<p>Heart rate variability (<b>HRV</b>), or the variation in time between adjacent heart beats over time, is a non-invasive proxy measure of autonomic nervous system (<b>ANS</b>) function that has been used regularly in studies focused on evaluating livestock stress and welfare. The autonomic nervous system regulates involuntary physiological processes (<i>e.g.</i> respiration and heart rate) and consists of two main components, the parasympathetic (<b>PNS</b>), and sympathetic (<b>SNS</b>) branches, which act to maintain bodily homeostasis (PNS) or stimulate the “fight-or-flight” response after exposure to a stressor (SNS). Traditional linear HRV measures provide an estimation of overall autonomic activity or changes to the balance between the PNS and SNS branches by evaluating changes to the mean, variance, or frequency spectra of the R-R intervals. </p><p>To interpret HRV data obtained via linear HRV measures, particularly spectral HRV analysis, a linear assumption has to be assumed where SNS and PNS activity act in a purely antagonistic manner. However, this assumption is not always met. In many cases, ANS activity is altered in a nonlinear manner, which is reflected to some degree in the variability of heart rate output. Therefore, HRV measures that evaluate nonlinear changes to organizational or structural aspects of the R-R interval variability may be a useful compliment to traditional linear HRV measures for distinguishing between stressed and non-stressed states. The purpose of this dissertation was to evaluate the use of nonlinear HRV measures for evaluating dairy calf disbudding pain, piglet castration pain, growing pig heat stress, and as potential indicators of the subsequent immune response to a lipopolysaccharide (<b>LPS</b>) challenge in growing pigs.</p><p>Chapter 1 provides a knowledge base for understanding HRV and its use as a measure of autonomic stress in studies with livestock species. A brief explanation of animal welfare science, measures used to evaluate an animal’s welfare, and a demonstration of need for non-invasive physiological measures is provided before discussing the physiological basis of HRV. Relevant linear and nonlinear HRV measures are explained and examples of their use in livestock stress research are provided. Finally, a rationale for the studies conducted in this dissertation is presented.</p><p>Chapter 2 evaluates the use of HRV as an indicator of castration pain in 9-d-old piglets over a 3-d experimental period. Compared to sham castrated piglets, surgically castrated piglets exhibited greater low frequency to high frequency ratios (<b>LF/HF</b>), reduced sample entropy (<b>SampEn</b>), and greater percent determinism (<b>ÞT</b>) during the post-castration period. However, postural behavior was not different between treatments and serum cortisol concentrations only tended to differ between treatments at 1 and 24 h post-castration treatment, with surgically castrated pigs having numerically greater serum cortisol concentrations at both timepoints. These results demonstrate the ability of nonlinear HRV measures (SampEn and ÞT) to complement the physiological interpretation of linear HRV measures (LF/HF) in response to castration. Specifically, pigs who were surgically castrated exhibited more regularity (SampEn) and periodicity (ÞT) in their HRV data, and potentially more sympathetic activity (LF/HF) compared to sham castrated piglets, indicating greater pain-related stress. Additionally, HRV was a more sensitive measure of the stress response to castration than readily identifiable behaviors such as posture and the serum cortisol response.</p><p>Chapter 3 evaluates the use of HRV as an indicator of disbudding pain in dairy heifer calves (4 to 7-wk of age) over a 5-d experimental period. Calves who were given lidocaine and meloxicam prior to disbudding exhibited lower mean R-R interval (<b>RR</b>) values and a greater short-term detrended fluctuation analysis scaling exponent (<b>DFAα₁</b>) than sham disbudded calves. Together, these results indicate that calves who received pain mitigation exhibited greater pain-related stress (RR) and reduced physiological complexity in their heart rate signal (DFAα₁). Calves who were disbudded without pain mitigation had an intermediate response compared to sham disbudded calves and calves provided lidocaine and meloxicam. However, their numerical values closely followed those of calves provided lidocaine and meloxicam. These results demonstrate the usefulness of nonlinear HRV measures (DFAα₁) for evaluating nonlinear and correlational aspects of physiological complexity in response to disbudding. Additionally, the HRV results suggest that the provision of meloxicam does not reduce the amount of pain-related stress experienced by calves following disbudding.</p><p>Chapter 4 evaluates the use of HRV as an indicator of heat stress in growing pigs exposed to an acute heat episode. Heat stressed pigs exhibited greater body temperatures and spent less time in an active position compared to thermoneutral control pigs. Additionally, heat stressed pigs displayed an altered nonlinear HRV response to the acute heat phase compared to non-heat stressed control pigs. Specifically, heat stressed pigs exhibited lower SampEn and tended to exhibit greater ÞT, but no alterations to linear measures were observed in response to the acute heat episode. The low frequency to high frequency ratio was higher in heat stressed pigs during the period following the acute heat phase. Therefore, nonlinear HRV measures (particularly SampEn) may be more sensitive to the immediate physiological stress response to increased environmental temperature than traditional linear HRV measures.