Dissertations / Theses on the topic 'Arterial pressure. eng'

Orientador: Araildo Lima da Silva
Banca: Carlos Renato Zacharias
Banca: Clifford Neves Pinto
Resumo: O presente trabalho consiste no estudo do comportamento do fluxo sangüíneo na artéria braquial, através de sinais captados por um microfone acoplado no estetoscópio e utilizado para transformar o sinal acústico (sonoro) em elétrico, e enviá-lo para o computador. O estudo foi realizado oferecendo-se diferentes pressões no esfigmomanômetro, o qual foi adaptado com dois manômetros. Um dos manômetros, graduado em mmHg, não foi modificado, possui o selo do INMETRO e atuou como referência, ao outro foi inserido um extensômetro, que transformou o sinal de pressão em sinal elétrico, utilizando uma ponte amplificada, enviando-o para uma placa de aquisição de dados no computador. Foi traçada uma curva de calibração do sinal elétrico (em mV) com relação ao manômetro graduado em mmHg. Foi proposto um protocolo para aquisição destes sinais a serem analisados, baseado em protocolos de aferição de pressão arterial. O comportamento do fluxo sangüíneo foi comparado às diferentes pressões exercidas pelo esfigmomanômetro. Ao analisar estes dados, foram propostos limites de normalidades da intensidade do sinal do fluxo sangüíneo em diferentes freqüências nas cinco fases da escala de Koroktov. O trabalho mostrou também os limites de normalidade da pressão arterial, utilizando-se o sinal adquirido pela extensometria. Finalmente, foi oferecido mais um auxílio no diagnóstico de patologias do sistema cardiovascular.
Abstract: The present work consists to study the features of blood flow in to the brachial artery through signals detected by a microphone coupled together a stethoscope. This apparatus changes the acoustics in eletric signal and, then, sends to the computer. This study was implemented exhibiting different pressures in the sphygnomanometer, where two manometers, graded in mmHg, were coulpled. One that has the INMETRO certificate of gauging instruments was not modificate and, then, it was used as the standard. In the other, an extensometer was coupled together, which through an amplifier bridge, pressure signals are transformed in electric signals and sent to a data adapter unit connected to the computer. A gauging curve for the eletric signals versus pressure signals was ploted. It was proposed a protocol to adquire these data signals, based on the protocol of brachial pressure measurement. The features of blood flow were compared at different sphygnomanometer pressures. In the analysis process of the data, normality boundaries of intensity were proposed to the blood flow signal at different frequencies in the five phases of the Koroktov scale. The work also showed the normality boundaries of brachial pressure using the data signals adquired by the extensometry process. Finally, it was provided an one more aid in to diagnose pathologies in the cardiovascular system.
Mestre

Orientador: Newton Nunes
Banca: Paulo Sérgio Patto dos Santos
Banca: Celina Tie Nishimori Duque
Resumo: Para avaliar os efeitos da infusão contínua de naloxona ou tramadol sobre a resposta à hipovolemia aguda foram utilizados 40 coelhos adultos distribuídos em cinco grupos: grupo naloxona (GN), grupo tramadol 1 (GT1), grupo tramadol 3 (GT3), grupo tramadol 5 (GT5) e grupo controle (GC). Os animais foram induzidos (2,5 CAM) e mantidos (1,5 CAM) à anestesia com isofluorano e após 60 minutos receberam bolus de solução de NaCl a 0,9% (GC), de naloxona (GN) ou de diferentes doses de tramadol (GT1, GT3 e GT5), seguido de infusão contínua dos mesmos fármacos. Decorridos dez minutos, os coelhos foram induzidos à hipovolemia por meio da retirada de sangue arterial no volume total de 15 ml/kg, o qual foi reinfundido após uma hora. Os parâmetros avaliados foram frequência cardíaca, eletrocardiografia, pressão venosa central, pressões arteriais (PA), pressão de perfusão coronariana (PPC), frequência respiratória, saturação de oxiemoglobina e tensão parcial de dióxido de carbono ao final da expiração. Os dados foram submetidos à análise de variância seguida pelo teste de Tukey (p<0,05). Houve diminuição significativa das médias de PA e PPC após a retirada sanguínea, em todos os grupos, com posterior retorno aos valores iniciais durante a reinfusão do sangue, com exceção do GT5 que apresentou médias estáveis durante a hipovolemia e reinfusão. O GC e GT1 apresentaram médias de PA e PPC menores que as do GT5 vinte minutos após a remoção sanguínea. As demais variáveis não apresentaram diferença significativa ao longo do período experimental. Concluiu-se que a administração do tramadol, na dose de 5 mg/kg seguida por infusão contínua de 0,025 mg/kg/min, é indicada na terapia da hipovolemia aguda, pois possui ações benéficas na PA e na PPC, sem alterar os demais parâmetros estudados.
