Dissertations / Theses on the topic 'Cardiovascular and autonomic response'

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.

Hostile sexism is the antipathetic expression of sexism, in which men are antagonistic towards women who threaten their superiority. Benevolent sexism is the patriarchal expression of sexism, where men express protective, yet restrictive, attitudes towards women. Both forms of sexism originate from the view that women are inferior, frail, and only suited for nurturing or domestic responsibilities. Benevolent sexism may be more harmful to women because coping is thwarted by observers' underestimation of its effects (Bosson, Pinel, & Vandello, 2009). The present study aimed to examine women's responses to and recovery from hostile and benevolent sexism utilizing measures of cardiovascular reactivity and recovery. I predicted that women would exhibit greater reactivity to hostile sexism, but impaired recovery to benevolent sexism. Participants were 124 undergraduate women (50% Caucasian, age M = 18.92), with no history of cardiovascular health issues. Sexism condition - benevolent, hostile, or no sexism - was manipulated by exposing participants to comments made by a male experimenter. Cardiovascular responses were obtained during rest, task, and recovery periods. As predicted, women exhibited greater cardiovascular reactivity after exposure to hostile sexism, and women who experienced benevolent sexism showed impaired recovery, compared to the other two conditions. Findings illustrate that hostile sexism elicits immediate responses that resolve relatively quickly. However, benevolent sexism may be more pernicious in terms of psychological and physical health due to its prolonged effects.