</p><p>Chapter 5 evaluates the use of baseline HRV as a potential indicator of the subsequent cortisol and pro-inflammatory cytokine response to an LPS challenge in growing pigs. The time for a pig to approach a human (<b>approach time)</b> prior to LPS administration was inversely related to baseline standard deviation of the R-R intervals (<b>SDNN</b>), and directly related to RR and the mean length of diagonal lines in a recurrence plot (<b>Lmean</b>). This result may have implications for the use of HRV as a measure of temperament in livestock species, since pigs with lower baseline SDNN (<i>i.e.</i> greater stress) and greater baseline Lmean (<i>i.e.</i> increased periodicity length in HRV data; greater stress) values took longer to approach a human observer before LPS administration (which occurred 1 d after HRV measurement). Area under the curve values for approach time following LPS administration were inversely related to high frequency spectral power (<b>HF</b>) and directly related to body weight, where pigs with low baseline HF values (<i>i.e. </i>lower parasympathetic activity) and higher body weights were slower to approach a human observer following LPS administration. Additionally, pigs with greater Lmean values had a greater change in body temperature following LPS administration. In conclusion, while baseline HRV measures were not directly representative of the cortisol or cytokine response following an LPS challenge, HF and Lmean may be useful indicators for evaluating certain aspects (sickness behavior and fever) of the innate immune response to an LPS challenge. <b></b></p><p> In conclusion, these studies demonstrate the usefulness of nonlinear HRV measures for evaluating livestock stress. Measures such as sample entropy and those derived from recurrence quantification analysis (ÞT, Lmean) seem to be particularly useful for complementing traditional linear HRV measures and, in some cases, are more sensitive measures of the physiological stress response (see chapter 4). Therefore, their inclusion in future studies on livestock HRV is warranted. However, further work is needed to fully elucidate the physiological significance of nonlinear HRV measures and their response to stress.</p>

Slow and deep breathing (SDB) has long been regarded as a nonpharmacological method for dealing with several physiological and emotional imbalances, and widely used for relaxation purposes. There is, however, limited understanding of the putative mechanisms by which SDB acutely impacts the cardiovascular and autonomic systems to elicit chronic adaptations. The present thesis explored how the manipulation of breathing pattern and intrathoracic pressure during SDB could further the understanding of the regulatory mechanisms that underpin the acute cardiovascular response to SDB. This thesis makes an original contribution to the existing knowledge by reporting a previously undescribed inversion of normal within-breath (inspiration vs. expiration) left ventricular stroke volume (LVSV) pattern for breathing frequencies < 8 breaths∙min-1. This finding might reflect the influence of a lag between enhanced right atrial filling and right ventricular stroke volume during inspiration, and its expression in left ventricular stroke volume; this lag results from the time required for blood to transit the pulmonary circulation. Furthermore, blood pressure variability (BPV) was reduced significantly at the lowest breathing frequencies, likely due to the involvement of baroreflex mediated responses. The pattern of responses was consistent with the buffering of respiratory-driven fluctuations in left ventricular cardiac output (Q̇) and arterial blood pressure (ABP) by within breath fluctuations in heart rate (fc), i.e., respiratory sinus arrhythmia (RSA) (Chapter 4). Chapter 5 demonstrated that magnifying negative intrathoracic pressure with inspiratory loading during SDB increased inspiratory pressure-driven fluctuations in LVSV and fc, and enhanced Q̇, independently of changes in VT and fR. The data support an important contribution to the amplification of RSA, during SDB, of previously underappreciated reflex, and/or 'myogenic', cardiac response mechanisms. The findings in Chapter 6 confirmed that inspiratory loading during SDB amplified the effects observed with un-loaded SDB (reported in chapter 5). In contrast, expiratory loading increased ABP and attenuated RSA, LVSV and Q̇ during SDB. A lower RSA for higher ABP, supports the presence of a formerly underappreciated contribution of sinoatrial node stretch to RSA, and throws into question the clinical benefits of expiratory resisted SDB, particularly in hypertensive populations. In conclusion, the findings of the present thesis provide novel information regarding the mechanisms contributing to acute cardiovascular response to SDB. These new insights may contribute to the development of more effective SDB interventions, geared towards maximising the perturbation to the cardiovascular control systems.

