on a step-based machine learning method was introduced. By employing features extracted at signal-processing analysis, robust classifiers capable of identifying patients at high risk were proposed. The classifier based on autonomic features extracted during nighttime analysis presented the best performance (AUC=95%), improving previously reported predictive models of risk in BS based on non-invasive parameters. Finally, the third part of this work was focused on the implementation of novel mathematical models and the associated model analysis methods, so as to study the autonomic mechanisms regulating the mechanical and circulatory functions of the cardiovascular system in this population. First, by the integration and evaluation of a computational model capturing the cardiovascular system's dynamics and its autonomic regulation in response to HUT testing. Likewise, a second model-based approach based on a recursive identification of the sympathetic and parasympathetic contributions to ANS regulation was proposed in order to estimate the time-varying autonomic response to exertion and subsequent recovery. The results showed a reduced contractility function, as well as a significantly greater parasympathetic activity during exercise, in symptomatic patients. Finally, in order to combine characteristics extracted from model-based approaches, a prospective study introduced a multivariate classifier based on estimated model parameters. Overall, the obtained results indicate important trends of clinical relevance that provide new insights into the underlying autonomic mechanisms regulating the cardiovascular system in BS, improving physiopathology and prognosis interpretation, with a potential future impact on therapeutic strategies. The proposed approach is presented as a potential instrument for the identification of those asymptomatic patients at high risk who may benefit from a cardioverter defibrillator implantation.
El síndrome de Brugada (SB) es una enfermedad genética asociada a un patrón electrocardiográfico característico y a un elevado riesgo de muerte súbita cardíaca (MSC), causada por fibrilación ventricular (FV) en ausencia de cardiopatías estructurales. Debido a su naturaleza compleja y multifactorial, la estratificación del riesgo supone, en la actualidad, uno de los aspectos más controvertidos. Ciertas alteraciones en la modulación del sistema nervioso autónomo (SNA) se han relacionado con eventos arrítmicos en esta población; no obstante, nuevos marcadores con valores predictivos más elevados que permitan identificar a aquellos pacientes con un alto riesgo de sufrir MSC son todavía necesarios. El uso de maniobras estandarizadas con el objetivo de estimular el SNA permiten mejorar la caracterización de la función autonómica. Por ello, en esta tesis doctoral se propone una evaluación exhaustiva de la respuesta cardiovascular a la modulación del SNA durante la noche, así como en respuesta al ejercicio y a la prueba de mesa inclinada, en una base de datos clínicos compuesta por sujetos con diferentes niveles de riesgo (pacientes sintomáticos y asintomáticos). En este contexto, la evaluación de la función autonómica se llevó a cabo mediante tres estrategias principales. En primer lugar, se caracterizaron y compararon la variabilidad y complejidad del ritmo cardíaco, así como la sensibilidad barorrefleja, en pacientes sintomáticos y asintomáticos, con el objetivo de identificar nuevos marcadores capaces de distinguir entre grupos de pacientes. Los resultados mostraron, en el grupo sintomático, una menor variabilidad y complejidad durante la noche, así como un mayor tono vagal y una menor actividad simpática tanto durante el ejercicio como en respuesta a la prueba de mesa inclinada. En un segundo análisis, se abordó la etiología multifactorial del síndrome mediante un enfoque multivariado basado en un método de aprendizaje automático por etapas. A partir de marcadores extraídos en la etapa anterior, se propusieron modelos predictivos capaces de clasificar pacientes diagnosticados con SB en función de su nivel de riesgo. El mejor clasificador (AUC = 95%) fue diseñado a partir de marcadores autonómicos obtenidos durante la noche, superando modelos predictivos previamente descritos para la estratificación del riesgo en el SB a partir de la combinación de parámetros no invasivos. Finalmente, se analizaron las interacciones entre las funciones mecánica, circulatoria y autonómica de estos pacientes a partir de modelos fisiológicos. En primer lugar, mediante la implementación y evaluación de un modelo computacional integrando la dinámica del sistema cardiovascular y su respuesta autonómica a la prueba de mesa inclinada. Asimismo, se propuso la identificación recursiva de un modelo implementado para el análisis de la evolución temporal de las contribuciones simpática y parasimpática del SNA durante una prueba de esfuerzo. Los resultados mostraron una menor contractilidad, así como una actividad parasimpática significativamente mayor durante el ejercicio, en pacientes sintomáticos. Con el objetivo de combinar características extraídas del modelado fisiológico, un último estudio prospectivo propuso el diseño de un clasificador multivariado integrando los parámetros estimados en esta última etapa. Los resultados obtenidos indican importantes tendencias de relevancia clínica que aportan nuevos conocimientos sobre los mecanismos autonómicos encargados de regular el sistema cardiovascular en el SB. Su interpretación permite mejorar la estratificación del riesgo en estos pacientes y, por tanto, optimizar las estrategias terapéuticas aplicadas. La metodología propuesta se presenta como un instrumento para la identificación de aquellos pacientes con alto riesgo de MSC que podrían beneficiarse de la implantación de desfibriladores automáticos.