Submitted by Nadir Basilio (nadirsb@uninove.br) on 2015-07-20T18:01:54Z No. of bitstreams: 1 Suely Tomimura.pdf: 1781054 bytes, checksum: acaac7dbd088721fbe65530e5cd96c5f (MD5)
Made available in DSpace on 2015-07-20T18:01:54Z (GMT). No. of bitstreams: 1 Suely Tomimura.pdf: 1781054 bytes, checksum: acaac7dbd088721fbe65530e5cd96c5f (MD5) Previous issue date: 2013-12-17
Due to the increasing numbers of Systemic Arterial Hypertension (HBP) patients in population and its senescence, steadily increased from 600 million in 1980 to 1.2 billion in 2008. The World Health Organization (WHO) in 2009 attributed to high blood pressure (BP) was the death cause for 9.5 million people worldwide. Currently, the hypertension has become a serious public health problem. This entity is an important risk factor for congestive heart failure, cerebrovascular disease, acute myocardial infarction, nephropathy, retinopathy and peripheral vascular insufficiency. Studies have suggested that laser photobiomulation, employing a low power, acts into the inflammatory and proliferative phases of tissue repair, by modulating the inflammatory mediators synthesis as same as the Reactive Oxygen Species (ROS). According scientific publications indicate that the inflammation component is closely related to systemic arterial hypertension as well as possibly to the oxidative stress, both participates in the Hypertension genesis. The aim of this study was to verify the long-term effects of Low Level Laser Therapy (LLLT) application in Spontaneously Hypertensive Rats-SHR (Spontaneously Hypertensive Rats) through on cardiovascular autonomic modulation and oxidative stress in the blood. The experiment consisted in 3 phases: Phase I – LLLT irradiation on SHR: The experiment's phase I consisted of animal’s irradiation, when the laser group received three times LLLT applications weekly for a 7 weeks total; the sham group received three times per week of LLLT simulation for 7 weeks and a total of 21 applications. Prospective, randomized, controlled study, with 16 SHR approximately 2 months age, randomly divided into 2 groups : Sham (n = 8) and Laser (n = 8). The animals were irradiated in a prompt, onto the tail’s dorsal area, using a Diode Laser (MMOptics, São Carlos, SP, Brazil) with a wavelength (λ) of 780 ± 2 (nm), output power at 40 mW, with a 0.04 cm2 beam area, dose of 30 J/cm2 power density of 1W/cm2 and irradiation time of 90 s. In Phase II - Hemodynamic and autonomic cardiovascular evaluation: for a period of 7 weeks, consisted in the cannulation procedure, collecting and analysis. The animals were cannulated, evaluated hemodynamically and analyzed the cardiovascular autonomic modulation. Phase III - Oxidative stress analysis, were analyzed: a) protein damage; b) cell membrane damage; c) antioxidant enzyme activity; d) nitrite concentrations. Data from phase II and III were collected and statistically analyzed applying One Way ANOVA test, followed by post hoc Student - Newman Keulls and considering the significance level of p < 0.05, equivalent to an error α 0.05. The results demonstraded hemodynamic parameters of group LLLT treated showed a BP reduction, when compared with the Sham group. In laser group the diastolic arterial pressure (DAP) showed a reduction of -14 mmHg (± 143 * 4 x 157 ± 3 mmHg Sham) and mean arterial pressure (MAP) - 13mmHg (169 ± 4 * x 182 ± 4 mmHg Sham) there were statistically significant difference. Although the value of systolic arterial pressure (SAP) (196 ± 5 x 207 ± 4 mmHg) showed no differences. There was a decreased in resting HR with a statistically significant difference in the laser group compared to Sham (312 ± 14 vs. 361 ± 13 bpm sham). The spectral reviews in the field of time and frequency showed that the Laser group decreased sympathetic activity on the heart and blood vessels while compared to the Sham group. The heart rate variation was analyzed using the DP-PI ( standard deviation of the pulse interval) VAR-PI components (pulse interval variability) and it demonstrated that LLLT was effective in diminishing variation in heart rate (HR) and sympathetic activity in heart, inducing a substantial fall in blood pressure. Lasertherapy presented a rise in spectral low-frequency component in the pulse interval (LF - IP action of the sympathetic at heart), though the sham group showed up exaggeratedly decreasing (6.77 ± 4:35 and 2:31 ± 0:16 ms ² Sham) as a function of saturation variation. Thus, there was a significant reduction in sympathetic activity after LLLT using. A high-frequency band on interval pulse HF-IP (parasympathetic activity) showed no statistically significant differences between the groups and Laser Sham group. The baroreceptor sensitivity, assessed by the alpha index, signalized a significant increase in the Laser (1:07 ± 0:23 vs. 0:45 ± 0:20 ms / mmHg Sham) group, presenting an improvement in the receptors sensitivity. The baroreflex results were associated with other relevant data, the VAR - SAP (49.55 ± 15.94 * vs 70.51 ± 13:55 mmHg² Sham) and SD -SAP (6.94 ± 1.21 * vs 8.68 ± 1.11 mmHg Sham) that proved to be diminished in the laser group, indicating baroreflex improvement sensitivity concomitantly to the positive SAP variation reduction of. There were no significant differences in baseline SAP (196 ± 5 vs. 207 ± 4 mmHg Sham) between the two groups. The results in the oxidative stress and autonomic analysis demonstrated an association between increased NO production (nitrite 0:36 ± 0:03 vs 0:26 ± 0:03 nm / mg Sham) and decreased in the vascular sympathetic (LF - SAP 7.28 ± 1.63 * vs 9.86 ± 0.47 Sham), both leading to a profound vasodilatation then a significant fall in of blood pressure. Lasertherapy shown to alter the plasma parameters such as oxidative nitrite, revealing an NO increased metabolism, as described above and, moreover, accounted for a significant reduction in carbonyl plasma concentration (vs 3.93 ± 0.24, 4.75 ± 0:26 * nm / mg Sham). Our experimental study indicate that LLLT was able to reduce the oxidative stress parameters through diminishing the damage to the proteins. The enzymatic defense was analyzed by the enzyme SOD concentration in blood plasma, denoted that no significant differences (4:42 ± 0:10 4:25 ± 0:06 vs usod / mg) between groups. Thus, low level laser therapy has shown to improve cardiovascular autonomic activity as well as oxidative parameters which resulted in steadily staggeringly reduce the blood pressure of hypertensive animals.
Em razão do aumento populacional e a senescência, o número de indivíduos com Hipertensão Arterial Sistêmica (HAS) cresceu de 600 milhões em 1980 para 1,2 bilhões (OMS 2011). Lim (2012) atribuiu que a pressão arterial (PA) elevada fosse a causa mortis de 9,5 milhões de indivíduos ao redor do mundo. Atualmente, a HAS tornou-se um grave problema de saúde pública. A hipertensão é um importante fator de risco para insuficiência cardíaca congestiva, doenças cerebrovasculares, infarto agudo do miocárdio, nefropatia, insuficiência vascular periférica e retinopatia hipertensiva. Considerando publicações científicas que demonstram que o componente da inflamação e do estresse oxidativo estão intimamente relacionados à gênese da hipertensão arterial sistêmica (HAS), e que o laser com potência baixa tem efeito positivo no estresse oxidativo e apresenta ação antiinflamatória eficaz, desta forma buscamos estudar a resposta da Laserterapia na HAS. Inúmeros estudos vêm sugerindo, ao longo de décadas, que a fotobiomulação pelo laser empregado uma potência baixa, atua durante as fases inflamatórias e proliferativas da reparação tissular, modulando síntese de mediadores inflamatórios e espécies reativas de oxigênio (ROS). O objetivo deste estudo foi analisar os efeitos da aplicação do laser de baixa intensidade em ratos espontaneamente hipertensos SHR (Spontaneously Hypertensive Rats) em longo prazo na modulação autonômica cardiovascular e no estresse oxidativo sangúineo. Estudo prospectivo, randomizado e controlado com 16 ratos SHR, divididos aleatoriamente em 2 grupos: Sham (n=8) e Laser (n=8).O experimento foi dividido em três fases: Fase I – Irradiação dos animais: constituiu-se na irradiação com laser nos animais SHR, onde o grupo Laser recebeu três aplicações semanais de LBI durante sete semanas; já no grupo Sham foram realizados três simulações de aplicação semanais de Laser de Baixa Intensidade (LBI) durante 7 semanas, totalizando 21 aplicações de LBI. Os animais foram irradiados pontualmente, na região dorsal da cauda, utilizando um Laser Diodo (MMOptics, São Carlos, SP, Brasil) com comprimento de onda de λ = 780 ± 2 (nm); potência de 40 mW, área do feixe de 0,04 cm2, densidade de energia de 30 J/cm2, densidade de potência de 1W/cm2, tempo total de irradiação de 90 s de exposição. Fase II – Avaliação hemodinâmica e autonômica cardiovascular: constituiu-se nos procedimento de canulação, registro de dados e coleta de material, teve inicio após sete semanas de irradiação. Os animais canulados foram avalidados de forma hemodinâmica, bem como analisada a modulação autonômica cardiovascular. Fase III – Análises do estresse oxidativo, foram analisadas: a) danos à proteína; b) danos à membrana celular; c) atividade enzimática; d) concentração de nitrito. Os dados da fase II e III foram coletados e analisados estatisticamente através dos testes Anova One Way, seguido de Post Hoc de Student Newman-Keulls, considerando-se o nível de significância p < 0,05, equivalendo a um erro α de 0.05. Os resultados hemodinâmicos do grupo tratado com LLLT denotaram um decréscimo significativo da PA quando comparado com o grupo Sham. A pressão arterial diastólica (PAD) do grupo Laser revelou uma redução de -14 mmHg (143± 4*vs157±3 mmHg Sham) e a pressão arterial média (PAM) -13mmHg (169±4*vs182±4 mmHg Sham), a frequência cardíaca (FC) em repouso (312±14*vs361±13 bpm Sham) revelando uma diferença estatisticamente significante, porém o valor da pressão arterial sistólica(PAS) não mostrou (196±5 x 207±4 mmHg) alterações entre os grupos. As avaliações espectrais no domínio do tempo e da frequencia demostraram que o grupo Laser reduziu a atividade simpática sobre o coração e vasos sanguíneos quando comparados ao grupo Sham. A variação frequência cardíaca foi analisada através dos componentes VAR-IP (variabilidade do intervalo de pulso) e o DP-IP (desvio do intervalo de pulso) que evidenciaram que o LBI foi eficaz no decréscimo variação da FC e da atividade simpática no coração, induzindo assim a queda das pressões arteriais. A laserterapia mostrou um incremento no componente espectral baixa frequência no intervalo de pulso (BF-IP ação do simpático no coração), porém o grupo Sham apresentou-se exacerbadamente diminuído (6.77 ± 4.35 e 2.31±0.16 ms² Sham) em função da saturação da variação desse componente que foi reduzido. Desta forma, houve um importante decréscimo da atividade simpática com o uso do LBI, significando uma importante diminuição dos níveis pressóricos. A banda de alta frequência (AF-IP atividade parassimpática cardíaca) não mostrou diferenças estatísticas significantes entre os grupos Laser e grupo Sham. A sensibilidade dos barorreceptores, avaliada pelo índice alfa, demonstrou um significativo incremento da resposta no grupo Laser (1.07 ± 0.23 vs 0.45 ± 0.20 ms/mmHg Sham), revelando uma melhora na sensibilidade destes receptores. Os resultados dos barorreflexos encontravam-se associados a outro dado relevante, o componente VAR-PAS (49.55 ± 15.94* vs 70.51 ± 13.55 mmHg² Sham) e DP-PAS (6.94 ± 1.21* vs 8.68 ± 1.11 mmHg Sham) que mostrou-se diminuído no grupo Laser, indicando que a melhora da sensibilidade barorreflexa ocorreu, concomitantemente, à redução positiva da variação da PAS. Não houve diferenças estatísticas significantes na PAS basal (196±5 vs 207 ± 4 mmHg Sham) entre os dois grupos. Já os resultados encontrados na análise do estresse oxidativo e autonômica demonstraram uma associação entre o incremento da produção do óxido nitrico (NO) (nitrito 0.36 ± 0.03 vs 0.26 ± 0.03 nm/mg Sham) e redução do simpático vascular (BF-PAS 7.28 ± 1.63* vs 9.86 ± 0.47 Sham), ambos levando a uma vasodilatação com consequente queda dos níveis pressóricos arteriais. A laserterapia mostrou alterar parâmetros oxidativos como as espécies reativas de nitrogênio (RNS reactive nitrogen species), o nitrito plasmático, revelando um aumento do metabolismo do NO, como já descrito anteriormente e denotou uma diminuição significativa da concentração de carbonilas plasmáticas (3.93 ± 0.24 * vs 4.75 ± 0.26 nm/mg Sham). A defesa enzimática foi analisada através da concentração da enzima SOD no plasma sanguíneo, que não apontou diferenças significativas (4.42 ± 0.10 vs 4.25 ± 0.06 usod/mg) entre os grupos. Evidenciamos que o LBI foi capaz de reduzir este parâmetro oxidativo, reduzindo os danos às proteínas decorrente do estresse. Desta forma, concluímos que a laserterapia demonstrou resposta positiva ao melhorar a atividade autonômica cardiovascular e parâmetros oxidativos que resultaram na redução dos níveis pressóricos dos animais hipertensos.