A obesidade é considerada atualmente um dos maiores problemas de saúde em humanos, sendo considerada endêmica entre adultos e crianças. Situação semelhante tem sido observada em medicina veterinária, como conseqüência de um desequilibrio energético que muitas vezes é resultado do tipo de manejo que os animais recebem. É caracterizada pelo acúmulo excessivo de gordura, superando 15% do peso ideal e culmina com várias modificações nas funções orgânicas. Em humanos, sabe-se que o excesso de peso gera alterações na hemodinâmica, no metabolismo, no estado inflamatório, gerando um aumento do volume circulatório, ativação do sistema nervoso simpático e hipertrofia ventricular e levando ao remodelamento cardíaco. As arritmias cardíacas têm sido descritas em indivíduos obesos, geralmente acompanhadas da hipertrofia ventricular esquerda ou da síndrome da apnéia do sono. A disfunção autonômica, avaliada pela redução da variabilidade da freqüência cardíaca, também é observada nos humanos obesos. Não foram encontradas arritmias em estudo com cães obesos no ECG de rotina. O Holter permite um registro contínuo da atividade elétrica cardíaca, enquanto o paciente continua com as suas atividades diárias normais, assim uma das suas principais indicações é a identificação de presença de arritmias que não são detectados pelo eletrocardiograma de curta duração. Desta forma, o objetivo do estudo foi avaliar, pelo método Holter, a presença de arritmias e, pela análise da variabilidade da freqüência cardíaca, avaliar o balanço autonômico em cães obesos. Para isto, foram selecionados 67 cães obesos com escore de condição corporal (ECC) 8 e 9 e 65 cães com peso ideal (ECC=5), pareados por raça/porte, gênero e idade. Os cães obesos não apresentaram alteração no eletrocardiograma de rotina e nem na mensuração da pressão arterial em relação ao grupo controle. No entanto, o grupo obeso, apresentou maior número de extrassístoles ventriculares, discreta hipertrofia de ventrículo esquerdo. Também foram observados menores valores nos parâmetros de variabilidade da freqüência cardíaca, indicando assim, uma disfunção autonômica. / Obesity is currently one of the major health problems in humans, and it is considered endemic among adults and children. A similar situation has been found in veterinary medicine, as a consequence of energy imbalance, resulting, most of the times from the management of these animals. It is characterized by excessive accumulation of fat, over 15% of ideal body weight, and culminates with various organic function modifications. In humans, it is known that body weight excess generates changes on hemodynamics, metabolism, inflammatory status, leading to increased circulatory volume, sympathetic nervous system activation, ventricular hypertrophy and leads to cardiac remodeling. Arrhythmias have been described in obese people, generally accompanied by ventricular hypertrophy or sleep apnea. The autonomic dysfunction, assessed by a decrease in heart rate variability, is also observed in humans. Arrhythmias were not observed in a previous study of routine ECG in obese dogs. Holter monitoring allows for the continuous registration of the electrical activity of the heart, while the patient continues the normal daily activities. Therefore, one of the main indications is the identification of the presence of arrhythmias that are not detected by the short duration ECG. The purpose of this study was to assess, by Holter method, the presence of cardiac arrhythmias, and by heart rate variability, to evaluate the autonomic balance in obese dogs. Sixty seven dogs, with a body condition score (BCS) of 8 and 9, and 65 dogs with ideal body (BCS= 5) weight were selected, matched for breed/size, gender and age. The obese dogs did not present changes on the routine ECG and blood pressure measurement, in relation to control group. Despite that, the obese group showed greater number of ventricular extra-systoles and mild left ventricular hypertrophy. There were also lower values of heart rate variability parameters, which indicate an autonomic dysfunction.

