Background: In the past 37 years, increased efforts have been directed toward a better understanding of the importance of Hcy in disease and it has now become clear that hyperhomocysteinemia is a major independent risk factor for CVD. Extensive research on the influence of vitamin supplementation leading to reductions in Hcy levels and improvements in cardiovascular function has been done. The importance of exercise in the lowering of cardiovascular risk factors, as well as its favourable influence on cardiovascular function has also been indicated in several studies, however, the limited number of studies investigating the effect of exercise on Hcy concentrations revealed contradicting results. Furthermore, a relationship between Hcy concentration and cardiovascular function with the intervention of an exercise training and a vitamin supplementation programme respectively has also not been investigated. Objective: The objective of this study was to examine the effect of a 12-week exercise training and a 12-week vitamin supplementation intervention respectively on tHcy concentrations and cardiovascular function, and whether the change in tHcy concentration within the different interventions correlated with the change in cardiovascular function. Methods: In a randomised controlled cross-over intervention study, 52 men matched for age, cardiorespiratory fitness levels and cardiovascular risk factors were randomly assigned to one of 3 groups (Group A = exercise training programme, 20-30min. at 70-80% of HRmax; Group B = 400 g folic acid and 25 g vitamin B12 supplement; Group C = control). Group A and B were crossed over for phase 11, and Group C remained the control. The questionnaires were completed, and the body composition variables (BMI, WHR and body fat percentage), cardiovascular function (Finometer), tHcy concentrations and VO2max, were measured before and after each 12-week intervention period. A 6-week washout period separated the crossovers. Results: The ANCOVA, adjusted for age and BMI, showed that the percentage change from baseline to end, corrected for baseline of the tHcy concentration increased significantly (p ≤ .05) by 9.7% with the exercise training intervention and decreased significantly (p ≤ .05) by 12.9%, with the vitamin supplementation intervention. The ANCOVA of the percentage change from baseline to end in cardiovascular function showed that the vitamin supplementation intervention resulted in improvements in cardiovascular function (decreased resting MAP, TPR and increased resting SV, CO, Cw) in comparison to the impairment in cardiovascular function with the exercise training intervention (increased resting DBP, MAP and TPR). The relationship between the tHcy concentration and cardiovascular function at baseline and within each of the different interventions were assessed by partial correlations adjusted for age, BMI and VO2max. Significant (p ≤ .05) relationships only occurred within the vitamin supplementation intervention, where decreased percentage change in tHcy concentration significantly correlated with increased percentage change of resting SV and CO and decreased percentage change of resting TPR. Conclusion: The general conclusion that can be drawn is that a 12-week vitamin supplementation intervention showed increased health related results, e.g. a significant reduction in tHcy concentration, an improvement in cardiovascular function and a significant positive relationship between these b o factors, in comparison to the 12-week exercise training intervention that significantly increased the tHcy concentration and did not show increased health related results. Due to inadequate compliance to the exercise training intervention, no conclusion can be drawn with regard to the effect of exercise training on tHcy concentrations and cardiovascular function. / Thesis (M.Sc. (Human Movement Science))--North-West University, Potchefstroom Campus, 2007

Thesis (M.Sc. (Human Movement Science))--North-West University, Potchefstroom Campus, 2007.