Abstract Autonomic nervous system (ANS) disturbances are common in Parkinson's disease (PD), but also in other Parkinsonian syndromes, especially in multiple system atrophy (MSA). The differentiation between various Parkinsonian syndromes may be difficult, but it is important for prognostic and therapeutic purposes. The aim of this study was to determine the ability of different analysis methods to reveal cardiovascular regulation disturbances in PD and to evaluate the diagnostic capacity of autonomic tests to differentiate between various Parkinsonian syndromes. Furthermore, this study aimed to evaluate the relationships between ANS disturbances and the clinical characteristics of PD. In addition, the cardiac autonomic function was evaluated during various sleep stages for the first time in untreated PD patients by using spectral heart rate variability (HRV) measures to determine possible sleep stage specific cardiovascular regulation disturbances. Cardiovascular autonomic reflexes were evaluated in 62 untreated and newly diagnosed PD patients, 34 PD patients under antiparkinsonian medication, 47 MSA patients and 15 patients with progressive supranuclear palsy (PSP). The usefulness of different analysis methods was evaluated in a subgroup of 32 untreated PD patients. A further 21 untreated PD patients underwent one-night polysomnography for nocturnal heart rate variability analysis. PD patients with hypokinesia/rigidity as their initial onset sign had a significantly lower max-min ratio in the deep breathing test than those patients with tremor as the initial sign. MSA patients showed significant reductions in both HRV and blood pressure responses during orthostatic provocation, whereas PSP patients had normal results. Absolute spectral measures yielded the clearest indicators separating the PD patients from the controls, while the cardiovascular reflexes proved more useful than the normalised spectral HRV measures in revealing the differences between the two groups. HRV was abnormally decreased during non-REM sleep in PD patients but not during REM sleep or the S1 sleep stage. The normalized high frequency power was significantly decreased in PD patients during sleep stages S2-4, while the standard deviation of the R-R intervals was increased during the same sleep stages, possibly corresponding to the increased motility of PD patients during these sleep stages. The clinical characteristics of PD deserve particular attention in connection with ANS disturbances, since autonomic failure seems to be more pronounced in PD patients with hypokinesia/rigidity as their initial sign. The evaluation of the autonomic function may also be helpful in the differential diagnosis of Parkinsonian syndromes. Spectral analysis methods should be implemented in the evaluation of ANS dysfunction to achieve the best possible efficacy in the differentiation of pathological responses from normal ones. Nocturnal analysis of cardiovascular regulation revealed new and interesting features of pathologic HRV in PD patients, thus when HRV is evaluated, the different sleep stages should be analysed separately.

Abstract Neurogenic factors are known to be important in the development of hypertension. Our current knowledge of the role of autonomic nervous system in chronic hypertension is, however, limited. The purpose of the present study was to evaluate the possible abnormalities in heart rate variability (HRV) and baroreflex sensitivity (BRS) in patients with long standing systemic hypertension compared to subjects without evidence of cardiovascular disease. A particular aim was also to examine whether genetic variation in the renin-angiotensin-aldosterone system (RAS) genes have an influence on cardiovascular autonomic regulation. Case-control studies were carried out on a total of 280 normotensive and 214 hypertensive subjects drawn from a random middle-aged population originally recruited for an epidemiologic study of cardiovascular risk factors. The possible association of BRS with the genetic polymorphisms of renin-angiotensin-aldosterone system genes was studied in a cross-sectional study of 315 healthy controls. Genetic associations were also tested in a younger, independent population sample of 66 subjects. The effects of intensified antihypertensive treatment on autonomic cardiovascular control were evaluated in 33 hypertensive patients with poor blood pressure control. Wide interindividual variation in both HRV and BRS was observed in normotensive as well as hypertensive subjects. Overall HRV and autonomic responses to a change in body posture were blunted in long-standing hypertension. Decreased HRV was mainly related to elevated blood pressure and obesity. For the first time in a population-based study, it was confirmed that BRS is impaired in patients with long-standing hypertension despite adequate antihypertensive treatment. In contrast to HRV, BRS was reduced in hypertensive subjects also after adjustment for blood pressure and obesity. BRS also varied widely both between healthy and hypertensive individuals. The wide interindividual variation in the markers of autonomic cardiovascular regulation was not, however, completely explained by demographic variables, cardiovascular risk factors or lifestyle, suggesting a genetic component contributing to HRV and BRS. The polymorphism in the aldosterone synthase (CYP11B2) gene was found to strongly associate with BRS in two independent random populations of apparently healthy subjects. The association was even stronger in the younger population. On the basis of the observations made in the older population, it seems possible that women are protected against the effect of age and blood pressure on BRS and tend to maintain the genomic influence longer. Intensified antihypertensive combination therapy improved blood pressure control and caused regression of left ventricular hypertrophy, and resulted in significant improvements of HRV and BRS. The present study shows that HRV and BRS are altered in long-standing systemic hypertension. Together with age, blood pressure and obesity, genetic factors seem to be important determinants of BRS. However, abnormal autonomic cardiovascular regulation does not seem to be an irreversible phenomenon, but can be partly restored by modern combination antihypertensive therapy.

De nouvelles modalités de réentrainement sont nécessaires pour les patients présentant une sévère limitation à l’exercice tels que les patients souffrant de broncho-pneumopathie chronique obstructive (BPCO). Le pédalage « excentrique », caractérisé par une meilleure efficience, pourrait permettre à ces patients de se réentrainer plus efficacement. Toutefois, les modalités de prescription et les effets du pédalage excentrique méritent d’être étudiés.Chez le sujet sain, nos résultats ont montré un retard de réactivation parasympathique au décours du pédalage excentrique par rapport au concentrique réalisés à même puissance mécanique, avec une influence de la fréquence de pédalage sur les réponses cardio-respiratoires et autonomes. À même puissance métabolique, le pédalage excentrique se caractérise par un stress cardio-vasculaire et respiratoire plus important que lors du pédalage concentrique, et des réponses neuro-végétatives en faveur d’une activité sympathique plus élevée. La fonction vasculaire est altérée à l’issue du pédalage excentrique. Chez le patient atteint de BPCO, comme chez le sujet sain, le pédalage excentrique a un effet tachypnéisant.Nous pensons que la tension musculaire accrue nécessaire en pédalage excentrique à l’atteinte d’une puissance métabolique équivalente à l’exercice concentrique serait à l’origine d’une plus grande activité sympathique et d’une contrainte hémodynamique périphérique, expliquant l’augmentation de la contrainte cardio-vasculaire en pédalage excentrique
New exercise modalities are required for patients severely limited during exercise such as chronic obstructive pulmonary disease patients (COPD). Eccentric “cycling”, characterized by better efficiency, could allow COPD patients to train more effectively. Nonetheless, prescription modalities and effects of eccentric cycling deserve to be more studied.In healthy subjects, our results showed a delayed parasympathetic reactivation after eccentric compared to concentric cycling matched for mechanical power, together with an influence of pedalling frequency on autonomic and cardiorespiratory responses. At similar metabolic power, eccentric cycling is characterized by a greater cardiovascular and respiratory stress than during concentric cycling, and altered autonomic nervous systems responses in favour to greater sympathetic activity. Vascular function is altered after eccentric cycling. In COPD patients, as in healthy subjects, eccentric cycling impose tachypneic breathing pattern.We believe that the higher muscle tension during eccentric cycling necessary to reach metabolic power similar to concentric leads to greater sympathetic activity and peripheral hemodynamic constraint, likely explaining the increased constraints on cardiovascular system during eccentric cycling