O organismo está sujeito a diversos estímulos estressantes que afetam processos fisiológicos. Embora as alterações de pressão arterial e frequência cardíaca sejam comuns frente à exposição ao estresse, elas podem variar de acordo com os diferentes estressores, tipo de estresse, duração, frequência e intensidade do estímulo aversivo utilizado. O estresse é capaz de alterar em animais a regulação autonômica e reflexos respiratórios, como a atividade do barorreflexo, quimiorreflexo e variabilidade da frequência cardíaca. Além disso, o estresse também é capaz de alterar o comportamento, que são melhorados com o uso de antidepressivos, como a fluoxetina. Nesse sentido, o presente estudo teve como objetivo avaliar se o mesmo tipo de estressor (homotípico) ou diferentes estressores (heterotípico) modulam as respostas cardiovasculares e respiratórias ativadas pelo barorreflexo e quimiorreflexo, respectivamente, além da variabilidade da frequência cardíaca. Além disso, verificar se o tratamento com crônico ou agudo com fluoxetina é capaz de prevenir as alterações ocasionas pelo estresse crônico. Para isto, foram utilizados ratos Wistar, pesando entre 350 a 500g que foram submetidos ao estresse crônico repetido (ECR, homotípico) ou estresse crônico variado (ECV, heterotípico) durante 14 dias consecutivos. Sete dias antes do início dos protocolos de estresse crônico foi iniciado o tratamento com fluoxetina agudo, onde os animais só receberam fluoxetina no dia do experimento ou crônico, em que os animais receberam fluoxetina todos os dias até o dia do experimento, completando 21 dias de tratamento. Os animais ECR e ECV apresentaram uma menor preferência por sacarose, demonstrando comportamento de anedonia, que foi prevenida com o tratamento crônico com fluoxetina. Adicionalmente, ambos os protocolos de estresse demonstraram uma tendência ao aumento nos níveis de corticosterona basais, no entanto os resultados não foram significativos. Ambos os grupos de estresse crônico também apresentaram uma diminuição no peso corporal, entretanto os animais do grupo controle e ECR tratados cronicamente com fluoxetina apresentaram uma diminuição pronunciada do peso corporal quando comparados com seus controles. O ECR aumentou os componentes taquicárdico e bradicárdico do barorreflexo, adicionalmente, o tratamento crônico com fluoxetina preveniu o aumento dos componentes simpático e parassimpático do barorreflexo, porém induziu a redução desses componentes no grupo controle. O tratamento agudo com fluoxetina diminuiu apenas o componente bradicárdico de todos os grupos estressados e controle. Ambos os protocolos de estresse crônico promoveram uma diminuição na modulação simpato-vagal e no ganho do barorreflexo espontâneo, indicando uma hiperatividade simpática, que foi reduzida pelo tratamento crônico e agudo com fluoxetina. Entretanto o tratamento agudo aumentou o número de sequências barorreflexas do tipo UP (aumentos sucessivos de pressão arterial). O ECR e ECV também atenuaram a magnitude da resposta pressora frente à ativação do quimiorreflexo, que foi prevenida com ambos os tratamentos com fluoxetina. Os protocolos de estresse diminuíram os parâmetros basais de ventilação minuto (VE), volume corrente (VT) e aumentou a frequência respiratória (fR), além de aumentar a magnitude da frequência respiratória frente (?fR) a ativação do quimiorreflexo. No mesmo sentido, os tratamentos com fluoxetina aumentaram a magnitude da ?fR, porém apenas o tratamento crônico com fluoxetina preveniu as alterações no parâmetros basais respiratórios de VT e fR. Os achados do presente estudo demonstram que o estresse crônico provoca comportamento do tipo depressivo, além de alterar as respostas autonômicas de barorreflexo e quimiorreflexo e variabilidade cardiocirculatória (PAS e IP), o que pode desencadear patologias no sistema cardiovascular e respiratório. Adicionalmente, nosso trabalho é um dos primeiros a demonstrar que o tratamento crônico com fluoxetina previne a maioria das alterações ocasionadas pelo estresse crônico frente a essas alterações autonômicas / The body is submitted to various stressful stimuli that may affect many physiological processes. Although blood pressure and heart rate oscilations are common during exposure to stress, they can vary according to the different stressors type, duration, frequency and intensity of the aversive stimulus. Several studies suggest that stress can alter the autonomic regulation and respiratory reflexes, such as the baroreflex, chemoreflex activities and heart rate variability. In addition to cardiovascular disorders, chronic stress can also induce behavioral changes that are similar to depression in humans and are reversed by antidepressants, such as fluoxetine. In this way, the present study aimed to assess whether the same type of stressor (homotypic) or different stressors (heterotypic) are able to alter cardiovascular and respiratory responses activated by baroreflex and chemoreflex, respectively. We also aimed to verify the heart rate variability and if the chronic treatment with fluoxetine is able to prevent occasional alterations by chronic stress. For this purpose, male Wistar rats were used, weighing between 350 -500g. They underwent repeated chronic stress (RCS, homotypic) or unpredictable chronic stress (UCS, heterotypic) for 14 consecutive days. Seven days before starting the stress protocols was started the chronic or acute treatment with fluoxetine, until the day of the experiment, completing 21 days of treatment. The RCS and UCS animals have a lower preference for sucrose, demonstrating anhedonia behavior, which was prevented