Background: In the past 37 years, increased efforts have been directed toward a better understanding of the importance of Hcy in disease and it has now become clear that hyperhomocysteinemia is a major independent risk factor for CVD. Extensive research on the influence of vitamin supplementation leading to reductions in Hcy levels and improvements in cardiovascular function has been done. The importance of exercise in the lowering of cardiovascular risk factors, as well as its favourable influence on cardiovascular function has also been indicated in several studies, however, the limited number of studies investigating the effect of exercise on Hcy concentrations revealed contradicting results. Furthermore, a relationship between Hcy concentration and cardiovascular function with the intervention of an exercise training and a vitamin supplementation programme respectively has also not been investigated. Objective: The objective of this study was to examine the effect of a 12-week exercise training and a 12-week vitamin supplementation intervention respectively on tHcy concentrations and cardiovascular function, and whether the change in tHcy concentration within the different interventions correlated with the change in cardiovascular function. Methods: In a randomised controlled cross-over intervention study, 52 men matched for age, cardiorespiratory fitness levels and cardiovascular risk factors were randomly assigned to one of 3 groups (Group A = exercise training programme, 20-30min. at 70-80% of HRmax; Group B = 400 g folic acid and 25 g vitamin B12 supplement; Group C = control). Group A and B were crossed over for phase 11, and Group C remained the control. The questionnaires were completed, and the body composition variables (BMI, WHR and body fat percentage), cardiovascular function (Finometer), tHcy concentrations and VO2max, were measured before and after each 12-week intervention period. A 6-week washout period separated the crossovers. Results: The ANCOVA, adjusted for age and BMI, showed that the percentage change from baseline to end, corrected for baseline of the tHcy concentration increased significantly (p ≤ .05) by 9.7% with the exercise training intervention and decreased significantly (p ≤ .05) by 12.9%, with the vitamin supplementation intervention. The ANCOVA of the percentage change from baseline to end in cardiovascular function showed that the vitamin supplementation intervention resulted in improvements in cardiovascular function (decreased resting MAP, TPR and increased resting SV, CO, Cw) in comparison to the impairment in cardiovascular function with the exercise training intervention (increased resting DBP, MAP and TPR). The relationship between the tHcy concentration and cardiovascular function at baseline and within each of the different interventions were assessed by partial correlations adjusted for age, BMI and VO2max. Significant (p ≤ .05) relationships only occurred within the vitamin supplementation intervention, where decreased percentage change in tHcy concentration significantly correlated with increased percentage change of resting SV and CO and decreased percentage change of resting TPR. Conclusion: The general conclusion that can be drawn is that a 12-week vitamin supplementation intervention showed increased health related results, e.g. a significant reduction in tHcy concentration, an improvement in cardiovascular function and a significant positive relationship between these b o factors, in comparison to the 12-week exercise training intervention that significantly increased the tHcy concentration and did not show increased health related results. Due to inadequate compliance to the exercise training intervention, no conclusion can be drawn with regard to the effect of exercise training on tHcy concentrations and cardiovascular function. / Thesis (M.Sc. (Human Movement Science))--North-West University, Potchefstroom Campus, 2007

This thesis is concerned with the neurocircuitry that underpins the cardiovascular response to exercise, which has thus far remained incompletely understood. Small animal studies have provided clues, but with the advent of functional neurosurgery, it has now been made possible to translate these findings to humans. Chapter One reviews the background to the studies in this thesis. Our current understanding of the cardiovascular response to exercise is considered, followed by a discussion on the anatomy and function of various brain nuclei. In particular, the rationale for targeting the periaqueductal grey (PAG) and the subthalamic nucleus (STN) is reviewed. Chapter Two reviews the use of deep brain stimulation (DBS), in which deep brain stimulating electrodes are implanted into various brain nuclei in humans, in order to treat chronic pain and movement disorders. This technique not only permits direct electrical stimulation of the human brain, but also gives the opportunity to record the neural activity from different brain regions during a variety of cardiovascular experiments. This chapter also gives a detailed methodological description of the experimental techniques performed in the studies in this thesis. Chapter Three identifies the cardiovascular neurocircuitry involved in the exercise pressor reflex in humans using functional neurosurgery. It shows for the first time in humans that the exercise pressor reflex is associated with significantly increased neural activity in the dorsal PAG. The other sites investigated, which had previously been identified as cardiovascular active in both animals and humans, seem not to have a role in the integration of this reflex. Chapter Four investigates whether changes in exercise intensity affect the neurocircuitry involved in the exercise pressor reflex. It demonstrates that the neural activity in the PAG is graded to increases in exercise intensity and corresponding increases in arterial blood pressure. This chapter also provides evidence to suggest that neural activity in the STN corresponds to the cardiovascular changes evoked by the remote ischaemic preconditioning stimulus in humans. Chapter Five identifies the cardiovascular neurocircuitry involved during changes in central command during isometric exercise at constant muscle tension using muscle vibration. It shows that, in humans, central command is associated with significantly decreased neural activity in the STN. Furthermore, the STN is graded to the perception of the exercise task, i.e. the degree of central command. The other sites investigated appear not to have as significant a role in the integration of central command during the light exercise task that was undertaken. Chapter Six studies the changes in muscle sympathetic nerve activity (MSNA) during stimulation of various brain nuclei in humans. Regrettably, the results presented in this chapter are not convincing enough to support the hypothesis that stimulation of particular subcortical structures corresponds to changes in MSNA. However, the cardiovascular changes that were recorded during stimulation of the different subcortical structures are congruous with previous studies in both animals and humans. Chapter Seven presents a brief summary of the findings in this thesis.