Abstract: To evaluate the effects of continuous infusion of naloxone or tramadol on the answer to acute hypovolemia, forty adult rabbits were assigned into five groups: naloxone group (NG), tramadol group 1 (TG1), tramadol group 3 (TG3), tramadol group 5 (TG5) and control group (CG). General anesthesia was induced (2.5 CAM) and maintained (1.5 CAM) with isoflurane and, after sixty minutes, the bolus of NaCl to 0.9% (CG), of naloxone (NG) or the several doses of tramadol (TG1, TG3 e TG5) followed by continuous infusion of the same drugs were administered. After 10 minutes, the rabbits were induced to hypovolemia by withdrawing arterial blood in total volume of 15 ml/kg, which was reinfused after one hour. Heart rate, electrocardiogram, venous central pressure, arterial pressures (AP), coronary perfusion pressure (CPP), respiratory rate, pulse oxygen saturation and end-tidal carbon dioxide were evaluated. Numerical data were submitted to analyses of variance followed by Tukey test (p<0.05). The AP and CPP decreased significantly, after blood withdrawal, in all groups. During blood reinfusion, these parameters came back to the initial values, except in TG5, because these variables were stable during hypovolemia and blood reinfusion. The CG and TG1 showed mean of AP and CPP lower than the TG5 at twenty minutes after the withdrawal of blood. It was concluded that tramadol administration, at dose of 5 mg/kg followed by continuous infusion of 0.025 mg/kg/min, is indicated in therapy of acute hypovolemia, because it has useful action on AP and on CPP, besides this drug does not impair the other evaluated parameters.
Mestre

Orientador: Aparecido Antonio Camacho
Banca: Aulus Cavalieri Carciofi
Banca: Glaucia Bueno Pereira Neto
Banca: José Alberto Montoya Alonso
Banca: Julio Carlos Canola
Resumo: O estudo caracterizou a influência da obesidade e do sobrepeso sobre parâmetros cardiovasculares em gatos. Foram estudados 15 gatos obesos, sete com sobrepeso e sete com escore de condição corporal ideal. Não foram evidenciadas alterações laboratoriais compatíveis com estímulo do sistema renina angiotensina-aldosterona. Verificou-se a ocorrência pressão arterial sistólica acima de 150mmHg em 73,33% dos animais obesos, com nítido aumento (p < 0,0001) da PAS no grupo obeso, comparado aos grupos sobrepeso e com ECC ideal. O aumento da PAS foi acompanhado de disfunção diastólica, havendo correlação da PAS com a relação E/A do fluxo mitral (p = 0,0008, r = -0,40), além de maiores valores de espessura da parede livre e do septo interventricular na diástole (p<0,05). À avaliação radiográfica, não foram verificadas diferenças no VHS e distância precordial, apenas maiores valores da mensuração da gordura falciforme nos animais obesos. Com relação às anormalidades eletrocardiográficas, houve maior ocorrência de arritmias ventriculares complexas ao Holter de 24 horas dos gatos obesos (p<0,05). O ritmo predominante na eletrocardiografia computadorizada foi sinusal, enquanto no Holter de 24 horas, foi arritmia sinusal em todos os grupos. Não houve diferenças entre as frequências cardíacas entre os grupos, tampouco variação circadiana. Também não se observaram diferenças entre os períodos em bradicardia ou taquicardia e entre os índices de variabilidade da frequência cardíaca no domínio do tempo. Na avaliação respiratória, animais obesos anestesiados apresentaram menores volumes correntes e VCO2 (p<0,05) além da tendência à hipoxemia. Gatos em sobrepeso também apresentaram menores valores de PaO2, porém sem alterações na ventilometria ... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: This study aimed to characterize the influence of obesity and overweight on cardiovascular parameters in cats. Twenty nine cats were evaluated (15 obese, seven overweight and seven with ideal ECC). There were no differences on parameters that reflect increase of aldosterone-angiotensin renin activity in obese cats. Systolic blood pressure was higher than 150mmHg in 73.33% of obese animals with a marked increase in systolic blood pressure (p < 0,0001) in obese group, compared to overweight or cats with ideal ECC. The increase in systolic blood pressure was accompanied by diastolic dysfunction, evidenced by the correlation (p = 0.0008, r = -0.40) with the E/A ratio of mitral flow. Moreover, obese animals had higher values of free wall thickness and interventricular septum in diastole (p<0,05). At radiographic evaluation, there were no differences in VHS, precordial distance and chest depth, only higher values of falciform fat in the obese animals. Regarding electrocardiographic abnormalities, in 24-Holter of obese cats, it was found a higher occurrence of complexes ventricular arrhythmias. The predominant rhythm in computerized ECG was sinus rhythm, while in the 24-hour Holter was sinus arrhythmia in all groups. There was no difference between heart rate throughout the day, either between the groups. Also, there were no differences in the periods of bradycardia or tachycardia and in the indexes of heart rate variability in the time domain between groups. Regarding the respiratory evaluation, anesthetized obese cats showed lower tidal volumes and VCO2 (p<0,05) and obese and overweight cats showed a tendency to hypoxemia. Therefore, obesity can cause changes on cardiorespiratory parameters, proportionally to increase of body weight and body fat
