Arterial wall morphology depends strongly on the hemodynamic environment experienced in vivo. The mammalian heart pumps blood through rhythmic contractions forcing blood vessels to undergo cyclic, mechanical stimulation in the form of pulsatile blood pressure and flow. While it has been shown that stepwise, chronic increases in blood pressure and flow modify arterial wall thickness and diameter respectively, few studies on arterial remodeling have examined the influences that pulsatility (i.e., the range of cyclic stimuli) may have on biaxial wall morphology. We experimentally studied the biaxial behavior of carotid arteries from 8 control (CCA), 15 transgenic, and 21 mechanically altered mice using a custom designed mechanical testing device and correlated those results with hemodynamic measurements using pulsed Doppler. In this dissertation, we establish that increased pulsatile stimulation in the right carotid artery after banding (RCCA-B) has a strong affect on wall morphological parameters that peak at 2 weeks and include thickness (CCA=24.8±0.878, RCCA-B=99.0±8.43 μ m), inner diameter (CCA=530±7.36, RCCA-B=680±32.0μ m), and in vivo axial stretch (CCA=1.7±0.029, RCCAB= 1.19±0.067). These modifications entail stress and the change in stress across the cardiac cycle from an arterial wall macro-structural point of view (i.e., cellular and extracellular matrix) citing increases in collagen mass fraction (CCA=0.223±0.056, RCCA-B=0.314±0.011), collagen to elastin ratio (CCA=0.708±0.152, RCCA-B=1.487±0.26), and cross-sectional cellular nuclei counts (CCA=298±58.9, RCCA-B=578±28.3 cells) at 0, 7, 10, 14, and 42 post-banding surgery. Furthermore, we study the biomechanical properties of carotid arteries from a transgenic mouse of Marfan Syndrome. This arterial disease experiences increased pulse transmission and our findings indicate that alterations occur primarily in the axial direction. The above results are all applied to a predictive biaxial model of Cauchy stress vs. strain.

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Background: Cardiovascular disease (CVD) is the leading cause of death worldwide. Well-established risk factors for CVD include increasing age, male sex, sedentary lifestyle, obesity, smoking, diabetes, hypertension, dyslipidaemia and low socio-economic status. Traditional risk factors do, however, not fully explain cardiovascular risk in general. In this thesis we focused on two conventional risk factors (smoking, blood pressure), and two unconventional risk markers (adiponectin, an adipocyte derived protein; and sialic acid (SA), a marker of systemic inflammation) for prediction of CVD events. Aims: In Paper I we examined to what degree smoking habits modify the risk of CVD in relation to systolic blood pressure levels in middle-aged men. In Paper II we investigated the predictive role of adiponectin for risk of CVD as well as the cross-sectional associations between adiponectin and markers of glucose metabolism, also in men. In Paper III we examined if increasing pulse pressure (PP) and increasing levels of SA both increase the risk of CVD and whether their effects act in synergism. In Paper IV the association of SA with risk of incident diabetes mellitus and related complications, resulting in hospitalization, was studied. Subjects and Methods: Two large-scale, population-based, screening studies with long follow-up periods have been used. The Malmö Preventive Project (MPP) was used with 22,444 individuals in Paper I and a sub cohort of 3,885 individuals in Paper II. The Värmland Health Survey (VHS) was used in Papers III and IV with 37,843 and 87,035 individuals, respectively. Results: CVD risk increases with increasing systolic blood pressure levels and this risk is almost doubled in smokers. Total adiponectin level is not associated with increased risk of future CVD but it is inversely associated with markers of glucose metabolism. PP and SA both contribute to risk of future CVD. Adjustment for mean arterial pressure reduces the risk induced by PP. Elevated SA contributes to increased risk of incident diabetes and related complications leading to hospitalization.

<p>The aim of this thesis is to develop and study a method for estimation of the pulse pressure in centrally located arteries. Obtaining the central pulse pressure is desirable for several reasons. For example, the central pulse pressure can be used to assess aortic stiffness, which in turn is an important predictor of cardiovascular mortality. In this thesis a method of estimation based on a one--dimensional wave propagation theory applied to a physiological model of the human systemic arterial tree is studied. For the purpose of validation, recorded pressure signals from twenty four control subjects are used. Various methods for individualization of the tree model are discussed, and a method that utilizes an optimization routine is proposed.</p>

The aim of this thesis is to develop and study a method for estimation of the pulse pressure in centrally located arteries. Obtaining the central pulse pressure is desirable for several reasons. For example, the central pulse pressure can be used to assess aortic stiffness, which in turn is an important predictor of cardiovascular mortality. In this thesis a method of estimation based on a one--dimensional wave propagation theory applied to a physiological model of the human systemic arterial tree is studied. For the purpose of validation, recorded pressure signals from twenty four control subjects are used. Various methods for individualization of the tree model are discussed, and a method that utilizes an optimization routine is proposed.