L’hypoxie désigne une baisse de la biodisponibilité en oxygène au niveau tissulaire. La combinaison de l’hypoxie intermittente et de l’hypercapnie est identifiée dans le cadre de plusieurs maladies respiratoires comme un élément physiopathologique déterminant. Cependant, des travaux de recherche suggèrent qu’une exposition à l’hypoxie hypo- ou normocapnique à l’éveil peut améliorer la santé cardiovasculaire. La combinaison d’une exposition hypoxique et de l’entraînement à l’effort est utilisée par les athlètes pour améliorer la performance sportive aérobie. Des études pilotes récentes y compris chez le malade chronique indiquent que l’exposition à l’hypoxie modérée au repos ou à l’effort chez le patient est susceptible d’induire des gains significatifs en termes de santé cardiovasculaire, de composition corporelle et de statut métabolique.Nous nous sommes intéressés aux effets cardiorespiratoires et tissulaires de l’exposition hypoxique normobarique chez le sujet sain et chez la personne en surpoids ou obèse présentant un risque ou des anomalies cardio-métaboliques. Nous avons étudié l’efficacité de 2 types de conditionnement au repos consistant en une hypoxie continue ou une hypoxie intermittente et un entraînement à l’effort hypoxique par comparaison à la situation normoxique. Nous avons tout d’abord étudié les effets d’une exposition hypoxique à court terme au repos chez 14 sujets sains. Nous avons ensuite étudié les effets cardiorespiratoires, tissulaires, vasculaires et métaboliques d’un programme de conditionnement hypoxique normobarique à moyen terme au repos chez 35 patients en surpoids ou obèse. Nous avons de plus réalisé chez 24 sujets sains une étude préliminaire afin de vérifier la faisabilité et de caractériser les réponses cardio-respiratoires et l’oxygénation tissulaire au cours d’un exercice aigu à charge constante d’intensité modérée ou intermittent intense en hypoxie comparé à une condition placébo normoxique. La dernière étude a consisté à étudier les conséquences cardiorespiratoires, tissulaires, vasculaires et métaboliques d’un programme d’entraînement à l’effort en hypoxie par rapport au même programme en normoxie chez 23 patients en surpoids ou obèses.L’étude réalisée chez le sujet sain met en évidence l’intérêt à court terme d’un conditionnement hypoxique intermittent au repos sur des variables associées aux risques cardiovasculaires (diminution de la pression artérielle systolique en normoxie et augmentation de la variabilité sinusale) et une modulation de l’hypoxie tissulaire. Nous avons montré chez le sujet sain que l’hypoxie combiné à l’exercice aigu provoque une diminution de l’oxygénation musculaire similaire mais une diminution de l’oxygénation du cortex préfrontal plus importante par comparaison à un effort normoxique à même intensité relative. Ensuite, chez le sujet en surpoids ou obèse, nous avons montré que le conditionnement hypoxique passif chronique induit une diminution de la pression artérielle diastolique de repos en normoxie, une augmentation de la réponse ventilatoire hypoxique et une diminution de la variabilité cardiaque (après conditionnement par hypoxie intermittente seulement) et que le conditionnement hypoxique actif chronique améliore l’aptitude maximale aérobie par rapport à une situation placébo normoxique.Les résultats obtenus montrent la faisabilité de plusieurs conditionnements hypoxiques prometteurs au plan vasculaire y compris chez le sujet en surpoids ou obèse limité à l’exercice musculaire. Le conditionnement hypoxique actif montre également des bénéfices accrus sur l’aptitude aérobie. Ces protocoles de conditionnement doivent être affinés en vue d’optimiser leur efficacité en termes de perte de poids et d’amélioration du risque cardio-vasculaire et métabolique dans des populations présentant une obésité associée à une morbidité cardio-métabolique. Ils représentent également une piste thérapeutique innovante dans d’autres pathologies chroniques / Hypoxia refers to a decrease in the oxygen bioavailability at the tissue level. The combination of intermittent hypoxia and hypercapnia is identified in several respiratory diseases as a critical pathophysiological element. However, research suggests that exposure to hypo- or normocapnic hypoxia can improve cardiovascular health. The combination of hypoxic exposure and exercise training has been used by athletes to improve aerobic exercise performance. Recent pilot studies in patients with chronic diseases indicate that exposure to moderate hypoxia at rest or during exercise