Le syndrome de Brugada (BS) est une maladie cardiaque caractérisée par la survenue d’une syncope ou mort subite, provoquées par une arythmie cardiaque, chez les patients avec un coeur structurellement normal, mais présentant des altérations électrocardiographiques spécifiques. Cependant, ces modifications sont intermittentes et varient avec la température ou les traitements appliqués, ce qui rend particulièrement difficile le diagnostic chez un patient donné. En outre, elles sont fortement modulées par le système nerveux autonome (SNA), partie du système nerveux périphérique responsable de la régulation des organes internes. Les défibrillateurs implantables (DI) sont le traitement principal pour les patients symptomatiques, c’est-à-dire les patients documentés d’arythmie ventriculaire, syncope ou ayant survécu à un épisode de mort subite. Cependant, la décision d’implanter un DI peut être très difficile pour des patients asymptomatiques sans antécédents familiaux de morte subite. Dans ce contexte, l’objectif de la thèse était d’améliorer la compréhension de l’influence du SNA chez les patients souffrant du BS. Une méthodologie globale fusionnant traitement du signal, machine learning et modélisation a été proposée durant la thèse. Cette chaine de traitement originale a pu être mise en oeuvre sur trois bases de données de patients BS symptomatiques et asymptomatiques. Les bases de données cliniques utilisées dans ce travail sont le résultat d’une étude prospective, multicentrique dont l’objectif était de provoquer des modifications de l’activité du SNA chez les patients BS. L’acquisition des données s’est déroulée entre 2009 et 2013 dans le service de cardiologie du CHU de Rennes et les participants provenaient de 8 hôpitaux français situés à La Rochelle, Angers, Bordeaux, Brest, Nantes, Rennes, Poitiers et Tours. Afin de caractériser les patients présentant différents niveaux de risque, les participants ont été classés en patients symptomatiques et asymptomatiques, selon leurs historiques cliniques. Les patients symptomatiques devaient présenter les symptômes documentés suivants : arrêt cardiaque dû à une fibrillation ventriculaire, syncopes, vertiges, palpitations et convulsions nocturnes. La base de données est constituée des ECG (12 dérivations) de 87 patients, collectés pendant 24 heures, incluant un test d’orthostatisme (tilt-test) et une épreuve d’effort. L’acquisition était réalisée à l’aide d’un moniteur Holter (ELA medical, Sorin Group, Le Plessis Robinsson, France) à une fréquence d’échantillonnage de 1000 Hz. Par ailleurs, des tilt-tests ont été réalisés sur 32 patients en mesurant de manière non-invasive la pression artérielle et l’ECG avec le moniteur Task Force (CN Systems, Graz, Autriche) à une fréquence d’échantillonnage de 100 Hz et 1000 Hz, respectivement. Des signaux ECG à 12 dérivations échantillonnés à 1000 Hz ont été acquis chez 36 autres patients BS lors d’un test d’exercice avec le moniteur ECG (Cardionics, Webster, Texas). Par conséquent, l’analyse de l’activité du système nerveux autonome est basée sur 3 périodes différentes : 1) une épreuve d’effort, 2) un test d’orthostatisme (tilt-test) et 3) un recueil de données pendant la nuit. La réponse du système nerveux autonome, à ces trois tests, a tout d’abord été évaluée avec des méthodes d’estimation du gain du baroréflexe, de variabilité et de complexité cardiaque. L’une des difficultés du traitement des signaux associés à l’épreuve d’effort et au test d’orthostatisme réside dans leurs natures non-stationnaires. L’analyse spectrale de ces signaux nécessite la mise en oeuvre d’outils spécifiques permettant de décrire une évolution temporelle des caractéristiques fréquentielles. Des analyses temps-fréquence, basées sur la transformée de Wigner-Ville, ont ainsi été utilisées afin d’étudier conjointement, le contenu spectral des signaux, et leurs évolutions temporelles. Cependant, ces méthodes classiques d’analyse de la variabilité cardiaque ne permettent pas de capturer la non-linéarité de la dynamique cardiovasculaire. Ainsi, des méthodes spécifiques d’analyse de la complexité des séries cardiaques ont pu être utilisées. La sensibilité du baroréflexe de ces patients a été évaluée à partir de différentes méthodes proposées dans la littérature. Une série d’indices a ainsi été déduite des signaux avant d’être analysée pour trouver des différences significatives entre les patients symptomatiques et asymptomatiques. Les résultats ont mis en évidence que les indices calculés chez les patients symptomatiques sont associés à une baisse de la variabilité et de la complexité cardiaque pendant la nuit. Par ailleurs, pendant le test d’exercice, les patients symptomatiques ont montré une activité vagale augmentée et un tonus sympathique réduit. Lors de la réponse au tilt-test, les patients symptomatiques ont présenté une augmentation du tonus parasympathique