Noninvasive assessment of diabetic cardiovascular autonomic neuropathy (AN): Cardiac and vascular dysfunctions resulting from AN are complications of diabetes, often undiagnosed. Our objectives were to: 1) determine sympathetic and parasympathetic components of compromised blood pressure regulation in patients with polyneuropathy, and 2) rank noninvasive indexes for their sensitivity in diagnosing AN. Continuous 12-lead electrocardiography (ECG), blood pressure (BP), respiration, regional blood flow and bio-impedance were recorded from 12 able-bodied subjects (AB), 7 diabetics without (D0), 7 with possible (D1) and 8 with definite polyneuropathy (D2), during 10 minutes supine control, 30 minutes 70-degree head-up tilt and 5 minutes supine recovery. During the first 3 minutes of tilt, systolic BP decreased in D2 while increased in AB. Parasympathetic control of heart rate, baroreflex sensitivity, and baroreflex effectiveness and sympathetic control of heart rate and vasomotion were reduced in D2, compared with AB. Baroreflex effectiveness index was identified as the most sensitive index to discriminate diabetic AN. Four-dimensional multiscale modeling of ECG indexes of diabetic autonomic neuropathy: QT interval prolongation which predicts long-term mortality in diabetics with AN, is well known. The mechanism of QT interval prolongation is still unknown, but correlation of regional sympathetic denervation of the heart (revealed by cardiac imaging) with QT interval in 12-lead ECG has been proposed. The goal of this study is to 1) reproduce QT interval prolongation seen in diabetics, and 2) develop a computer model to link QT interval prolongation to regional cardiac sympathetic denervation at the cellular level. From the 12-lead ECG acquired in the study above, heart rate-corrected QT interval (QTc) was computed and a reduced ionic whole heart mathematical model was constructed. Twelve-lead ECG was produced as a forward solution from an equivalent cardiac source. Different patterns of regional denervation in cardiac images of diabetic patients guided the simulation of pathological changes. Minimum QTc interval of lateral leads tended to be longer in D2 than in AB. Prolonging action potential duration in the basal septal region in the model produced ECG and QT interval similar to that of D2 subjects, suggesting sympathetic denervation in this region in patients with definite neuropathy.

Cardiac parasympathetic tone mediates hypoxic bradycardia in fish, however the specific cholinergic mechanisms underlying this response have not been established. In Chapter 2, bradycardia in zebrafish (Danio rerio) larvae experiencing translational knockdown of the M2 muscarinic receptor was either prevented or limited at two different levels of hypoxia (PO2 = 30 or 40 Torr). Also, M2 receptor deficient fish exposed to exogenous procaterol (a presumed β2-adrenergic receptor agonist) had lower heart rates than similarly treated control fish, implying that the β2-adrenergic receptor may have a cardioinhibitory role in this species. Zebrafish have a single β1-adrenergic receptor (β1AR), but express two distinct β2-adrenergic receptor genes (β2aAR and β2bAR). Zebrafish β1AR deficient larvae described in Chapter 3 had lower resting heart rates than control larvae, which conforms to the stereotypical stimulatory nature of this receptor in the vertebrate heart. However, in larvae where loss of β2a/β2bAR and β1/β2bAR function was combined, heart rate was significantly increased. This confirmed my previous observation that the β2-adrenergic receptor has an inhibitory effect on heart rate in vivo. Fish release the catecholamines epinephrine and norepinephrine (the endogenous ligands of adrenergic receptors) into the circulation when exposed to hypoxia, if sufficiently severe. Zebrafish have two genes for tyrosine hydroxylase (TH1 and TH2), the rate limiting enzyme for catecholamine synthesis, which requires molecular oxygen as a cofactor. In Chapter 4, zebrafish larvae exposed to hypoxia for 4 days exhibited increased whole body epinephrine and norepinephrine content. TH2, but not TH1, mRNA expression decreased after 2 days of hypoxic exposure. The results of this thesis provide some of the first data on receptor-specific control of heart rate in fish under normal and hypoxic conditions. It also provides the first observations that catecholamine turnover and the mRNA expression of enzymes required for catecholamine synthesis in larvae are sensitive to hypoxia. Taken together, these data provide an interesting perspective on the balance of adrenergic and cholinergic control of heart rate in zebrafish larvae.

Acute inhalation of airborne pollutants alters cardiovascular function and has been shown to have its greatest affects on individuals with pre-existing cardiovascular disease. Evidence suggests that pollutant-induced activation of airway sensory nerves via the gating of ion channels is critical to these systemic responses. Here, we have investigated the cardiovascular responses evoked by inhalation of AITC (TRPA1 agonist) and capsaicin (TRPV1 agonist) in healthy Sprague Dawley (SD) and Wistar Kyoto (WKY) rats, and cardiovascular diseased Spontaneously Hypertensive (SH) rats. Inhalation of the agonists by healthy SD and WKY rats caused significant bradycardia, atrio-ventricular (AV) block and prolonged PR-Intervals. Inhalation of TRP agonists caused differential cardiovascular responses in the cardiovascular diseased SH rats, such that the TRP agonists evoked brady-tachy with AV block and premature ventricular contractions (PVCs). Bradycardic responses to AITC were inhibited by the TRP channel blocker ruthenium red and the muscarinic antagonist atropine, but atropine did not prevent the tachycardic responses seen in the SH rats. Adrenergic inhibition with atenolol prevented the tachycardic responses, but did not prevent the bradycardic responses evoked by AITC in the SH rats. In healthy rats, AITC inhalation also caused a biphasic blood pressure response: a brief hypertensive phase followed by a hypotensive phase, while evoking hypertension in the SH rats. Atropine accentuated the hypertensive phase in all animals, while preventing the hypotension in the healthy animals. In all animals, AITC-evoked heart rate responses were not abolished by terazosin, the [U+F061]1 adrenoceptor inhibitor, which prevented the hypertensive responses. Anesthetics had profound effects on AITC-evoked bradycardia and AV block, which was abolished by urethane, ketamine and isoflurane. Nevertheless, AITC inhalation caused bradycardia and AV block in paralyzed and ventilated rats following pre-collicular decerebration. In conclusion, we provide evidence that activation of TRP channels expressed on nociceptive airway sensory nerves causes significant cardiovascular effects in healthy rats via reflex modulation of the autonomic nervous system (ANS), and that these effects are exacerbated in cardiovascular diseased rats.

The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on January 5, 2010). Thesis advisor: Paul J. Fadel. "December 2009" Includes bibliographical references.

Does having a positive family history of essential hypertension predispose one to greater cardiovascular reactivity? Could reactivity be assessed with stress tasks that have greater external validity than traditional laboratory stressors? To answer these questions? 2b subjects with parental history of essential hypertension and 3b subjects without) were induced to converse with an experimenter on (a) a neutral topic (the weather)? and (b) an affective topic (a frustrating person or event). The topics were selected from a Iist of 2b because they had been rated by undergraduates as being the least and most arousing topics to talk about with a stranger in an experimental situation. The ratings yielded no interactions of sex of experimenter with sex of the subject. Subjects also performed a mental arithmetic task which is a standard laboratory stressor. The order of task presentation was randomly assigned within groups but matched across groups and sex to control sequence effects. For each subject? a 15-minute base I ine period was al lowed before each task. Readings of blood pressure? heart rate and rate of respiration were made at minute one? three? and five of each task phase. Each conversation task consisted of five minutes of talking followed by Iistening for five minutes to the experimenter. The tasks were separated by five-minute intervals to allow return to baseline levels. Results indicated that compared to individuals without parental history of hyper tension? individuals with parental history displayed higher levels of blood pressure (but not heart rate and rate of respiration) whether talking or listening. When peak values were considered; positive parental history subjects showed greater reactivity to the affective topic on diastolic blood pressure. The results also indicated that the three kinds of stressors yielded different levels of physiological responses with the math task and talk phase of the affect task yielding higher levels of blood pressure and heart rate than talk about the weather. The difference between the math and affective tasks was not significant on systolic blood pressure? but math yielded higher responses on heart rate and lower responses on diastolic blood pressure than talking about a frustrating event or person. These results suggest that a more generalizabIe stress stimulus such as an affect-laden conversation? can be reasonably standardized across subjects and elicits an aIpha-adrenergic vaso-constrictive response? a response more readily given by individuals with positive parental history than individuals without. The results also suggest that individuals with positive parental history of hypertension have higher blood pressure levels than individuals without. With respect to the similarity of the findings of this study? with those of other studies which have used older populations? it is proposed that these results are generalizable to older populations and provide evidence that a positive family history of essential hypertension may be considered a risk factor for later cardiovascular disease.
Arts, Faculty of
Psychology, Department of
Graduate