by chronic treatment with fluoxetine. Additionally, both stress protocols showed a tendency to increase basal levels of corticosterone, but the results were not significant. Our results showed that both stress groups have a decrease in body weight, however the control animals and RCS chronically treated with fluoxetine showed a marked decrease in body weight compared to their controls. The RCS increased tachycardia and bradycardia baroreflex components, however chronic treatment with fluoxetine prevented the increase of the sympathetic and parasympathetic components of the baroreflex, but induced a reduction of these components in the control group. Acute treatment with fluoxetine only decreased bradycardic component of all stressed and control groups. Both chronic stress protocols showed a decrease in sympathovagal modulation and spontaneous baroreflex gain, indicating a sympathetic hyperactivity that was decreased by chronic and acute treatment with fluoxetine. Acute fluoxetine treatment increased baroreflexs sequences up. The RCS and UCS also attenuated the magnitude of pressor response, which was prevented by both treatments with fluoxetine. Stress protocols decreased the baseline parameters of VE, VT and increased fR, and increase the magnitude of the respiratory frequency (?fR) by chemoreflex activation. Both treatment with fluoxetine further increased the magnitude of ?fR, but only chronic treatment with fluoxetine prevented the alterations in respiratory baseline parameters VT and fR. The findings of this study demonstrate that chronic stress causes the depressive-like behavior, and change the autonomic responses of baroreflex and chemoreflex and cardiocirculatory variability (PAS and IP), which can trigger diseases in the cardiovascular and respiratory system. In addition, our work is one of the first to show that chronic treatment with fluoxetine prevents most of the changes caused by chronic stress face these autonomic changes

O organismo está sujeito a diversos estímulos estressantes que afetam processos fisiológicos. Embora as alterações de pressão arterial e frequência cardíaca sejam comuns frente à exposição ao estresse, elas podem variar de acordo com os diferentes estressores, tipo de estresse, duração, frequência e intensidade do estímulo aversivo utilizado. O estresse é capaz de alterar em animais a regulação autonômica e reflexos respiratórios, como a atividade do barorreflexo, quimiorreflexo e variabilidade da frequência cardíaca. Além disso, o estresse também é capaz de alterar o comportamento, que são melhorados com o uso de antidepressivos, como a fluoxetina. Nesse sentido, o presente estudo teve como objetivo avaliar se o mesmo tipo de estressor (homotípico) ou diferentes estressores (heterotípico) modulam as respostas cardiovasculares e respiratórias ativadas pelo barorreflexo e quimiorreflexo, respectivamente, além da variabilidade da frequência cardíaca. Além disso, verificar se o tratamento com crônico ou agudo com fluoxetina é capaz de prevenir as alterações ocasionas pelo estresse crônico. Para isto, foram utilizados ratos Wistar, pesando entre 350 a 500g que foram submetidos ao estresse crônico repetido (ECR, homotípico) ou estresse crônico variado (ECV, heterotípico) durante 14 dias consecutivos. Sete dias antes do início dos protocolos de estresse crônico foi iniciado o tratamento com fluoxetina agudo, onde os animais só receberam fluoxetina no dia do experimento ou crônico, em que os animais receberam fluoxetina todos os dias até o dia do experimento, completando 21 dias de tratamento. Os animais ECR e ECV apresentaram uma menor preferência por sacarose, demonstrando comportamento de anedonia, que foi prevenida com o tratamento crônico com fluoxetina. Adicionalmente, ambos os protocolos de estresse demonstraram uma tendência ao aumento nos níveis de corticosterona basais, no entanto os resultados não foram significativos. Ambos os grupos de estresse crônico também apresentaram uma diminuição no peso corporal, entretanto os animais do grupo controle e ECR tratados cronicamente com fluoxetina apresentaram uma diminuição pronunciada do peso corporal quando comparados com seus controles. O ECR aumentou os componentes taquicárdico e bradicárdico do barorreflexo, adicionalmente, o tratamento crônico com fluoxetina preveniu o aumento dos componentes simpático e parassimpático do barorreflexo, porém induziu a redução desses componentes no grupo controle. O tratamento agudo com fluoxetina diminuiu apenas o componente bradicárdico de todos os grupos estressados e controle. Ambos os protocolos de estresse crônico promoveram uma diminuição na modulação simpato-vagal e no ganho do barorreflexo espontâneo, indicando uma hiperatividade simpática, que foi reduzida pelo tratamento crônico e agudo com fluoxetina. Entretanto o tratamento agudo aumentou o número de sequências barorreflexas do tipo UP (aumentos sucessivos de pressão arterial). O ECR e ECV também atenuaram a magnitude da resposta pressora frente à ativação do quimiorreflexo, que foi prevenida com ambos os tratamentos com fluoxetina. Os protocolos de estresse diminuíram os parâmetros basais de ventilação minuto (VE), volume corrente (VT) e aumentou a frequência respiratória (fR), além de aumentar a magnitude da frequência respiratória frente (?fR) a ativação do quimiorreflexo. No mesmo sentido, os tratamentos com fluoxetina aumentaram a magnitude da ?fR, porém apenas o tratamento crônico com fluoxetina preveniu as alterações no parâmetros basais respiratórios de VT e fR. Os achados do presente estudo demonstram que o estresse crônico provoca comportamento do tipo