et une réduction de l’équilibre sympatho-vagal par rapport aux patients asymptomatiques. L’étiologie multifactorielle du BS nécessite l’utilisation d’approches complexes capables de capturer les multiples mécanismes sous-jacents à la maladie. Ainsi, une analyse multivariée a été réalisée à partir de la série d’indices calculés précédemment. L’approche globale, basée sur des méthodes de machine learning, permet de combiner de manière optimale les indices autonomiques extraits précédemment, afin de concevoir des classificateurs capables de différencier les patients BS, en fonction de leur symptomatologie. La sélection de ces indicateurs autonomiques, permettant une meilleure caractérisation du BS, peut être difficile surtout lorsque le nombre de sources dépasse la quantité d’observations et que les variabilités entre patients sont significatives. Ainsi, une approche robuste basée sur un processus de sélection de paramètres en deux étapes a été mise en oeuvre. La méthodologie proposée a été optimisée, évaluée et comparée sur les données extraites lors de différents tests autonomiques. Les résultats montrent que le meilleur classificateur (AUC = 95%) a été conçu à partir de marqueurs autonomiques obtenus pendant la nuit, améliorant des modèles prédictifs décrits précédemment pour la stratification du risque dans le BS à partir de la combinaison de paramètres non invasifs. Bien que l’analyse multivariée proposée montre une amélioration des performances de classification par rapport à la littérature, les méthodes utilisées n’intègrent pas de connaissance physiologique dans le traitement des données. Or le BS étant une pathologie complexe et multifactorielle, l’utilisation de modèles mathématiques de connaissance peut s’avérer pertinente car cela permet l’intégration d’information physiologique dans le traitement des données et l’analyse de mécanismes sous-jacents qui sont difficiles ou impossibles à observer en clinique avec des méthodes non-invasives, comme le tonus vagal ou sympathique. Une analyse à base de modèle a été proposée durant la thèse afin : 1) d’étudier la réponse autonomique et hémodynamique au test d’orthostatisme chez des sujets sains et des patients BS, 2) de simuler les réponses vagales et sympathiques durant l’épreuve d’effort chez les patients BS symptomatiques et asymptomatiques. Concernant l’étude de la réponse au test d’orthostatisme, un modèle a été proposé de manière à intégrer les représentations : i) de l’activité électrique cardiaque, ii) de la mécanique des ventricules et des oreillettes, iii) des circulations systémique et pulmonaire et iv) du baroréflexe incluant les voies vagale et sympathique. Le modèle complet permet de simuler les réponses hémodynamiques et autonomiques au test d’orthostatisme. Des analyses de sensibilité, basées sur des méthodes globales et de criblage, ont mis en évidence l’importance de certains paramètres du baroréflexe et en lien avec la description des propriétés diastoliques des ventricules. Ces paramètres ont pu être identifiés, à l’aide d’algorithmes évolutionnaires, afin de créer des modèles spécifiques-patients de 8 sujets sains et 12 patients BS. Les résultats ont montré des différences significatives concernant la réponse sympathique au tilt-test entre sujets sains et BS. Par ailleurs, les patients symptomatiques et asymptomatiques sont associés des modifications significatives des paramètres diastoliques ventriculaires. Concernant les simulations de la réponse autonomique durant l’épreuve d’effort, un algorithme d’identification récursif a pu être mis en oeuvre sur un modèle composé des cavités cardiaques, des circulations systémique et pulmonaire, couplées au baroréflexe. L’identification récursive réalisée sur le modèle a permis une estimation des activités vagale et sympathique durant l’effort chez 13 patients BS symptomatiques et 31 asymptomatiques. Les patients symptomatiques ont montré une élévation significative de l’activité vagale, spécialement à la fin de l’échauffement. Les analyses réalisées sur les modèles proposés, concernant le test d’orthostatisme et l’épreuve d’effort, ont permis une exploration de variables physiologiques, difficilement observables. Les résultats obtenus avec les modèles mettent en évidence des modifications de la réponse hémodynamique cardiaque et confirment des modifications de la balance sympatho-vagale entre les patients symptomatiques et asymptomatiques. En résumé, les résultats obtenus mettent en évidence un déséquilibre de la balance sympathovagale entre les patients symptomatiques et asymptomatiques et montrent l’utilité des indices de variabilité cardiaque pour la classification des patients en fonction de la symptomatologie. Les résultats obtenus sont cohérents avec la littérature, rapportant un tonus vagal plus élevé, ainsi qu’une activité sympathique, variabilité et complexité cardiaques plus faibles, chez les patients