The goal of this study was to build on the historic use of the avian model of development and also to further the knowledge of autonomic nervous system (ANS) regulation of cardiovascular function in vertebrates. Vasoactive drugs sodium nitroprusside, a vasodilator and phenylephrine, a vasoconstrictor were used to study the correlation of cardiovascular function relationship with nerve activity, both sympathetic and parasympathetic (vagal). Additionally, ANG II was used to assess its effects on vagal inhibition. The present study shows that pharmacologically-induced hypertension is associated with a fall in mSNA, indicating that the capacity for sympathetic autonomic cardiovascular regulation is established by late incubation however, late-stage embryonic chickens did not show a significant increase in mSNA during hypotension. The hypotensive response of the embryo was not accompanied by the expected inhibition of vagal discharge; however a slight but insignificant reduction in vagal discharge was noted. When vagal efferent output was isolated, a significant drop in vagal efferent activity was noted in response to hypotension. The present study showed late-stage embryonic chickens lack a vagal response to hypertension in both efferent and sensory limbs. In this study, vagal discharge was reduced from baseline levels in response to Ang II. Collectively, the present study indicates that the lack of a decreased heart rate, in response to increases in Pm caused by Ang II, is due to a central inhibitory action of Ang II on the vagus. Data from the present study suggests that although autonomic interaction with the cardiovascular system in present in late-stage chicken embryos, it is still underdeveloped and possesses a limited capacity.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1995.
Includes bibliographical references (p. 92-95).
by Ramadrishna Mukkamala.
M.S.

The goal of this study was to build on the historic use of the avian model of development and also to further the knowledge of autonomic nervous system (ANS) regulation of cardiovascular function in vertebrates. Vasoactive drugs sodium nitroprusside, a vasodilator and phenylephrine, a vasoconstrictor were used to study the correlation of cardiovascular function relationship with nerve activity, both sympathetic and parasympathetic (vagal). Additionally, ANG II was used to assess its effects on vagal inhibition. The present study shows that pharmacologically-induced hypertension is associated with a fall in mSNA, indicating that the capacity for sympathetic autonomic cardiovascular regulation is established by late incubation however, late-stage embryonic chickens did not show a significant increase in mSNA during hypotension. The hypotensive response of the embryo was not accompanied by the expected inhibition of vagal discharge; however a slight but insignificant reduction in vagal discharge was noted. When vagal efferent output was isolated, a significant drop in vagal efferent activity was noted in response to hypotension. The present study showed late-stage embryonic chickens lack a vagal response to hypertension in both efferent and sensory limbs. In this study, vagal discharge was reduced from baseline levels in response to Ang II. Collectively, the present study indicates that the lack of a decreased heart rate, in response to increases in Pm caused by Ang II, is due to a central inhibitory action of Ang II on the vagus. Data from the present study suggests that although autonomic interaction with the cardiovascular system in present in late-stage chicken embryos, it is still underdeveloped and possesses a limited capacity.

Recent reports suggest that human immunodeficiency virus (HIV), the virus causing AIDS, may cause autonomic nervous system (ANS) dysfunction. ANS abnormalities on cardiovascular reflex tests have been demonstrated in HIV+ persons, persons infected with HIV, who have signs of illness or have used intravenous drugs. In this study the cardiovascular reflex function of 11 HIV+ homosexual or bisexual males meeting the Centers for Disease Control criteria for absence of illness was compared to that of 11 uninfected homosexual or bisexual males of similar ages. Somatic, depression and fatigue differences between groups were assessed using an ANS symptom checklist, the Beck Depression Inventory (BDI) and the Profile of Mood States (POMS). Six of the 11 HIV+ subjects were impaired on the cardiovascular reflex tests. Differences on the BDI and POMS were not attributable to a depressive mood or despair, but rather to presence of mild symptoms of HIV infection and fatigue.

Abstract Ischemic stroke is associated with cardiovascular autonomic nervous system (ANS) disturbances, including reduced heart rate (HR) variability and acute phase neurohumoral activation with elevated stress hormone levels. The impact of HR variability and neurohumoral factors such as natriuretic peptides on the long-term survival of patients with ischemic stroke has not been studied previously. This study was designed to evaluate cardiovascular autonomic regulation in ischemic stroke patients by assessing HR dynamics and various neurohumoral factors. The values of the assessed variables in predicting mortality were evaluated. HR variability assessments were performed in the acute phase of ischemic stroke and for a general elderly population. Various neurohumoral factors were also assessed in the acute phase of stroke. After follow-up, the survival of the subjects was assessed and the prognostic values of the measured factors were evaluated. Stroke patients were found to have cardiovascular autonomic and hormonal disturbances manifested as reduced traditional time and frequency domain measures of HR variability, altered long-term HR dynamics and elevated levels of natriuretic peptides in the acute phase. Altered long-term HR dynamics in the acute phase of stroke predicted long-term mortality after stroke and cerebrovascular mortality in the general elderly population. Neuroendocrine activation involving elevated natriuretic peptide values that were associated with high cortisol and catecholamine levels was observed in the acute phase of ischemic stroke. Neurohumoral disturbance was prognostically unfavourable. The most powerful predictors of poststroke mortality were altered long-term HR dynamics and elevated levels of natriuretic peptides and cortisol, which predicted mortality independently of the conventional risk factors in multivariate analysis. Prognostically unfavourable cardiovascular autonomic dysfunction with disturbances in the long-term behaviour of HR dynamics was found to be related to ischemic stroke. Neurohormonal activation with elevated natriuretic peptide and cortisol levels in the acute phase predicts long-term mortality after ischemic stroke.

Thesis (Ph. D.)--Ohio State University, 2003.
Title from first page of PDF file. Document formatted into pages; contains xiii, 127 p.; also includes graphics Includes bibliographical references (p. 91-105). Available online via OhioLINK's ETD Center