Research Objective Patients with chronic kidney disease (CKD) are at increased risk for atherosclerosis and peripheral artery disease (PAD). PAD has received far less attention than coronary artery disease (CAD) in CKD patients. Few studies have examined risk factors for PAD in CKD. We studied the possible related risk factors and benefit of hypertension treatment in CKD patients with PAD. Data Sources We included 129 patients of both sexes with stages 3 to 5 of CKD, as described by the Kidney Outcome Quality Initiatives (K/DOQI ) classification, without receiving dialysis therapy, not previously diagnosed with PAD. Study Design The following information were collected within six month period, including demographic characteristics, history of hypertension, anti-hypertension drug, diabetes, smoking, and pre-existing cardiovascular disease, body mass index (BMI), fasting blood glucose, HbA1c, total cholesterol, triglyceride(TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol(LDL), calcium (Ca), phosphate(P), Albumin, uric acid, urine protein. Ankle-brachial index (ABI) is a noninvasive diagnostic test that is efficient in detecting asymptomatic PAD with ABI <0.9. Findings There were 22 (17.7 %) participants with PAD. Higher systolic blood pressure (SBP), higher diastolic blood pressure (DBP), higher pulse pressure showed strong association with PAD in CKD patients. On further analysis, significant fewer patients treated with calcium channel blocker (CCB) in hypertensive CKD patients with PAD (£q2 =7.055, p =0.008). The multivariate logistic regression analysis in hypertensive patients demonstrated the risk factors for PAD was pulse pressure, and Calcium channel blocker treatment may correlate with decreasing PAD formation (odds ratio= 0.232, 95% CI=0.07-0.73, p =0.013) in CKD patients. Conclusion There is a high prevalence rate of PAD in population of CKD, especially those with hypertension. ABI should be routinely examined in these patients who can benefit earlier from therapeutic measures.

Motivation: Ischemic heart disease is the eighth leading cause of death in an African population. Silent ischemia can be defined as an ischemic episode without associated pain. The clinical significance of silent ischemia is growing and can now be considered as a risk factor in the development of coronary disease. Hypertension and associated risk factors, hypercholesterolemia and diabetes are associated with silent ischemia. Other factors such as higher pulse pressure, double product, heart rate and higher carotid intima-media thickness are also associated with silent ischemia. Urbanisation is rising in South-Africa. This new lifestyle is associated with several risk factors including: poor diets, lower physical activity levels, hypertension and increased smoking and alcohol abuse. The prevalence of stroke is high among Africans, which can be due to a higher prevalence of hypertension, diabetes and obesity. Purpose: The purpose of this study was to determine the associations between silent ischemia and cardiovascular function in African men. The focus fell on hypertension and associated risk factors, higher total cholesterol levels, and increased pulse pressure, heart rate and sub-clinical atherosclerosis. vi Methodology: This study constituted a population study in the North-West province carried out on urbanized African male teachers aged between 20-60 years. The SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) sub-study consisted of a total of 80 African male volunteers. The Cardiotens apparatus was placed on each participant on the first morning. This apparatus took ambulatory blood pressure measurements as well as Electrocardiogram measurements. Hereafter, participants continued with their normal work day until 1700. After an overnight stay at the Metabolic unit of the North-West University Potchefstroom campus, the apparatus was removed at 0600. During statistical analyses, the African males were divided into groups of participants with silent ischemia (SI) and those without silent ischemia (nSI), as determined by the ambulatory electrocardiogram. Statistical analyses were performed by means of the Statistica version 10 software program. Results: In comparison with the nSI men, the SI showed the following: above normal high sensitivity C-reactive protein and glucose, higher ambulatory blood pressure, heart rate, pulse pressure, resting ST-segment depression and carotid intima-media thickness. Multiple regression analyses indicated that ambulatory silent ischemia is associated with sub-clinical atherosclerosis, possibly increasing their stroke risk. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2012.