Doutor

Orientador: Marileda Bonafim Carvalho
Banca: Mácia Mery Kogika
Banca: Sandra Regina Ribeiro da Silva
Banca: Mirela Tinucci Costa
Banca: Áureo Evangelista Santana
Resumo: A função renal está sob influência de diversos hormônios, entre eles podemos citar o sistema renina-angiotensina-aldosterona (SRAA), que possui importante papel na manutenção do volume circulante e equilíbrio eletrolítico, entretanto também está relacionado com a progressão da doença renal. Entre seus efeitos deletérios, pode-se citar a hipertensão arterial e glomerular, proteinúria e glomeruloesclerose. Em Medicina, o tratamento medicamentoso da doença renal crônica consiste na utilização de inibidores da enzima conversora da angiotensina (iECA), antagonistas dos receptores da angiotensina II (ATAII) e/ou antagonistas da aldosterona, na forma de bloqueios simples, duplo ou triplo. Entretanto, somente o primeiro grupo de medicamentos é utilizado em Medicina Veterinária. Para testar a hipótese, que os bloqueios duplos e triplos possam beneficiar animais portadores de DRC, o presente estudo teve como objetivo avaliar a função renal de cães sadios e nefropatas submetidos a protocolos diferentes de inibição do SRAA. Os animais foram submetidos a terapias isoladas ou combinadas com cloridrato de benazepril, losartan potássico e espironolactona, durante sete dias, sendo avaliados no último dia. As avaliações consistiam em bioquímica sérica, urinálise, U-P/C, Ccr, metabolismo do sódio e potássio, além da PAS. Nos cães sadios, as terapias com benazepril (isolado ou associado) induziram aumento da concentração sérica de potássio, enquanto os bloqueios, duplo e triplo, reduziram a PAS. Nos nefropatas, todas as terapias reduziram a proteinúria, enquanto as terapias associadas reduziram a PAS e a excreção renal de potássio
Abstract: The renal function is under several hormones, like reninangiotensin- aldosterone system (RAAS), that have an important hole in the control of extravascular volume and electrolytic balance, however is related in the progression of renal disease, with proteinuria, glomerular hyperfiltration and glomerulosclerosis. In Medicine, the medical treatment of chronic renal failure consists in the use of ACE inhibitors, angiotensin II receptors antagonists (AIIRA) and/or aldosterone antagonists, however, only the first group is used in Veterinary Medicine. To prove the hypothesis that double or triple blockade can benefits animals with CRD, this study was conducted to evaluate the renal function of healthy dogs under different protocols of inhibition of RAAS. The dog received isolated ou associated therapies with benazepril, losartan and espironolactone, for seven days, with evaluation on the seventh Day. The evaluations consisted in serum biochemistry, urinalisis, UPC, Ccr, sodium and potassium metabolism, and SAP. In the healthy dog, the therapy with benazepril (isolated or associated) increased serum potassium levels, while the blockaded, duple or triple, decreased SAP. In nephropatic dogs, all therapies decreased proteinuria, while associated therapies decreased SAP and renal excretion of potassium
Doutor

Orientador: Eduardo Kokubun
Banca: Cláudio Alexandre Gobatto
Banca: Eliete Luciano
Banca: Sandra Lia do Amaral
Banca: Ricardo Jacó de Almeida
Resumo: Uma alta incidência de hipertensão arterial, que possui uma etiologia multifatorial envolvendo fatores genéticos, ambientais e psicológicos, tem sido observada na população mundial. Desta forma o entendimento dos mecanismos celulares e moleculares envolvidos na gênese da hipertensão arterial é fundamental para se alcançar medidas preventivas e terapêuticas para o controle da pressão arterial. O óxido nítrico (NO) produzido pelas células endoteliais assume um importante papel no controle cardiovascular, pois tem sido considerado ser um potente vasodilatador e regulador da pressão arterial. Entretanto, as disfunções endoteliais, caracterizadas pela baixa produção e/ou biodisponibilidade do NO e alguns fatores genéticos (polimorfismos), podem contribuir para o surgimento da hipertensão arterial. Assim, o objetivo deste estudo foi