Heart Rate Variability describes the beat-to-beat variation in heart rate arising from activity of the sympathetic and parasympathetic branches of the Autonomic Nervous System (ANS). Reduced ANS tone measured by reduced heart rate variability (HRV) is a powerful predictor of adverse diagnosis in patients and is associated with increased mortality. Published research suggests that inflammation has a deleterious effect on Autonomic Nervous System tone. This study aimed to: establish if mild inflammatory conditions are associated with changes in autonomic tone as defined by heart rate variability studies in the following conditions: a. Influenza vaccination b. Reduction in oesophageal inflammation c. Reduction in weight The aim of the first study was to assess the link between inflammation resulting from the influenza vaccination and the associated changes on heart rate variability. 71 healthy volunteers opting to have a routine influenza vaccination were investigated for potential changes in cardiovascular autonomic tone associated with the temporary inflammatory effects of an Influenza vaccination. A number of temporal and frequency domain parameters of heart rate and breathing were assessed 2-5 days prior to vaccination and 1-4 days post vaccination. A sub-group of 15 volunteers who reported significant symptomatic reaction to the vaccination for at least 24 hours following vaccination displayed a statistically significant (p=<0.02) reduction in five of the six HRV parameters obtained during metronome-guided breathing. There was no evidence of significant reduction in autonomic tone following vaccination in the full sample of 71 volunteers. The aim of the second study was to establish whether inflammation resulting from erosive or non-erosive oesophagitis caused by gastro-oesophageal reflux disease had any association with changes in heart rate variability. 12 volunteers with non-erosive oesophageal reflux disease (NERD) and 8 with erosive oesophageal reflux disease (ERD) were investigated for HRV after initial diagnosis under gastroscopy. HRV assessment was repeated following 8 weeks of treatment with a proton-pump inhibitor (PPI). Initial reflux symptoms and response to PPI treatment were assessed using the GERD Impact Scale questionnaire. All participants had effective symptom response to treatment and there was no significant difference insymptoms score between NERD and ERD groups. There was a small but statistically significant increase in HRV detected following PPI treatment in the ERD group (p=0.05). The aim of the third study was to assess the link between obesity / pro-inflammatory adiposity, weight loss and the associated changes in heart rate variability. 38 clinically obese volunteers (BMI 30-39) with a family history of diabetes were reviewed for HRV prior to and following a lifestyle intervention designed to reduce body weight and BMI. Volunteers underwent repeated HRV studies after 4 months and 8 months of treatment. Volunteers on average achieved a weight loss of 11.5% (±6.0). There were statistically significant changes in HRV parameters in sub-group A (BMI ≥36) and correlation of biochemical measures with weight loss. These results further elucidate the effect of mild inflammatory triggers on autonomic tone as measured by HRV. These effects and their significance are discussed in detail in this document. The significance of the ‘cholinergic anti-inflammatory pathway’ is discussed with respect to the inflammatory conditions investigated. Suggestions for further work are proposed. In conclusion it is entirely possible to measure subtle changes in heart rate variability associated with mild inflammation and that on the evidence presented here these changes in heart rate variability are hypothesised to be reversible. My original contribution to knowledge is: 1. Changes in heart rate variability are associated with low grade inflammation resulting from the Influenza vaccination, erosive oesophagitis and increased adiposity. 2. Measurement of subtle changes in autonomic tone, associated with inflammatory challenges is possible and concurs with other published research. 3. The level of HRV attenuation does appear to be linked to those with a higher level of inflammation. In each study the most significant results came from subgroups of volunteers either demonstrating: a higher level of symptom severity, erosive oesophagitis or were in a subgroup of participants with the highest BMI / adipose tissue. 4. In the early stages of reduced heart rate variability we see that concurrent reduction in inflammation is associated with an increase in autonomic tone.

Following cervical or upper thoracic level spinal cord injury (SCI), motor, sensory and autonomic systems are disrupted. One form of this autonomic dysfunction is the condition autonomic dysreflexia (AD), which is characterised by episodes of high blood pressure in response to afferent input from regions below the injury level. An animal model of autonomic dysreflexia, the T4 transected rat, was used in this thesis to gain insight into the cardiovascular and temperature components of the disorder, possible peripheral mechanisms and interventions to prevent its development. Chapter 2 of the thesis includes the charaterisation of a T4 transection rat model of spinal cord injury. This characterisation includes confirmation of decreased baseline mean arterial pressure (MAP, 71 down from 117 mmHg) and elevated heart rate (HR, 431 bpm from 366 bpm) for 6 weeks post injury (p.i.). Documentation of the development of AD found that hypertensive responses were fully developed (+20 mmHg) by 4 weeks p.i. Further, during episodes of AD at Weeks 4 and 5 p.i., tail surface temperatures decreased significantly (mid-tail, -1.7oC), indicative of extensive vasoconstriction. Comparison of vascular responses of intact and SCI animals to adrenergic agonists (phenylephrine, PHE and methoxamine, METH) following ganglionic blockade in vivo found that SCI animals experienced prolonged vasoconstriction in blood vessels above and below injury level in response to PHE but not METH. Possible mechanisms of this change included decreased neuronal reuptake of PHE (METH is not a substrate for neuronal reuptake). The presence of prolonged vasoconstriction in blood vessels throughout the body, not just regions below injury level, suggests a widespread mechanism for the change, such as the decreased basal MAP, norepinephrine levels or neural activity present following injury. Thus, it was hypothesised that increased activity from an early stage post injury may prevent the peripheral adaptation and perhaps hinder development of AD. For this, the common rehabilitation technique, treadmill training, was used. Surprisingly, rather than preventing AD, the training actually accelerated its development, producing exaggerated hypertensive responses to colorectal distension (CRD) at Weeks 3 and 4 post-injury (Week 4, Trained: +38.5 ?? 1.5 mmHg; Sedentary: 23.4 ?? 3.1mmHg). Comparison of vascular responses of both groups to PHE injection found no significant difference indicating that the enhanced responses were not a result of peripheral vascular changes. Investigation of the central morphology following SCI, made via immunohistochemical processing of the post-mortem spinal cords, found that Treadmill Trained SCI animals had elevated calcitonin gene related peptide (CGRP) immunoreactivity within lamina III/IV of lumbar segments, compared to intact cords. It is possible that this finding indicates afferent sprouting that may have accelerated the development of AD in Treadmill Trained animals. The results within this thesis highlight the importance of awareness and examination of autonomic function in SCI patients, especially those undergoing rehabilitative training.

Cardiovascular disease is the leading cause of mortality in the developed world with up to fifty percent of cases being due to sudden cardiac death. Changes in sympatho-vagal balance underpin many cardiovascular conditions including heart failure and myocardial infarction. Neuraxial modulation of the autonomic nervous system is an emerging therapy to prevent ventricular arrhythmias, the main cause of sudden cardiac death. Chapter One reviews our current understanding of how the cardiac autonomic nervous system influences ventricular arrhythmogenesis. A particular focus was on the controversial role of cholinergic receptors and nitric oxide (NO) in parasympathetic protection from ventricular arrhythmias. Tetrahydrobiopterin (BH₄), a critical cofactor for both tyrosine hydroxylase and NO synthases, and the co-transmitter neuropeptide-Y (NPY) may also influence sympathetic triggering of ventricular arrhythmias. This leads to the specific aims of the thesis which were to determine the mechanisms of the cholinergic antifibrillatory effect, investigate the role of cotransmission in arrhythmogenesis and, the mechanistic role of BH4 in autonomic cardiovascular control. Chapter Two detailed the experimental approach taken to investigate the hypotheses. A novel Langendorff heart preparation was developed with intact autonomic nerves to investigate how the stable analogue of acetylcholine, carbamylcholine (CCh) raises ventricular fibrillation threshold (VFT) and whether exogenous or endogenously released NPY lowers VFT. These actions are further investigated using optical mapping, dye free imaging of ventricular cell monolayers, immunohistochemistry, ELISA assays and measurements of NO metabolite production. To investigate the role of BH4 in the sympathetic control of the heart, an IRES-cre recombinase strategy was used to produce genomic deletion of GCH1 (the gene encoding BH4) in sympathetic neurons. Biopterins and plasma catecholamines were measured using HPLC, and blood pressure and heart rate via tail cuff plethysmography. Chapter 3 showed that CCh increased VFT, prolonged action potential duration and flattened the electrical restitution curve. This effect required stimulation of both muscarinic and nicotinic receptors and the generation of nNOS derived NO utilising a cGMP dependent pathway. These observations are in keeping with established evidence demonstrating the obligatory role of the muscarinic receptor and indicate that the role of NO is likely to be via modulation of cholinergic neurotransmission. Chapter 4 studied the role of the sympathetic co-transmitter NPY. NPY has been shown to increase ventricular myocyte calcium dynamics. Plasma levels are also increased post myocardial infarction and during heart failure, and correlate with outcomes. Perfusion of NPY decreased VFT via a Y1 receptor dependent mechanism and increased arrhythmic activity in myocyte monolayers. Direct sympathetic stimulation resulted in NPY release and remained pro-arrhythmic despite β-blockade, an effect that could be abolished by combined β-Y₁ receptor blockade. These observations indicated that NPY may be a novel, pro-arrhythmic trigger amenable to therapeutic pharmacological modulation. Chapter 5 details the generation and phenotyping of two tissue specific Gch1 knockout mouse models. Whilst one model failed to produce significant lowering of BH₄ in sympatho-adrenal tissue, the other did result in a marked neuro-motor phenotype. A biochemical rescue or alternative genomic modification approach would be required to study the cardiovascular phenotype of sympathetic Gch1 deletion in more detail. Chapter 6 is a concluding discussion summarising the main findings of the thesis, placing them in a clinical context and discussing avenues for further research.