Motivation: Ischemic heart disease is the eighth leading cause of death in an African population. Silent ischemia can be defined as an ischemic episode without associated pain. The clinical significance of silent ischemia is growing and can now be considered as a risk factor in the development of coronary disease. Hypertension and associated risk factors, hypercholesterolemia and diabetes are associated with silent ischemia. Other factors such as higher pulse pressure, double product, heart rate and higher carotid intima-media thickness are also associated with silent ischemia. Urbanisation is rising in South-Africa. This new lifestyle is associated with several risk factors including: poor diets, lower physical activity levels, hypertension and increased smoking and alcohol abuse. The prevalence of stroke is high among Africans, which can be due to a higher prevalence of hypertension, diabetes and obesity. Purpose: The purpose of this study was to determine the associations between silent ischemia and cardiovascular function in African men. The focus fell on hypertension and associated risk factors, higher total cholesterol levels, and increased pulse pressure, heart rate and sub-clinical atherosclerosis. vi Methodology: This study constituted a population study in the North-West province carried out on urbanized African male teachers aged between 20-60 years. The SABPA (Sympathetic activity and Ambulatory Blood Pressure in Africans) sub-study consisted of a total of 80 African male volunteers. The Cardiotens apparatus was placed on each participant on the first morning. This apparatus took ambulatory blood pressure measurements as well as Electrocardiogram measurements. Hereafter, participants continued with their normal work day until 1700. After an overnight stay at the Metabolic unit of the North-West University Potchefstroom campus, the apparatus was removed at 0600. During statistical analyses, the African males were divided into groups of participants with silent ischemia (SI) and those without silent ischemia (nSI), as determined by the ambulatory electrocardiogram. Statistical analyses were performed by means of the Statistica version 10 software program. Results: In comparison with the nSI men, the SI showed the following: above normal high sensitivity C-reactive protein and glucose, higher ambulatory blood pressure, heart rate, pulse pressure, resting ST-segment depression and carotid intima-media thickness. Multiple regression analyses indicated that ambulatory silent ischemia is associated with sub-clinical atherosclerosis, possibly increasing their stroke risk. / Thesis (M.Sc. (Physiology))--North-West University, Potchefstroom Campus, 2012.

Le speckle laser est un effet d'interférence longtemps considéré comme néfaste lors de l'utilisation de sources de lumière cohérente. Cependant, pour certaines applications, cet effet peut être bénéfique et utilisé comme source d'information. C’est le cas du domaine biomédical.Ainsi, le speckle laser est utilisé depuis des décennies pour la surveillance du flux sanguin microvasculaire. Il commence à être considéré aussi pour l'extraction de paramètres de la macrocirculation sanguine. Ce travail vise donc tout d’abord à démontrer que le speckle laser permet d'évaluer les paramètres hémodynamiques de la macrocirculation avec fiabilité et à partir d’une technique identique à celle employée dans l’étude de la microcirculation. Ceci conduira à une intégration rapide du dispositif dans les instruments existants. Par ailleurs, l'un des problèmes les plus importants du speckle laser,empêchant l’obtention d’une analyse totalement quantitative, est l'effet des diffuseurs statiques. Ce type de diffuseurs influence fortement le contraste de speckle, conduisant à une mauvaise interprétation des données. Le second objectif de ce travail est donc d'étudier l'effet des diffuseurs statiques sur la corrélation et le contraste du speckle laser. Nos résultats montrent tout d’abord que le speckle laser est un phénomène intéressant pour extraire les paramètres hémodynamiques de la macrocirculation. Par ailleurs, nos études révèlent que le calcul de la corrélation du speckle laser permet d'estimer le rapport entre diffuseurs statiques / dynamiques avec une bonne fiabilité. En outre, le contraste temporel permet de déterminer les diffuseurs dynamiques possédant des vitesses différentes. / The laser speckle is an interference effect that has been considered as a main drawback in the use of coherent light sources. However, for a specific set of applications, this effect can become a source of information. Among these applications there are the biomedical ones. The laser speckle has been used for decades to monitor microvascular blood flow but only now starts to be considered as a method that can also be used for macrocirculation parameters extraction. This work first aims at demonstrating that laser speckle can be used for macrocirculation assessment with good reliability, using the same technique as the one employed in microcirculation assessment. The use of the same methods could lead to a rapid inclusion of this new evaluation in the existing devices. Furthermore, one of the most important laser speckle issues, that prevents a fully quantitative analysis, is the effect of static scatterers. This type of scatterers strongly influences the speckle contrast, leading to a wrong interpretation of the data. The second objective of this work is to study the effect of statics catterers on the laser speckle correlation and contrast. Our results show that the laser speckle is an interesting phenomenon to extract hemodynamic parameters in the macrocirculation. This work also demonstrates that the laser speckle correlation is able to estimate the ratio between static/dynamic scatterers with good reliability. Moreover, the temporal speckle contrast achieved a very good performance in discerning dynamic scatterers with different velocities.