symptomatiques. Des études précédentes ont rapporté que la plupart des événements cardiaques majeurs se produisent au repos et pendant le sommeil, ainsi que l’apparition des altérations électrocardiographiques caractéristiques du BS augmente avec la stimulation vagale. Les résultats obtenus pendant la nuit, lorsque l’activité parasympathique est prédominante, ont montré des résultats particulièrement pertinents pour la différentiation des populations de patients. De plus, étant donnée qu’il existe une activité parasympathique significativement plus élevée chez les patients symptomatiques pendant les tests d’exercice et d’orthostatisme par rapport aux sujets asymptomatiques, les résultats soulignent le rôle de l’analyse du tonus vagal pour la stratification du risque dans cette population. Enfin, l’analyse basée sur un modèle du système cardiovasculaire a permis de mettre en évidence des différences concernant les propriétés diastoliques cardiaques et la réponse du baroréflexe pendant le test d’orthostatisme. L’ensemble des résultats de la thèse permet une meilleure caractérisation des profils autonomiques des patients atteints du syndrome de Brugada et laisse envisager une amélioration de la sélection des patients pour implantation d’un DI.

Le syndrome de Brugada (BS) est une maladie génétique responsable de troubles du rythme cardiaque. En raison de la nature complexe et multifactorielle de cette pathologie, la stratification du risque peut s’avérer particulièrement difficile et il est nécessaire de pouvoir définir de nouveaux marqueurs avec des valeurs prédictives élevées afin d’identifier les patients à haut risque. Les événements arythmiques dans cette population étant souvent liés à des modifications de fonctionnement du système nerveux autonome (SNA), l’objectif de la thèse est l’évaluation et comparaison de la réponse cardiovasculaire aux modulations du SNA pendant la nuit, ainsi qu'en réponse à des manœuvres normalisées, telles que l'épreuve d'effort ou le test d'orthostatisme, chez une série de patients BS présentant différents niveaux de risque (sujets symptomatiques et asymptomatiques). Une première partie du travail de thèse est dédiée à l’application de méthodes d'analyse de complexité cardiaque, de sensibilité baroréflexe et de variabilité non-stationnaire du rythme cardiaque, jamais étudiées dans le cadre des patients BS. Dans une deuxième partie, afin d'aborder la nature multifactorielle de la maladie, une approche multivariée basée sur une méthode de machine learning est introduite. En employant des marqueurs extraits à l'analyse du traitement du signal précédent, des classificateurs robustes capables de distinguer les patients à différents niveaux de risque sont proposés. Dans la troisième partie de ce travail, deux modèles mathématiques de connaissances ont été proposés et analysés, afin d'étudier les réponses autonomiques et hémodynamiques au test d’orthostatisme et à l’épreuve d’effort. Enfin, une application prospective d’une approche multivariée intégrant les paramètres extraits à l'étape de modélisation est également présentée. L’ensemble des résultats de la thèse permet une meilleure caractérisation des profils autonomiques des patients BS et laisse envisager une amélioration de la sélection des patients pour implantation d'un défibrillateur implantable
Brugada syndrome (BS) is a genetic arrhythmogenic disease characterized by a distinctive electrocardiographic pattern, associated with a high risk for sudden cardiac death. Its complex and multifactorial nature turns risk stratification into a major challenge. Although variations in autonomic modulation are commonly related to arrhythmic events in this population, novel markers with higher predictive values are still needed so as to identify those patients at high risk. Since the autonomic function can be better characterized through the application of standardized maneuvers stimulating the autonomic nervous system (ANS), the main objective of this thesis is to evaluate and compare the cardiovascular response to ANS modulations overnight, as well as in response to exercise and HUT testing, on a series of BS patients with different levels of risk (symptomatic and asymptomatic subjects). In a first part of this work, we apply previously described methods for the analysis of heart rate complexity, baroreflex sensitivity, and non-stationary heart rate variability, never before studied in the context of BS patients. In a second part, in order to address the multifactorial nature of the disease, a multivariate approach based on a step-based machine learning method is introduced. By employing markers extracted at signal-processing analysis, robust classifiers capable of distinguishing patients at different levels of risk are proposed. The third part of this work has been focused on the proposal of novel mathematical models and the associated model analysis methods, so as to study the autonomic and hemodynamic responses to exercise and HUT testing. Finally, a prospective application of a multivariate approach integrating parameters extracted at the model-based stage is also presented. Overall, the obtained results provide new insights into the underlying autonomic mechanisms regulating the cardiovascular system in BS, improving physiopathology and prognosis interpretation. The proposed approach may be used as an instrument for the identification of those asymptomatic patients at high risk who may benefit from a cardioverter defibrillator implantation