This experiment investigated lateralized hemispheric regulation of the autonomic nervous system (ANS) among high anxious and nonanxious university undergraduate men using a novel laboratory paradigm. Specifically, this three phase paradigm entailed the administration of a verbal fluency (left frontal) and nonverbal fluency (right frontal) task with or without the threat of a painful stimulus (cold pressor) to high anxious and nonanxious participants. Thus, the cerebrums are hypothesized to be engaged in a dual-task experience requiring the regulation of the ANS and concurrent performance on the verbal or the nonverbal fluency measure. Given the literature which supports relative right hemisphere activation among anxious individuals, it was hypothesized that high anxious men would (1) demonstrate greater physiological arousal to the cold pressor, (2) perform relatively worse on nonverbal fluency measures and demonstrate greater difficulty regulating cardiovascular functioning, and (3) demonstrate relatively lower nonverbal fluency scores and increased physiological arousal when presented with the nonverbal fluency task and cold pressor stimulus simultaneously. The results are evaluated using three perspectives: Heller's (1993) hypothesis, Kinsbourne's Functional Cerebral Distance principle, and lateralized regulation of the sympathetic and parasympathetic nervous system. The results only partially supported the right hemisphere activation hypothesis for anxious individuals, as many of the significant results were counter to hypotheses. Specifically, high anxious men demonstrated lower verbal fluency scores and greater heart rate during the combined stimulus of the cold pressor and verbal fluency task. The data are supportive of relative anterior deactivation among high anxious men. The discussion extends the findings to present questions regarding cerebral regulation of the ANS. Future experiments which may add to the current understanding of lateralized regulation of the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) are suggested.
Ph. D.

Defensive hostility has been attributed as an early risk factor of coronary heart disease. The autonomic characteristics of high defensive, high hostile (HD) and low defensive, high hostile (LD) men and women were assessed with a variety of cardiovascular (CV) measures. Reactivity and recovery to an active laboratory stressor (video game, VG) and a passive laboratory stressor (hand cold pressor, CP) of 15 HD men, 16 LD men, 16 HD women, and 16 LD women were recorded. It was predicted that the CV patterning associated with the HD participants would display more sympathetic and less vagal control as well as the least pronounced recovery from the stressors in comparison to LD participants. Results revealed differential CV responses to the lab tasks by group. HD women displayed consistently high levels of low frequency power heart rate variability (HRV) during baseline and across conditions. HD men exhibited significantly pronounced heart rate reactivity and reduced high frequency power HRV to the CP task in comparison to LD men. Interestingly, LD women displayed weaker blood pressure (BP) recovery to the VG in comparison to HD women, whereas the opposite pattern was observed in BP recovery to the CP. These results suggest that defensiveness and sex may moderate the CV reactivity and recovery to different types of stressors in hostile participants.
Master of Science

Anxiety and its cognitive component of worry have been related to exaggerated cardiovascular reactivity and delayed recovery to laboratory stressors, and to increased risk of cardiovascular disease. Previous research on the anxiety-cardiovascular system relationship, including data from Knepp and Friedman (2008), are included to support this project. Two experiments were completed during the course of this study. The first consisted of two peripheral-based body positioning tasks. The second experiment used an active versus passive sympathetic stress task paradigm (mental arithmetic, hand cold pressor). Subjects were nonsmokers free of cardiovascular and neurological disease. Trait worry was examined through the Penn State Worry Questionnaire (PSWQ). Blood pressure recordings and cardiac recordings through ECG and ICG were done in each experiment during seven epochs: an anticipatory baseline with three baselines preceding and three recovery periods following each task. Repeated measures analysis was run on all cardiovascular measures. In the first experiment, high worriers had worsened blood pressure reactivity to task. The second experiment found that high worriers had increased stroke volume across all epochs. There were mixed findings in the studies relating to subjects acclimated to the laboratory experience. Future directions of research relating anxiety, worry, and cardiovascular risk factors are discussed.
Ph. D.

The influence of autonomic activation in response to controllable versus noncontrollable stress, anger imagery induction, and relaxation imagery was studied among 80 participants between the ages of 18 and 34. Participants differed in level of trait hostility as assessed by the Irritability Subscale of The Buss-Durkee Hostility Inventory (Buss & Durkee,1957) and the Ho scale of the Cook-Medley Hostility Inventory (Cook & Medley, 1954). Groups were further subdivided with regards to either having a positive family history of cardiovascular disease or having no significant history. Results were obtained through analyses of electrocardiograph R-R intervals which produced an index of autonomic nervous system activation. Findings supported hypotheses involving the relations between autonomic balance and stress and hostility for the female and male populations. Among both populations, parasympathetic regulation was diminished during anger induction for individuals with high levels of trait hostility and having a family history of cardiovascular disease. Similar results were obtained for men during relaxation imagery induction.

The skin conductance response is involved in the preparation for and response to stimuli with emotional significance. The neural mechanisms responsible for the generation of the skin conductance response are not well understood despite the common use of this signal as an index of emotional response. Data from anatomical, lesion, and neuroimaging studies in humans suggest that the amygdala, a component of the brain circuit for emotion, plays a critical role in the generation of the skin conductance response. Here we employ a novel combination of existing techniques to understand the stimuli that elicit skin conductance responses in the monkey and the neural mechanisms in the amygdala that participate in its generation. We recorded skin conductance responses in monkeys trained to perform a passive image viewing task. This paradigm is a staple of human emotion research but to date has not been adapted to the monkey. In addition, skin conductance responses to these stimuli were recorded in conjunction with single unit responses from the amygdala. This study addresses the relationship between the activity of single neurons recorded from identified nuclei of the monkey amygdala and autonomic responses. Neurons in multiple nuclei of the amygdala showed reliable changes in neuronal discharge prior to the skin conductance response. These neurons were primarily in the dorsal nuclei of the amygdala, which confirms predictions made from anatomical and neuroimaging data. It is suggested that these changes in neuronal discharge may correspond to the generation of this autonomic component of the expression of emotion.

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2007.
Includes bibliographical references (p. 95-98).
The human cardiovascular system routinely encounters conditions that cause it to adapt. For example, when an astronaut enters microgravity, his/her cardiovascular system adapts rapidly to the weightless environment with no functional impairment. This adaptation is entirely appropriate while in space. However, it predisposes astronauts to problems when they return. It has been suggested that the regimen for astronauts on long-duration space travel include periods of artificial acceleration via centrifugation, in order to maintain some exposure to a gravitational gradient and thus ameliorate some of the physiological consequences of exposure to microgravity. To design such an intervention, it is desirable to know and understand, as well as to predict the cardiovascular response to centrifugation stress. A reasonably compartmentalized mathematical model of the cardiovascular system that represents these conditions is presented, which will allow for understanding and predicting cardiovascular behavior under such conditions. We validated our simulations against human data and showed that our results closely matched the experimental data. Upon validation, we used our model to predict the response of the cardiovascular system to levels of stress that cannot yet be tested on human subjects.
by Sam Ahmad Zamanian.
S.M.