Ao contrário dos indicadores estáticos, como a pressão venosa central e a pressão de oclusão da artéria pulmonar, a variação da pressão de pulso arterial tem se mostrado um indicador hemodinâmico preciso para a determinação da responsividade à administração de fluido. Objetivo: Este estudo objetivou mensurar a variação da pressão de pulso em cadelas mecanicamente ventiladas submetidas a expansão volêmica durante procedimento cirúrgico eletivo (ovário-salpingo-histerectomia) e determinar a relação deste indicador com os dados hemodinâmicos obtidos por meio do exame ecodopplercardiográfico transesofágico. Material e método: Quinze cadelas foram distribuídas aleatoriamente em dois grupos: sem pressão positiva ao final da expiração (GI - ZEEP, n = 7) e com pressão positiva ao final da expiração de 5cmH2O (GII - PEEP, n = 8). As avaliações hemodinâmicas incluindo freqüência cardíaca (FC), pressão arterial média invasiva (PaM), variação da pressão de pulso (VPP), pressão venosa central (PVC), volume sistólico (VE), índice cardíaco (IC), velocidade do fluxo aórtico (VFA) e gradiente de pressão do fluxo aórtico (Grad); análise de gases sangüíneos e parâmetros do sistema respiratório incluindo freqüência respiratória (FR) e pressão de pico inspiratória (PIP), foram mensuradas antes da aplicação da PEEP em cadelas do GII (M0); imediatamente antes (M1) e cinco minutos após (M2) a expansão volêmica com 10ml/Kg de solução de Ringer Lactato. Os grupos e tempos foram comparados por meio da análise de variância (ANOVA) seguida do teste de Tukey, com nível de significância de 5%. Resultados: A utilização da PEEP ocasionou um significante aumento dos seguintes parâmetros: VPP (M0 - 9.5 ± 2.92 vs M1 - 12.1 ± 2.19, P < 0.05); PVC ( 4.9 ± 2.47 vs 6.5 ± 2.73, P < 0.05); PIP (9.9 ± 1.36 vs 13.0 ± 2.2, P < 0.05) e PaO2 (336.5 ± 64.04 vs 373.6 ± 97.82, P < 0.05). Os animais do GI apresentaram um significante aumento dos seguintes parâmetros depois da expansão volêmica: VE (25.4 ± 3.92 vs 19.1 ± 3.22, P < 0.05), IC (3.8 ± 0.99 vs 2.4 ± 0.47, P < 0.05), VFA (93.8 ± 17.60 vs 74.5 ± 14.66, P < 0.05) e Grad (3.6 ± 1.30 vs 2.3 ± 0.92, P < 0.05). Alterações significativas também foram observadas nos seguintes parâmetros do GII depois da expansão volêmica: PaM (108.6 ± 20.6 vs 96.9 ± 19.97, P < 0.05), VPP (5.2 ± 1.8 vs 12.1 ± 2.19, P < 0.05), VE (26.6 ± 8.18 vs 20 ± 5.15, P < 0.05), IC (3.6 ± 0.90 vs 2.4 ± 0.56, P < 0.05), VFA (97.6 ± 25.49 vs 83.6 ± 24.12, P < 0.05) e Grad (4.0 ± 2.01 vs 3.0 ± 1.64, P < 0.05). Quando comparado M1 do GI e do GII, diferença significativa foi observada com a VPP (7.1 ± 1.64 vs 12.1 ± 2.19, P < 0.05). A FR foi maior no GII quando comparada ao GI (FR GII M1 e GII M2 - 16.9 ± 1.36 vs GI M1 - 14.9 ± 1.35 e GI M2 - 15.3 ± 1.5, P < 0.05). PIP foi também maior no GII quando comparada ao GI (GII M1 - 13.0 ± 2.20 vs GI M1 - 7.3 ± 2.21; GII M2 - 13.4 ± 2.50 vs GI M2 - 7.7 ± 2.14, P < 0.05). Conclusão: Este estudo mostrou que a variação da pressão de pulso é um índice adequado para avaliar o estado hemodinâmico durante a instituição de PEEP, sendo a avaliação ecodopplercardiográfica transesofágica uma excelente técnica de