is likely to induce significant gains in cardiovascular health, body composition and metabolic status.We investigated the effects of normobaric hypoxic exposure on cardiorespiratory and tissue function in healthy subjects, overweight or obese subjects at risk or with cardio-metabolic abnormalities. We assessed the efficacy of 2 types of passive hypoxic conditioning consisting in sustained hypoxia or intermittent hypoxia and hypoxic exercise training in comparison with normoxic condition. First, we assessed the effects of short-term hypoxic exposure at rest in 14 healthy subjects. Then, we evaluated the cardiovascular and metabolic effects of a 8-week normobaric hypoxic conditioning program at rest (intermittent or sustained hypoxia) in 35 overweight or obese patients, compared to placebo normoxic exposure. Next, we conducted a preliminary study in 24 healthy subjects to assess the acute responses to submaximal constant-load and high intensity interval cycling exercise performed in normoxia and in hypoxia. The last study aimed to compare the effect of an 8-week exercise training program performed either in normoxia or hypoxia on maximal aerobic capacity in overweight or obese subjects.In the healthy subject, we emphasized the rapid benefits of intermittent hypoxic conditioning on cardiovascular function (lower baseline systolic blood pressure and increased heart rate variability) and the modulation of tissue deoxygenation in response to hypoxia. We have also shown in healthy subjects that acute exercise (combined with hypoxia causes a similar decrease in muscle oxygenation but a greater prefrontal cortex deoxygenation compared to normoxic condition. Then, in the overweight or obese subject, we have shown that chronic passive hypoxic conditioning induces a decrease in diastolic blood pressure at rest in normoxia, an increase in the hypoxic ventilatory response and a decrease in heart rate variability after intermittent hypoxic conditioning only. In addition, chronic active (exercise training) hypoxic conditioning improves the maximal aerobic capacity compared to placebo normoxic training.Our results show the feasibility of several hypoxic conditioning strategies and their interesting effects on the vascular function in overweight/obese subjects presenting exercise limitations impeding exercise reconditioning. In addition, active hypoxic conditioning showed a greater effect on physical fitness than normoxic exercise training. These hypoxic conditioning strategies must be further optimized to improve their efficacy regarding weight loss and cardiometabolic morbidity in obese. They also represent promising therapeutic opportunities for other chronic diseases

No description available.

Gestational hypothyroidism is a prevalent disorder in pregnant women. We aimed to investigate the impact of experimental gestational hypothyroidism (EGH) on cardiovascular and autonomic nervous systems (ANS) in the offspring of rats. EGH was induced with methimazole (MMI) 0.02% in drinking water from day 9 of gestation until birth. Sixty days old offspring from MMI-treated dams (OMTD, n=13) or water-treated dams (OWTD, n=13) had femoral arteries surgically assessed for the measurements of heart rate (HR), mean (MAP), systolic (SAP) and diastolic arterial pressure (DAP), and spontaneous baroreflex sensitivity (BRS). To investigate the balance of ANS, we established the high (HF) and low frequency (LF) bands of pulse interval (PI) and LF band of SAP spectrum. OMTD had increased MAP (130.2±2.0 vs 108.8±3.0 mmHg, p < 0.001), SAP (157.3±2.9 vs 135.7±4.5 mmHg, p < 0.001) and DAP (109.7±1.9 vs 88.4±2.6 mmHg, p < 0.001) when compared to OWTD, and had lower HR (355.1±8.9 vs 386.8±9.2 bpm, p < 0.05). After spectral analysis of PI and SAP, only LF band of SAP spectrum was higher (7.2±0.8 vs 4.0±0.6 mmHg2) in OMTD under spontaneous condition. Despite bradicardia, EGH promotes spontaneous hypertension in 60 days old offspring, probably due to increased sympathetic activity to vessels, which is suggested by the higher LF of SAP. These findings suggest a critical role of maternal THs in the development of fetal cardiovascular and autonomic nervous system. / Os hormônios da tireoide (HTs), tiroxina (T4) e triiodotironina (T3), são reconhecidos por influenciar o crescimento e metabolismo celulares em todo o organismo. Os HTs são fundamentais para o bom desenvolvimento embrionário. O hipotireoidismo é uma das doenças endócrinas mais frequentes, acometendo frequentemente mulheres gestantes, sobretudo na forma