depressivo, além de alterar as respostas autonômicas de barorreflexo e quimiorreflexo e variabilidade cardiocirculatória (PAS e IP), o que pode desencadear patologias no sistema cardiovascular e respiratório. Adicionalmente, nosso trabalho é um dos primeiros a demonstrar que o tratamento crônico com fluoxetina previne a maioria das alterações ocasionadas pelo estresse crônico frente a essas alterações autonômicas / The body is submitted to various stressful stimuli that may affect many physiological processes. Although blood pressure and heart rate oscilations are common during exposure to stress, they can vary according to the different stressors type, duration, frequency and intensity of the aversive stimulus. Several studies suggest that stress can alter the autonomic regulation and respiratory reflexes, such as the baroreflex, chemoreflex activities and heart rate variability. In addition to cardiovascular disorders, chronic stress can also induce behavioral changes that are similar to depression in humans and are reversed by antidepressants, such as fluoxetine. In this way, the present study aimed to assess whether the same type of stressor (homotypic) or different stressors (heterotypic) are able to alter cardiovascular and respiratory responses activated by baroreflex and chemoreflex, respectively. We also aimed to verify the heart rate variability and if the chronic treatment with fluoxetine is able to prevent occasional alterations by chronic stress. For this purpose, male Wistar rats were used, weighing between 350 -500g. They underwent repeated chronic stress (RCS, homotypic) or unpredictable chronic stress (UCS, heterotypic) for 14 consecutive days. Seven days before starting the stress protocols was started the chronic or acute treatment with fluoxetine, until the day of the experiment, completing 21 days of treatment. The RCS and UCS animals have a lower preference for sucrose, demonstrating anhedonia behavior, which was prevented by chronic treatment with fluoxetine. Additionally, both stress protocols showed a tendency to increase basal levels of corticosterone, but the results were not significant. Our results showed that both stress groups have a decrease in body weight, however the control animals and RCS chronically treated with fluoxetine showed a marked decrease in body weight compared to their controls. The RCS increased tachycardia and bradycardia baroreflex components, however chronic treatment with fluoxetine prevented the increase of the sympathetic and parasympathetic components of the baroreflex, but induced a reduction of these components in the control group. Acute treatment with fluoxetine only decreased bradycardic component of all stressed and control groups. Both chronic stress protocols showed a decrease in sympathovagal modulation and spontaneous baroreflex gain, indicating a sympathetic hyperactivity that was decreased by chronic and acute treatment with fluoxetine. Acute fluoxetine treatment increased baroreflexs sequences up. The RCS and UCS also attenuated the magnitude of pressor response, which was prevented by both treatments with fluoxetine. Stress protocols decreased the baseline parameters of VE, VT and increased fR, and increase the magnitude of the respiratory frequency (?fR) by chemoreflex activation. Both treatment with fluoxetine further increased the magnitude of ?fR, but only chronic treatment with fluoxetine prevented the alterations in respiratory baseline parameters VT and fR. The findings of this study demonstrate that chronic stress causes the depressive-like behavior, and change the autonomic responses of baroreflex and chemoreflex and cardiocirculatory variability (PAS and IP), which can trigger diseases in the cardiovascular and respiratory system. In addition, our work is one of the first to show that chronic treatment with fluoxetine prevents most of the changes caused by chronic stress face these autonomic changes

This research compares methods for measuring pilot mental workload (MWL) from the electrocardiogram (ECG) signal. ECG-based metrics have been used extensively in MWL research. Heart rate (HR) and heart-rate variability (HRV) exhibit changes in response to varying levels of task demand. Classical methods for HRV analysis examine the ECG signal in the linear time and frequency domains. More contemporary research has advanced the notion that nonlinear elements contribute to cardiac control and ECG signal generation, spawning development of analytical techniques borrowed from the domain of nonlinear dynamics (NLD). Applications of nonlinear HRV analysis are substantial in clinical diagnosis settings; however, such applications are less frequent in MWL research, especially in the aviation domain. Specifically, the relative utility of linear and non-linear HRV analysis methods has not been fully assessed in pilot MWL research. This thesis contributes to aforementioned research gap by comparing a non-linear HRV method, utilizing transition probability variances (TPV), to classical time and frequency domain methods, focusing the analysis on sensitivity and diagnosticity. ECG data is harvested from a recent study characterizing spatial disorientation (SDO) risk amongst three candidate off-boresight (OBS) helmet-mounted display (HMD) symbologies in a tactically relevant live-flight task. A comparative analysis of methods on this dataset and supplemental workload analysis for the HMD study are presented. Results indicate the TPV method may exhibit higher sensitivity and diagnosticity than classical methods. However, limitations of this analysis warrant further investigation into this question.