investigar a influência de um programa de exercício aeróbio nas concentrações e biodisponibilidade de NO em portadores do polimorfismo T-786C do gene da eNOS e verificar o efeito dessas variáveis na pressão arterial. O DNA dos participantes foi isolado das células mononucleares periféricas e o diagnóstico genético foi realizado pela técnica de PCR. As análises de concentrações de NO, atividade da superóxido dismutase (SOD), pressão arterial, fluxo sanguíneo, composição corporal (índice de massa corporal e porcentagem de gordura corporal), perfil lipídico (colesterol total, LDL-colesterol, HDL-colesterol e triglicerídeos) e glicemia foram analisadas antes de após 6 meses de um programa de exercício físico aeróbio (70% do VO2 max) em adultos de meia idade e idosos subdivididos de acordo com a genotipagem o nível inicial de pressão arterial. Os resultados mostraram que as variáveis do perfil lipídico não exerceram nenhuma influência na relação entre hipertensão, concentrações de NO e polimorfismo do gene da eNOS... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Hypertension has a high incidence in the population of the world and its etiology is multifatorial, involving genetic, environmental and psychological factors. Understanding of the cell and molecular mechanisms involved in the genesis of hypertension is fundamental for the attainment of preventive and/or therapeutic measures for blood pressure control. Nitric Oxide (NO) produced by the endothelial cells has a particularly important role in cardiovascular control because it is a potent vasodilator and thus its role in blood pressure control is extremely relevant. However, the endothelial dysfunction which is characterized by a lower production and/or NO bioavailability, and some genetic factors can contribute to the genesis of hypertension. Therefore, the purpose of this study was investigate the influence of aerobic exercise training (AEX) on the NO concentration and bioavailability in 786C allele carriers and verify the effect of theses variable on the blood pressure. Genomic DNA was isolated from peripheral mononuclear cells and genotyping was done by standard PCR methods. The NOx assay, SOD activity, casual blood pressure, blood flow, body composition (body mass index and body fat), and lipid profile (cholesterol, LDL-cholesterol, HDLcholesterol, glucose, and triglycerides) was evaluated before and after 6 months of AEX (70% of VO2 max) in adults and elderly divided in groups according genotype and blood pressure levels. The results showed that there is no interference of lipid profile on the relationship among hypertension, NO concentration and eNOS polymorphism and the body composition variables showed a small interference on this relationship. NOx levels was associated with blood pressure values and NOx levels were significantly lower in the TC+CC group compared to the TT group at baseline... (Complete abstract click electronic access below)
Doutor

Orientador: Thais Borges César
Banca: Magali C. Monteiro da Silva
Banca: Lívia Gussoni Basile
Resumo: Este estudo teve como objetivo investigar a ingestão regular do suco de laranja de polpa vermelha sobre alguns fatores de risco para o desenvolvimento de doenças cardiovasculares em indivíduos adultos residentes nos municípios de Araraquara (SP) e Matão (SP). A variedade das laranjas de polpa vermelha é também conhecida como laranja sanguínea de Mombuca, e sua coloração é devida à presença de carotenóides, especialmente beta-caroteno e licopeno. Participaram deste estudo 19 homens e 16 mulheres que receberam 750 mL/dia de suco de laranja vermelha pasteurizado durante 8 semanas. As variáveis antropométricas utilizadas foram: peso, altura, dobras cutâneas do tríceps, bíceps, subescapular e suprailíaca e circunferência da cintura. Para a avaliação bioquímica foram realizadas dosagens de colesterol total, colesterol de HDL, apolipoproteínas A1 e B, proteína C reativa, homocisteína, triglicérides e glicemia. Para a avaliação hemodinâmica foram verificadas a pressão arterial sistólica e a diastólica, e para a avaliação dietética foi utilizado o recordatório alimentar de 24 horas. Todas as avaliações foram realizadas antes e após o consumo de suco de laranja vermelha. Os resultados mostraram que o colesterol total foi reduzido em 9% entre os participantes que consumiram o suco de laranja vermelha, o colesterol de LDL em 11%, a apolipoproteína B em 5% e a proteína C reativa em 49%. A pressão arterial sistólica foi reduzida em 4% entre os participantes eutróficos e a pressão diastólica foi reduzida em 4% entre os participantes com excesso de peso. Não houve diminuição significativa das variáveis antropométricas. O consumo do suco de laranja vermelha aumentou em 907% a ingestão de vitamina C e 145% a ingestão de folato das mulheres, e 1130% de vitamina C e 123% de folato dos homens. A ingestão regular de suco de laranja vermelha apresentou... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: This study had as objective investigates the regular ingestion of the red orange juice over risk factors for the development of cardiovascular disease in adults residents in the cities of Araraquara (SP) and Matão (SP). The variety of red pulp orange is also known as Mombuca blood orange, and its color is due to the carotenoids, especially from beta-carotene and lycopene. The study included 19 men and 16 women, which received 750 mL/d of pasteurized red orange juice during 8 weeks. It was evaluated in all subjects: weigh, height, skin folds (triceps, biceps, subscapular and suprailiac), waist circumference and systolic and diastolic blood pressure. Biochemical parameters were accomplished for total cholesterol, HDL cholesterol, apolipoproteins A1 and B, C reactive protein, homocysteine, triglycerides and glucose. For hemodynamic assessment were observed systolic and diastolic blood pressure and dietary evaluation was estimated using 24h food record. All evaluations were accomplished before and after consumption of red orange juice. The results showed that the consumers of red orange juice decreased total cholesterol by 9%, LDLcholesterol by 11%, apo B by 5% and the C reactive protein by 49%. Systolic blood pressure was reduced 4% among eutrophic participants and the diastolic blood pressure reduced 4% among the pre-obese participants. There was no significant reduction on anthropometric variables. Consumption of red orange juice increased 10 folds the intake of vitamin C and double the intake of folate for all volunteers. Regular consumption of red orange juice has shown hypolipidemic and hypotensive properties, while both juices, from the red and yellow oranges, have shown antiinflammatory effects
Mestre

Central pulse pressure (cPP), a product of ventricular-arterial interaction, is an important determinant of cardiovascular outcomes in hypertension. The aim of this thesis is to advance the understanding of pulsatile haemodynamics and to explore mechanisms that may selectively reduce cPP. The conventional view is that cPP comprises a component determined by the direct interaction of myocardial contraction with the impedance of the proximal arterial tree (closely related to pulse wave velocity, PWV) and a component ‘augmentation pressure’ generated by pressure wave reflections from muscular conduit arteries. Surprisingly little is known regarding regulation of conduit artery tone despite its potential influence on cPP. In the first part of this thesis, muscular large arterial tone was examined using a human forearm blood flow model. Vasoactive substances were infused locally into the brachial artery and vasodilator responses of the radial artery, as a muscular conduit artery, and forearm resistance microvasculature were examined. Nitric oxide donors, in particular, glyceryl trinitrate (GTN) were found to have the most selective action on conduit arteries compared to other vasodilators. In the second part of the thesis, I examined whether the action of GTN to reduce augmentation pressure could be accounted for by this selective dilation of muscular arteries. GTN was given systemically and by intra-coronary infusion in patients undergoing cardiac catheterisation. Invasive aortic blood pressure and flow velocity were analysed in the time domain by wave intensity analysis. This allows separation of pressure into a forward component generated by myocardial contraction and a backward component generated by ‘reflection’ from the peripheral arterial tree. A surprising finding was that changes induced by GTN were mainly attributable to a reduction in forward rather than backward pressure waves. That this resulted from a change in myocardial contractility was confirmed by local intracoronary injection of GTN. The final part of the thesis examines the relative contribution of forward and backward pressure waves in hypertension. An elevated cPP in hypertensive compared to normotensive subjects was accounted for primarily by an increased forward pressure wave. That this was due to increased myocardial contractility was confirmed by examining whether the pattern of wave intensity seen in hypertension could be reproduced, in normotensive subjects, by the inotrope dobutamine (when compared to the vasoconstrictor norepinephrine used as a control). This thesis thus provides novel insight into a) regulation of conduit artery tone, and b) pulsatile haemodynamics, highlighting the contribution of left ventricular ejection characteristics in determining pressure augmentation and cPP.