subclínica (HS). O suprimento de HTs para o feto em praticamente toda a gestação é de origem materna. A deficiência destes hormônios está implicada com desordens no neurodesenvolvimento fetal, assim como no desenvolvimento e diferenciação cardiovasculares. No presente estudo objetivamos investigar as repercussões do hipotireoidismo gestacional experimental (HGE) na função cardiovascular da prole quando adulta. O HGE foi induzido pela administração de metimazol (MMI), um inibidor da síntese de HTs, a 0,02%, p.o., em água de beber ad libitum, do 9º dia de gestação até o parto. A prole de mães hipotireoideas (PMH) foi acompanhada desde o nascimento (dia 0 pós-natal; 0 DPN) até 60º DPN), onde foram submetidos ao procedimento cirúrgico de canulação da artéria femoral para registro dos parâmetros cardiovasculares. Vinte e quatro horas após, foram registrados os seguintes parâmetros cardiovasculares: frequência cardíaca (FC), pressão arterial média (PAM), pressão sistólica (PS) e pressão diastólica (PD). Após coletados, os dados foram analisados para a obtenção do índice de sensibilidade do barorreflexo (SBR), dos componentes de baixa (LF) e de alta frequência (HF) da análise da variabilidade da frequência cardíaca (VFC). Foram obtidos ainda a razão LF/HF e variabilidade da PS, analisado pelo LF absoluto (LFabs). O grupo controle foi composto por prole de mães eutireoideas (PME). O peso corporal da prole foi registrado para verificação e comparação do desenvolvimento corporal de ambos os grupos. Os resultados obtidos demonstram um menor peso corporal na PMH a partir do 21 DPN perdurando até os 60 DPN (p<0,001). A PMH também apresentou FC reduzida, com aumento da PAM, PS e PD quando comparados a PME (p<0,05). Não foram observadas diferenças significativas entre os grupos na LF, HF, LF/HF. No entanto, o LFabs foi mais elevado na prole de mães induzidas ao HGE, (7,2±0,8 vs 4,0±0,6 mmHg2, p<0,01). Diante do exposto concluímos que o HGE afeta o desenvolmento corporal da prole, assim como altera o funcionamento do sistema cardiovascular, sem, aparentemente afetar o sistema nervoso autonômico de controle da função cardíaca. Contudo, apesar da bradicardia, o HGE promove hipertensão espontânea aos 60 DPN, provavelmente devido ao aumento da atividade simpática nos vasos, como demonstrado pelo alto LFabs.

Advancements in clinical care have led to a growing cohort of preterm-born individuals now entering adulthood. Before birth, such adults were often exposed to a suboptimal intrauterine environment, and after delivery, key developmental stages that would normally occur in utero during the third trimester had to take place under ex utero physiological conditions. Through detailed cardiovascular phenotyping, this thesis investigates the cardiovascular changes in preterm-born young adults, utilising a cohort of individuals with data collection since recruitment at birth. The detailed perinatal information was first used to design nested case-control studies to investigate the effects of early lipid and glucocorticoid exposure on long-term cardiovascular physiology in individuals born preterm. It was demonstrated that intravenous lipid administration leads to an artificial elevation of total cholesterol levels in immediate postnatal life, which is associated with long-term changes in aortic and left ventricular function proportional to the degree of cholesterol elevation. Additionally, exposure to antenatal glucocorticoids relates to a regional increase in aortic arch stiffness in young adulthood, as well as changes in glucose metabolism. It was then shown that young adults born preterm have increased left ventricular mass, out of proportion to blood pressure, and a unique three-dimensional left ventricular geometry, with reduced systolic and diastolic function compared to term-born controls. Similarly, they also show distinct differences in the right ventricle, with increased right ventricular mass and a proportion having clinically impaired right ventricular systolic function. Finally, it was demonstrated that preterm-born individuals have increased circulating levels of antiangiogenic factors in young adulthood, which relate to capillary rarefaction and blood pressure elevation. These findings are of considerable public health relevance given that nearly 10% of births are now preterm. Understanding whether modification of these variations in cardiovascular structure and function prevent the development of cardiovascular disease in this growing subgroup of the population will be of future interest.