El síndrome de Brugada (SB) es una enfermedad genética asociada a un patrón electrocardiográfico característico y a un elevado riesgo de muerte súbita cardíaca (MSC), causada por fibrilación ventricular (FV) en ausencia de cardiopatías estructurales. Debido a su naturaleza compleja y multifactorial, la estratificación del riesgo supone, en la actualidad, uno de los aspectos más controvertidos. Ciertas alteraciones en la modulación del sistema nervioso autónomo (SNA) se han relacionado con eventos arrítmicos en esta población; no obstante, nuevos marcadores con valores predictivos más elevados que permitan identificar a aquellos pacientes con un alto riesgo de sufrir MSC son todavía necesarios. El uso de maniobras estandarizadas con el objetivo de estimular el SNA permite una mejor caracterización de la función autonómica. El principal objetivo de esta tesis doctoral es, por tanto, la evaluación exhaustiva de la respuesta cardiovascular a la modulación del SNA en una serie de pacientes con SB y diferentes niveles de riesgo (sujetos sintomáticos y asintomáticos), a través de diferentes maniobras autonómicas, con la finalidad de identificar nuevos marcadores potencialmente útiles para la estratificación de riesgo en esta población. En este contexto, la evaluación de la función autonómica se llevó a cabo mediante tres estrategias principales. En primer lugar, se caracterizaron y compararon la variabilidad y complejidad del ritmo cardíaco, así como la sensibilidad barorrefleja, en pacientes sintomáticos y asintomáticos, con el objetivo de identificar nuevos marcadores capaces de distinguir entre grupos de pacientes. Los resultados mostraron, en el grupo sintomático, una menor variabilidad y complejidad durante la noche, así como un mayor tono vagal y una menor actividad simpática tanto durante el ejercicio como en respuesta a la prueba de mesa inclinada. En un segundo análisis, se abordó la etiología multifactorial del síndrome mediante un enfoque multivariado basado en un método de aprendizaje automático por etapas. A partir de marcadores extraídos en la etapa anterior, se propusieron modelos predictivos capaces de clasificar pacientes diagnosticados con SB en función de su nivel de riesgo. El mejor clasificador (AUC = 95%) fue diseñado a partir de marcadores autonómicos obtenidos durante la noche, superando modelos predictivos previamente descritos para la estratificación del riesgo en el SB a partir de la combinación de parámetros no invasivos. Finalmente, se analizaron las interacciones entre las funciones mecánica, circulatoria y autonómica de estos pacientes a partir de modelos fisiológicos. En primer lugar, mediante la implementación y evaluación de un modelo computacional integrando la dinámica del sistema cardiovascular y su respuesta autonómica a la prueba de mesa inclinada. Asimismo, se propuso la identificación recursiva de un modelo implementado para el análisis de la evolución temporal de las contribuciones simpática y parasimpática del SNA durante una prueba de esfuerzo. Los resultados mostraron una menor contractilidad, así como una actividad parasimpática significativamente mayor durante el ejercicio, en pacientes sintomáticos. Con el objetivo de combinar características extraídas del modelado fisiológico, un último estudio prospectivo propuso el diseño de un clasificador multivariado integrando los parámetros estimados en esta última etapa. Los resultados obtenidos indican importantes tendencias de relevancia clínica que aportan nuevos conocimientos sobre los mecanismos autonómicos encargados de regular el sistema cardiovascular en el SB. Su interpretación permite mejorar la estratificación del riesgo en estos pacientes y, por tanto, optimizar las estrategias terapéuticas aplicadas. La metodología propuesta se presenta como un instrumento para la identificación de aquellos pacientes con alto riesgo de MSC que podrían beneficiarse de la implantación de desfibriladores automáticos