Anxiety Sensitivity (AS), the belief that anxiety-related sensations may have harmful implications, can alter autonomic nervous system (ANS) function. Exercise has previously been shown to reduce AS; however, the effects of an exercise intervention on heart rate variability (HRV), a measure of ANS function, has not been evaluated in individuals with high AS. This study sought to 1) compare resting HRV in individuals with either low (LAS) or high AS (HAS) and 2) evaluate the effects of a 2-week exercise intervention on HRV and AS. Using the Anxiety Sensitivity Index (ASI-3), participants were identified as LAS (n=9; ASI-3=5.89±1.39) or HAS (n=15; ASI-3=32.87±2.49) and subsequently completed six 20-minute moderate intensity exercise sessions. HRV and psychosocial measures were obtained at baseline and following the 2-week intervention. No significant differences (p>0.05) in time or frequency domain HRV values between groups were revealed at baseline; however, when considering the HAS group alone, strong associations were observed between the ASI-3 score and HRV values in the time domain: RMSSD (r=-0.56), SDNN (r=-0.61), and pNN50 (r=-0.53). Following the intervention, changes observed in HRV and the higher and lower order (subscale) ASI-3 scores were not different between the groups; however, a medium to large effect was observed for the higher order ASI-3 and the cognitive subscale score, suggesting that our findings were likely limited by the small sample size. Further research is warranted to evaluate the relationship between HRV and AS and should seek to determine the most effective exercise interoceptive exposure for improving AS symptomology.

The impact of colour and lighting conditions on the emotions and performance of people is gaining greater importance in our urban societies. While large resources are allocated for well designed spaces with the right choices of colour and lighting conditions, there is little scientific evidence that supports these choices. Although the literature on light and colour is extensive, it does not present a uniform set of findings for a consistent perspective on the influence of colour and light. Most of the research reported in this field uses subjective measures to study the emotional effects of light and colour on people. It has been reported in literature that emotion manifests itself in three separate sections; (i) physiological (i.e. objective measures), (ii) psychological (subjective measures), (iii) behavioral, and it is necessary that studies not be limited to the assessment of a single response but include sample measures from each of the three manifestations. This research is built on the current body of knowledge that there is a need for a study on the emotional effects of light and colour on people using physiological and psychological measures, to ensure the objectivity and reproductivity of the experiments. It is well documented in literature that there is close correlation between emotions, heart rate (HR), and skin conductance (SC). Hence HR and SC are expected to be good physiological measures of environmental conditions on people. Thus this thesis reports changes in the HR, SC and self-assessment reports of arousal and valence (SAM) for people when exposed to different colour and intensity lights. The aim is to help provide an objective rationale for the choice for light intensity and colour by architects, interior designers and other professionals. The experiments were conducted on 15 participants who were exposed to 8 different colour and intensity light conditions. The participants' HR and SC were recorded under each colour and intensity light, and they were asked to complete SAM. The research demonstrates that there is a change in HR, SC, arousal and valence of participants due to change in the colour and intensity of lights. However, the direction of change was subject dependent, where the same colour and intensity light can have different effects on people. The research suggests that architects and designers of any space must take into account the individual differences of the predicted users when designing the lights and colours. It is also seen from the results that some colour and intensity lights have greater impact on the emotions of participants than others. Although it is not possible to correlate the colour and lighting conditions to a specific effect on all participants, general effects for some colour lights were drawn from the results. It is well documented in literature that HR and SC are a good measure of emotion. However the results of this study show very high inter subject variation in HR and SC. This is due to people having different HR and SC in normal conditions. This research demonstrates that the use of HR and SC to measure the effect of a stimulus on a group of people is unreliable because it is hard to compare the results.