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2004.
Includes bibliographical references (p. 163-185).
The cardiovascular response to changes in posture has been the focus of numerous investigations in the past. Yet despite considerable, targeted experimental effort, the mechanisms underlying orthostatic intolerance (OI) following spaceflight remain elusive. The number of hypotheses still under consideration and the lack of a single unifying theory of the pathophysiology of spaceflight-induced OI testify to the difficulty of the problem. In this investigation, we developed and validated a comprehensives lumped-parameter model of the cardiovascular system and its short-term homeostatic control mechanisms with the particular aim of simulating the short-term, transient hemodynamic response to gravitational stress. Our effort to combine model building with model analysis led us to conduct extensive sensitivity analyses and investigate inverse modeling methods to estimate physiological parameters from transient hemodynamic data. Based on current hypotheses, we simulated the system-level hemodynamic effects of changes in parameters that have been implicated in the orthostatic intolerance phenomenon. Our simulations indicate that changes in total blood volume have the biggest detrimental impact on blood pressure homeostasis in the head-up posture. If the baseline volume status is borderline hypovolemic, changes in other parameters can significantly impact the cardiovascular system's ability to maintain mean arterial pressure constant. In particular, any deleterious changes in the venous tone feedback impairs blood pressure homeostasis significantly. This result has important implications as it suggests that al-adrenergic agonists might help alleviate the orthostatic syndrome seen post-spaceflight.
by Thomas Heldt.
Ph.D.

There has been concern and controversy in recent years pertaining to the effects that video games have on the player. This study examined physiological and psychological responses to video game play, as well as the interplay between the two domains of response. The primary purpose of this study was to determine if there is a difference in cardiovascular response (measured by heart rate and blood pressure levels) between aggressive and nonaggressive video game play. In addition, self-report of perceived arousal and hostility levels were assessed following completion of both levels of video game play. Physiological resting baselines for heart rate and blood pressure were determined prior to both levels of play. A mean heart rate was recorded for each 2-min interval while 16 male participants played both an aggressive and a nonaggressive video game for a period of 18- min each. Blood pressure levels were again assessed postplay. Following each level of video game play psychological tests (perceived arousal and hostility levels) were administered. Results show a main effect for type of video game on heart rate, with heart rate significantly higher in the aggressive game than in the nonaggressive game. In addition, a main effect for intervals was also significant, with heart rate increasing over time. No siqnificant differences were found between levels for blood pressure, perceived arousal, and hostility scores. The only significant correlation resulted between post-diastolic blood pressure measure and the hostility subscale of the Multiple Affect Adjective Check List. Implications for future research are discussed.

Abstract Epilepsy is associated with changes in autonomic cardioregulatory function. Ictally, autonomic disturbances may be evident with significant changes in heart rate (HR), blood pressure (BP) and respiration. However, interictal dysfunction of autonomic cardiovascular system may be subtle and it may be recognized only by delicate tools designed for that purpose. The aim of this study was to evaluate the function of the cardiovascular autonomic regulatory system in patients with epilepsy. Cardiovascular reflex tests were performed on patients with partial or idiopathic generalized epilepsies. Special attention was paid to temporal lobe epilepsy (TLE). An association of refractory and well controlled TLE and hippocampal sclerosis with altered cardioregulation was evaluated by using cardiovascular reflex tests and an analysis of spectral and non-linear analysis of heart rate variation (HRV). Cardiovascular reflexes were altered both in patients with partial and idiopathic generalized epilepsies who had been treated for epilepsy with antiepileptic drugs (AEDs), whereas patients with newly, untreated epilepsy did not differ from the control subjects. Diminished cardiovascular reflexes also seemed to be associated with carbamazepine (CBZ) treatment. Various parameters of cardiovascular reflex tests and analysis of spectral and dynamic measures of HRV were diminished in patients with TLE compared to the control subejcts. These results indicate that epilepsy, especially TLE, is associated with interictal changes of autonomic cardioregulation. Although these changes seem to be evident in patients with severe form of TLE, patients with well controlled TLE and patients without hippocampal sclerosis also have altered autonomic cardioregulatory function. These results suggest that dysfunction of the cardioregulatory system is rather associated with functional than structural changes of the inner temporal lobe in patients with TLE.

The clinical utility of electrodermal response measures as a predictor of outcome from traumatic vegetative state was investigated. Electrodermal potential data were obtained from five subjects in acute vegetative state at 1 to 3 months post-trauma (Acute group), five subjects in persistent vegetative state at more than 1 year post-trauma (PVS group), five subjects who were more than 1 year post-trauma and had recovered from vegetative state (RVS group), and 10 normal subjects (Control group). Measures included startle response amplitude, baseline lability, habituation and orientation to tones, responses to famous faces and written commands, and total number of skin potential responses. In addition, subjects in the Acute group were reassessed with respect to clinical outcome at 6 months post-trauma. Results revealed significant group differences between the Control group and each of the brain-injured groups in startle response amplitude, baseline lability, and total number of responses. The RVS group had significantly larger startle response amplitudes than the PVS group. Some subjects in the PVS group and all subjects in the Acute group exhibited no startle response on one or more days of testing. Significant group differences also were found for habituation and orientation. Habituation was present in 80% of the Control and RVS subjects, 20% of the Acute subjects and 0% of the PVS subjects, and orientation was present in 80% of the Control subjects, 20% of the Acute and RVS subjects and 0% of the PVS subjects. Group variance in startle response amplitude, baseline lability and total number of responses was significantly greater in the Control group compared with the brain-injured subject groups. In the Acute group, a larger startle response amplitude, greater baseline lability, a greater total number of electrodermal responses, and habituation and orientation were associated with a positive outcome at 6 months post-trauma. These results indicate electrodermal responsiveness is generally reduced following traumatic brain injury, even in subjects with a relatively good recovery from vegetative state. Greater electrodermal activity in early vegetative state may be associated with better potential for recovery.

The dynamic behaviors of a complex organism are explained via voluntary and involuntary action. One underpinning of this system is organized and facilitated by the autonomic nervous system, integrating information from conscious and non-conscious centers in a seemingly hierarchical fashion. As a result, voluntary actions have the ability to inhibit reflexive actions via an inhibitory circuit. 111 subjects performed four diverse autonomic tasks consisting of voluntary and involuntary combinations. Analysis supports the proposed hierarchical model. Each task evoked specific autonomic states. Voluntary tasks influenced autonomic actions more than involuntary tasks. And working memory capacity mediated voluntary control.
Master of Science

Interoception, the perception of the body's physiological state, is often studied in relation to emotion processing. Particularly, cardioception has been largely implicated in anxiety. Three related but distinct dimensions of interoception have recently emerged in the literature: sensibility (IS), accuracy (IAC), and awareness (IAW). Divergent findings regarding interoception and anxiety may result from lacking appreciation for interoceptive dimensions. Additionally, the role of cardiovascular afferent feedback in anxiety and interoception is largely unknown. Baroreflex sensitivity (BRS) has been implicated in interoceptive processes yet no known research directly measures this in relation to multidimensional cardioception. The present study aimed to assess the degree to which IS, IAC, IAW, and BRS predict trait anxiety at rest and during anticipatory anxiety. Results partially suggest increased IAC and BRS, but more variable IS and IAW in relation to trait anxiety. Overall, results show complex associations among factors, suggesting increased specificity among the constructs. Results highlight the importance of attention to construct validity and method variance in the study of interoceptive subdomains. Finally, the present study helps to pave the way for continued investigations concerning cardioception in enduring anxiety and the related role of the baroreflex in cardiac afferent processes.
PHD