Abstract Regular aerobic training has been suggested to protect the heart by increasing cardiac vagal activity. The aims of this study were to evaluate the autonomic regulation of heart rate (HR) during and after exercise, during aerobic training interventions and to study the association between autonomic regulation and the training response in healthy male subjects. HR variability assessment was used to study the effects of exercise on autonomic regulation of HR. The whole study population consisted of 70 volunteer male subjects (age 36 ± 10 years). The recovery of the autonomic nervous system after prolonged exhaustive exercise was studied in a group of 10 subjects. The training interventions included 51 subjects. The effects of training volume on autonomic regulation were assessed (n = 46) during a controlled eight-week training intervention. The association between training and autonomic regulation was studied (n = 24) during a ten-month period of home-based training based on the American College of Sports Medicine recommendations. Finally, the association between autonomic regulation and the individual training response was analysed (n = 51) after eight weeks of controlled training. The recovery rate of vagally mediated high-frequency (HF) power of HR variability after prolonged exhaustive exercise was associated with physical fitness (r = -0.71, P < 0.016). Moderate (3 hours/week) and high-volume (6 hours/week) aerobic training results in a similar increase in HR variability indices. HF power increased from 6.19 ± 1.02 to 6.76 ± 0.96 ln ms2 (P < 0.001) and from 6.61 ± 1.01 to 7.12 ± 0.92 ln ms2 (P < 0.001) after moderate and high-volume training, respectively. During the home-based training program, the changes in HF power were associated with the changes in the fitness (r = 0.44, P < 0.05), body mass index (r = -0.44, P < 0.05) and the amount of training (r = 0.41, p < 0.05). Finally, a significant correlation was observed between the training response and the baseline HF power (r = 0.52, P = 0.001). HF power accounted for 27 % of the change as an independent predictor of the aerobic training response. In conclusion, a highly controlled aerobic training intervention of eight weeks, including six 30-min sessions a week at an intensity of 70–80 % of maximum HR, is a sufficient intervention to increase cardiac vagal outflow and the offered home-based training according the current guidelines maintains the high cardiac vagal outflow. Secondly, high vagal activity at baseline is associated with the improvement in aerobic fitness caused by aerobic training, suggesting that the cardiovascular autonomic function is an important determinant of the response to aerobic training.

Purpose: To determine the cardiovascular, respiratory, systemic inflammatory, and autonomic nervous system responses to varying exercise intensities during exposure to diesel exhaust (DE), and to determine how DE exposure before exercise affects the cardio-respiratory system and subsequent exercise performance. Methods: Eighteen males performed six 30-minute trials, which included rest, low-intensity, and high-intensity cycling. Each trial was performed twice, once breathing filtered air (FA) and once breathing DE (300ug/m³ of PM₂.₅) with seven days between trials. Before, and following exercise, exhaled nitric oxide, pulmonary function, heart rate variability, flow-mediated dilation (FMD), complete blood count, endothelin-¹ , and plasma nitrite/nitrate (NOx) were measured. During exercise, minute ventilation (VE), oxygen consumption (VO₂), CO₂ production (VCO₂), respiratory exchange ratio (RER), and rating of perceived exertion (RPE) for lungs and legs were measured. In a second experiment, eight males were exposed to DE (300ug/m³ of PM₂.₅) or FA for 60-minutes, followed by an indoor 20-km cycling time trial. Pulmonary function was assessed before and after exposure and after exercise. Heart rate was measured during exposure and exercise performance was measured as mean power output during exercise. Results: In the first experiment, RER was significantly lower (0.94 vs. 0.96), and RPE significantly greater, in DE compared to FA (p<0.05). During low-intensity exercise, VE (44.5 vs. 40.5 L•min-¹ ), VO₂ (27.9 vs. 24.9 ml*kg*min-¹) and VCO₂ (25.9 vs. 23.6 ml*kg*min-¹) were significantly greater during DE (p<0.05). Following exercise in DE, plasma NOx significantly increased (p<0.05). On low-intensity exercise days, FMD/shear rate area under the curve (SRAUC) was significantly lower in DE compared to FA (9.7 x 10-⁵ vs. 11.7x10-⁵; p<0.05). In the second experiment, we found that pre-exercise exposure to DE did not impair exercise performance but attenuated exercise-induced bronchodilation and increased exercise heart rate (163.9 vs. 157.3bpm; p<0.05). Conclusion: Metabolic and endothelial responses to low- but not high-intensity cycling in DE differ from those in FA. Therefore, reducing exercise intensity during bouts of air pollution may have no benefit. Exposure to DE prior to exercise increased exercise heart rate and decreased exercise-induced bronchodilation. Consequently, encouraging individuals to minimize exposure to air pollution prior to exercise could be beneficial.