Generalised polyneuropathy (PNP) is a common cause to neurological impairment, and may be an early symptom of a severe systemic disease. One such illness is hereditary transthyretin (TTR) amyloidosis (ATTR), a progressive fatal disorder caused by a mutation on the TTR gene. More than 100 such mutations have been found worldwide, of which Val30Met is the most common neuropathic variant with initial clinical manifestations indicating small fiber impairment. Differences in onset age, penetrance and phenotypes are present between endemic areas. Liver transplantation generally slows the progress of the symptom development, especially in patients with short disease duration. Ongoing research has also shown promising results with drug interventions. In any event, early diagnosis of PNP onset in ATTR patients is crucial to ensure early therapeutic interventions. Nerve conduction studies (NCS) and electromyography (EMG) provide the basis for evaluation of the functional state of the thick myelinated nerve fibres in patients with symptoms of PNP, but no such quantitative methods are available for the thin myelinated or unmyelinated fibers. Instead, a psychophysical method with thermal quantitative sensory testing (QST) can provide indirect information about the overall function in the afferent small fiber systems. The purpose of thesis was to evaluate the applicability of QST by the Method-of-limits (MLI) for early detection of PNP in Swedish ATTR patients with the Val30Met mutation. In healthy subjects the repeatability of the MLI was assessed, and reference values for thermal perception thresholds (TPT) in several body regions were determined. No significant differences in TPT or pain thresholds were found at repeated testing with MLI, indicating that the MLI is a reliable method. However, the results show that the arrangement of the testing order is of importance, as cold (CT) and warm (WT) perception thresholds were significantly elevated when tested after thermal pain assessments, instead of before. I general, the TPT was more elevated at lower parts of the body compared to the upper part, and with higher WT than CT, fully in accordance with the underlying anatomical and physiological prerequisites for QST. In biopsy verified ATTR patients lacking EMG and NCS abnormalities, significantly elevated TPT were found compared to controls. Furthermore, significantly more increased TPT were observed in patients with an early onset of the disease, compared those with a late onset. Finally, a combined detailed evaluation of QST and heart rate variability (HRV) analyses demonstrated correlations between QST and HRV abnormalities in patients with late onset, but not in those with early onset. The present thesis emphasizes the importance of incorporating QST early in the clinical evaluation of ATTR patients with a Val30Met mutation and with symptoms of thin fiber PNP. This is particularly indicated when patients report symptoms, or show signs, of neuropathic small fiber affection, but simultaneously exhibit normal EMG and NCS findings. The results furthermore underline the importance of performing both QST and HRV for a complete evaluation of both the thin somatic and autonomic nerve fibers, as both types of nerves may be affected early in the ATTR disease.

This thesis aims to increase the knowledge on people with symptoms attributed to electromagnetic fields (EMF) by investigating the effects of EMF exposure and by additional description of the heterogeneous group of people reporting EMF-related symptoms. The effect of mobile phone (MP)-like radio frequency (RF) fields on symptoms, autonomic nervous system (ANS) parameters, short-term memory, and reaction time in persons with MP-related symptoms (MP participants) was investigated in a provocation study. A second provocation study investigated the effect of similar exposure on serum concentration of biomarkers in persons with atopic dermatitis. No effect of exposure was detected in either study. MP participants displayed changes in heart rate variability (HRV) during cognitive tests, but not during rest. This contrasts with earlier findings, participants with symptoms attributed to EMF sources in general (EHS participants) displayed an elevated sympathetic nervous system activity both during cognitive tests and during rest. Proposed differences between subgroups of persons with EMF-related symptoms with respect to symptoms, personality traits and stress were investigated in a questionnaire study. MP participants reported primarily symptoms from the head; EHS participants reported symptoms from many organ systems. Furthermore, EHS participants reported higher levels of anxiety, depression, stress, and exhaustion when compared with a reference group. MP participants reported higher levels of anxiety and exhaustion only. In a pilot study, 24-hour and short-term HRV were investigated in EHS participants, to examine whether the previously observed sympathovagal imbalance would still be present. There was a tendency toward increased parasympathetic activity compared with earlier recordings, and a reduction of symptoms. Twenty-four hour and short-term recordings were fairly similar for each participant; however, there were large between-subject differences. The results do not support the hypothesis of effects of MP-like RF exposure on symptoms, ANS activity, CFFT, cognitive function, or biomarkers. However, they do support the hypothesis that persons with different symptom attribution (MP and EHS) may differ also in ANS activity and psychological aspects.