monitoração do estado hemodinâmico nos pacientes submetidos a procedimento cirúrgico. / Contrary to static parameters such as central venous pressure and pulmonary capillary wedge pressure, pulse pressure variation has proven itself as an accurate hemodynamic tool for the determination of fluid responsiveness. Objective: To measure pulse pressure variation in mechanically-ventilated bitches submitted to volume load during elective surgery (ovariohysterectomy) and to determine its relationship with hemodynamic parameters obtained with transesophageal Doppler echocardiography. Material and Methods: Fifteen bitches were randomly distributed between two groups: with zero end-expiratory pressure (GI - ZEEP, n=7) and with positive end-expiratory pressure of 5cmH2O (GII - PEEP, n=8). Hemodynamic evaluations including heart rate (HR), invasive mean arterial pressure (MAP), pulse pressure variation (PPV), central venous pressure (CVP), stroke volume (SV), cardiac index (CI), aortic blood flow velocity and aortic flow pressure gradient; blood-gas analysis and ventilatory parameters including respiratory rate (RR) and peak inspiratory pressure (PIP), were measured before employment of PEEP in bitches from GII (M0); immediately before (M1) and five minutes after (M2) volume expansion using 10ml/Kg lacted Ringers solution. Statistical analysis was based on ANOVA for repeated measures followed by Turkeys t-test with significance level of 0.05. Results: The use of PEEP induced a significant increase in the following parameters: PPV (M0 - 9.5 ± 2.92 vs M1 - 12.1 ± 2.19, P < 0.05); CVP ( 4.9 ± 2.47 vs 6.5 ± 2.73, P < 0.05); PIP (9.9 ± 1.36 vs 13.0 ± 2.2, P < 0.05) and PaO2 (336.5 ± 64.04 vs 373.6 ± 97.82, P < 0.05). Animals in GI presented a significant increase in the following parameters after fluid load: SV (25.4 ± 3.92 vs 19.1 ± 3.22, P < 0.05), CI (3.8 ± 0.99 vs 2.4 ± 0.47, P < 0.05), aortic blood flow velocity (93.8 ± 17.60 vs 74.5 ± 14.66, P < 0.05) and aortic flow pressure gradient (3.6 ± 1.30 vs 2.3 ± 0.92, P < 0.05). Statistical significance of the following parameters were observed in GII after fluid load: MAP (108.6 ± 20.6 vs 96.9 ± 19.97, P < 0.05), PPV (5.2 ± 1.8 vs 12.1 ± 2.19, P < 0.05), SV (26.6 ± 8.18 vs 20 ± 5.15, P < 0.05), CI (3.6 ± 0.90 vs 2.4 ± 0.56, P < 0.05), aortic blood flow velocity (97.6 ± 25.49 vs 83.6 ± 24.12, P < 0.05) and aortic flow pressure gradient (4.0 ± 2.01 vs 3.0 ± 1.64, P < 0.05). When comparing M1 of GI and GII, a statistical significant difference was observed with PPV (7.1 ± 1.64 vs 12.1 ± 2.19, P < 0.05). Respiratory rate was greater in GII than in GI (RR GII M1 and GII M2 - 16.9 ± 1.36 vs GI M1 - 14.9 ± 1.35 and GI M2 - 15.3 ± 1.5, P < 0.05). Peak inspiratory pressure was also greater in GII than in GI (GII M1 - 13.0 ± 2.20 vs GI M1 - 7.3 ± 2.21; GII M2 - 13.4 ± 2.50 vs GI M2 - 7.7 ± 2.14, P < 0.05). Conclusion: This study showed that the pulse pressure variation is an adequate indicator to evaluate the hemodynamic status during PEEP application, being the transesophageal Doppler echocardiography evaluation a great tool in monitoring the hemodynamic status in patients undergoing surgery.