Motivation Hypertension is a pertinent health problem for urban black African men (hereafter referred to as African). Sympathetic hyperactivity and a dominant α-adrenergic response pattern have both been implicated as contributing factors to their poor cardiovascular health. In addition to the deleterious effect of neurogenic hypertension on target organs, sympathetic hyperactivity may promote the accelerated progression of left ventricular hypertrophy and structural vascular disease. Aim The overarching aim of this study is to scrutinize autonomic control of the cardiovascular system in a cohort of urban African and Caucasian men during a mental challenge. Associations were investigated between potential sympatho-vagal imbalance, blood pressure and target organ damage markers to determine cardiovascular risk in ethnic male groups. Methodology The SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) study involved the participation of 200 male teachers (99 African and 101 Caucasian) in the Kenneth Kaunda Education District of the North-West Province, South Africa. Of the participant group, HIV-infected (13 African) and clinically confirmed diabetics (1 Caucasian and 6 African men) were excluded from further analyses. Stratification was based on ethnicity and further as indicated through statistical interaction effects. Cardiovascular and autonomic responses were assessed during rest and on stressor exposure (cold pressor test and Stroop colour-word conflict test). Autonomic measures included baroreceptor sensitivity (BRS), 3-methoxy-4-hydroxy-phenylglycol (MHPG) and nitric oxide metabolite (NOx) levels. Cardiovascular variables consisted of blood pressure, cardiac output, stroke volume, total peripheral resistance, heart rate, arterial compliance and ST-segment from the 12-lead electrocardiogram. Markers of target organ damage included the Cornell product (indication of left ventricular hypertrophy) and carotid intima-media thickness as indication of structural vascular disease. Means and proportions were compared by means of standard t-test and Chi-square test, respectively. Significant differences of mean cardiovascular and autonomic measures between ethnic male groups were also determined through analysis of covariance. Uni- and multivariate regression analyses were employed to demonstrate associations between target organ damage, cardiovascular and autonomic markers. Results and conclusion of each manuscript To assess autonomic nervous system and cardiovascular function as well as target organ damage, we clearly focussed on responses where our participants were challenged. Markers of autonomic responses assessed were baroreceptor sensitivity, 3-methoxy-4-hydroxyphenylglycol and nitric oxide metabolites.  The first manuscript (Chapter 2) focused on left ventricular hypertrophy as marker of target organ damage, blood pressure and baroreceptor sensitivity as marker of autonomic function. The objective was to determine whether BRS was significantly lower in African men than in the Caucasian men. Furthermore, the possible association between attenuation of BRS and increased levels of ambulatory blood pressure as well as left ventricular hypertrophy was investigated in these population groups. Results revealed that the African men had significantly lower BRS stress responses. This attenuated BRS profile was coupled with dominant α-adrenergic response patterns, which was associated with an elevation of ambulatory blood pressure. BRS attenuation (rest and stress response) was not associated with left ventricular hypertrophy. It was concluded that lower BRS, especially during stress, may pose a significant health threat for urban African men regarding the development or promotion of α-adrenergic-driven hypertension and higher cardiovascular disease risk.  The aim of the second sub-study (Chapter 3) was to investigate possible associations between structural vascular disease (carotid intima-media thickness as marker), autonomic function (MHPG as marker) and nocturnal blood pressure in the African and Caucasian men. Results showed a higher prevalence of nocturnal hypertension in the African men, with night-time blood pressure significantly higher compared to the Caucasian men. In the African and Caucasian men, carotid intima-media thickness was linearly predicted by nocturnal systolic and diastolic blood pressure respectively. In conclusion, no associations were demonstrated between MHPG and carotid intimamedia thickness or between MHPG and nocturnal blood pressure. Elevated nocturnal blood pressure evidently seems to promote structural vascular disease in this cohort of urban African and Caucasian men.  The aim of the third manuscript presented in Chapter 4, was to investigate bioavailability of NO during mental challenge (autonomic function marker) and the possible association with structural vascular disease (carotid intima-media thickness as marker). In the African men, an attenuated NOx response was demonstrated to the Stroop colour-word conflict test. After stratification into high and low NOx response groups, in the African men with a low NOx response enhanced α-adrenergic with significant STsegment depression responses was demonstrated indicating reduced myocardial oxygen supply during mental stressor exposure. Only in the African men, a ST-segment depression was significantly associated with structural vascular disease. It was concluded that the African men demonstrated a vulnerable cardiovascular profile. In this cohort of African men, the significant association between structural vascular disease and myocardial ischemia may particularly indicate a possible higher risk for future cardiovascular events. General conclusion Through the assessment of autonomic and cardiovascular responses a possible higher cardiovascular risk was demonstrated in the African men. In this cohort sympathetic hyperactivity was evident, coupled with dominant vascular response patterns and reduced myocardial oxygen supply during mental stress exposure. Based on these findings, this population group’s risk for accelerated target organ damage, as well as for future cardiovascular events, appear significantly higher than those of the Caucasian male cohort.
Thesis (PhD (Physiology))--North-West University, Potchefstroom Campus, 2013.

Three studies were designed to investigate the effects of exercise-based lifestyle interventions including diet change and exercise training on cardiovascular and autonomic responses to various physical and mental challenges in untrained premenopausal women. In Study 1, the effects of different tasks designed to activate the sympathetic nervous system on autonomic control of cardiovascular functioning such as the Stroop colour-word task (Stroop) and lower body negative pressure (LBNP) in 20 untrained premenopausal women (22.6??0.7 years) were determined. In Study 2, a longitudinal exercise intervention strategy was used with 18 untrained premenopausal women (22.5??0.7 years) in order to investigate the effect of 15 weeks of high intensity intermittent exercise (HIIE) training on cardiac autonomic responses to mental challenge (Stroop) and LBNP. In Study 3, the effects of HIIE training combined with a Mediterranean-style eating plan and fish oil supplement (Fish oil, Exercise, Mediterranean diet; FEM) on cardiovascular function during mental challenge (Stroop) and physical tasks (handgrip and reactive hyperaemia) were examined in 32 overweight untrained premenopausal women (22.0??0.6 years). In these studies, forearm blood flow (FBF) was assessed using Hokanson Plethysmography with the venous occlusion technique. The surface electrocardiogram and continuous beat-to-beat arterial blood pressure were also monitored. Peak oxygen uptake was assessed using open-circuit spirometry (True Max 2400, ParvoMedics). In addition, body composition was measured using DEXA (dual energy X-ray absorptiometry; DPX-IQ, Lunar Radiation). Results from Study 1 indicate that FBF response to mental challenge in young females was smaller compared to previously obtained data from age-matched males. Furthermore, this FBF response to mental challenge was negatively correlated to insulin resistance estimated by the homeostasis model assessment (HOMA-IR) (r = - .52, p < .05). In addition, when cardiopulmonary baroreceptors were unloaded by a mild level of LBNP (-20 mmHg) during Stoop, FBF response to mental challenge (vasodilation) was abolished suggesting a large dependency of vasodilation response during mental challenge on cardiopulmonary baroreflex. After 15 weeks of supervised HIIE training, aerobic fitness improved (p < .05) whereas percent of body fat was significantly decreased (p < .05). In addition, recovery BP following Stroop was significantly reduced. Insulin resistance (HOMA-IR) was marginally decreased (p = .056). Women who had higher insulin resistance (HOMA-IR) lost less fat than women with lower HOMA-IR (r = .60, p = .088). In addition, change in FBF during Stroop after training was directly related to pretest insulin resistance levels (r = .68, p < .05). Therefore, HIIE training had a normalising effect on FBF response to mental challenge. PEP/LVET ratio at rest and during LBNP was also significantly increased in women with higher HOMA-IR suggesting a reduction in cardiac contractility via a decrease in sympathetic stimulation (r = .62, p = .076, r = .62, p = .75 respectively). In Study 3 results indicated that 12 weeks of the FEM trial significantly reduced percent of body fat (p < .001), fasting insulin (p < .05), interleukin-6 (p < .05) and cortisol (p < .05), and significantly improved aerobic fitness ( ; p < .001). With respect to cardiovascular and cardiac autonomic measures, rate pressure product (RPP) was significantly reduced at rest (p < .05) and during recovery after Stoop (p < .05), suggesting decreased myocardial oxygen consumption. In addition, baseline heart rate determined in the sitting position was significantly reduced (p < .05), while both baseline high frequency power (HF) determined in supine (p < .01) and cardiac baroreflex sensitivity (BRS) determined in the sitting position (p < .05) were increased after the FEM trial. In addition, BRS determined during mental challenge also marginally increased (p = .051). In summary, lifestyle intervention including HIIE training, Mediterranean-style eating plan, and a fish oil supplement significantly enhanced parasympathetic influence of the heart and improved fitness, blood profiles, and body composition.