Objectives: To assess the prevalence of left ventricular hypertrophy (LVH) inpatients with newly diagnosed peripheral arterial disease (PAD). Methods: Consecutive patients referred for the first time for assessment of PAD with a history of intermittent claudication and ankle brachial pressure of index of ≤0.9 were recruited. All subjects underwent a full echocardiogram, office blood pressure and 24 hour ambulatory blood pressure monitoring. Results: Out of 350 subjects screened, left ventricular mass measurements were available on 227 (65%). The prevalence of LVH indexed to body surface area was 50%. In a multiple regression model the factors independently related to LVH were age, sex and history of diabetes. There was no relation between presence of LVH and 24 hour blood pressure. Conclusion: LVH is prevalent in patients with PAD and is not associated with 24 hour blood pressure.

This thesis presents four studies investigating the phenomenon of post exercise hypotension in the human condition of pre (borderline)-hypertension. Study one investigated the effects of an acute bout of 30-minutes upright cycling on post exercise haemodynamics and compared the results to a non-exercise control condition. 9 pre-hypertensive males, mean arterial pressure (MAP) = 106 ± 5 mmHg (50 ± 10 yr), not on medication, were studied for 6 hours following 30-minutes of cycle exercise at 70% maximal oxygen consumption and following 30-minutes of seated rest. Results demonstrate that moderate intensity exercise exerts a modest fall (~6 mmHg) in arterial pressure with the hypotension sustained for 6-hours post exercise. The fall in arterial pressure equates to a significantly reduced after load when compared to both pre-exercise baseline and non-exercise control data taken at the same time of day. The arterial pressure responses transcended into a sustained reduction (20%) in systemic vascular resistance and reciprocal increase in vascular conductance for up to 2-hours post-exercise. Venous atrial natriuretic peptide (ANP) demonstrated an elevation (44%) following exercise and a significant decline (33%) in the post-exercise period mirroring the haemodynamic response. This research reveals that acute exercise is capable of sustained reductions in arterial pressure and vascular resistance beyond the usual labile fluctuations and that the octapeptide ANP may exert a modulatory influence over the post-exercise response. Increases in 02 tension beyond the physiological range induces complex effects on the circulatory system with a dominant vasoconstriction following hyperoxia. The purpose of study 2 was to assess the effects of hypoxic (16% 02) and hyperoxic (50% 62) exercise on subsequent haemodynamic control when compared with normoxia. 9 pre-hypertensive males, MAP = 106 ± 5 mmHg (50 ±10 yr), not on medication, performed 30-minutes of cycle exercise at 70% normoxic maximal oxygen consumption in hypoxia (16% O 2 ), hyperoxia (50% O 2) and normoxia(21% O2 ). Hyperoxic exercise blunted post-exercise haemodynamics by significantly attenuating the reductions (from normoxic baseline) in SVR (-45%, PO.05 vs. normoxic & hypoxic exercise immediately post-exercise) that persisted throughout 120-minutes recovery in normoxia (-35% vs. normoxic & hypoxic exercise, during recovery) and elicited a mildly hypertensive effect, with regards to MAP, whereas normoxic and hypoxic exercise elicited a hypotension compared to baseline (P < 0.05). Circulating ANP was decreased in the hyperoxic trial when compared with normoxic and hypoxic exercise [24.3 (13.4) v. 31.5 (16.3) and 29.6 (13.9) pg/ml, respectively; P < 0.05, pooled for state]. Changes in MAP were related to changes in ANP concentration only following hyperoxic exercise (r = 0.50, P < 0.01). These findings indicate that acute modest hyperoxia reflexively induces measurable physiological derangement partly explained by decreased circulating concentrations of ANP. Study three determined the role of free-radical mediated oxidative stress and redox regulation of circulating NO metabolism as a primary modulator of vascular tone following exercise in pre-hypertensive humans. Utilising the same cohort and exercise protocol as in study 1 venous blood was sampled from an antecubital vein. Plasma NO metabolites nitrate (NO" 3 ) and nitrite (NO"2 ) were determined fluorometrically, whilst S-Nitrosothiol (RSNO) concentrations were assayed by the Saville reaction Indirect markers of oxidative stress were determined spectrophotometrically detecting lipid hydroperoxides (LOOH). Exercise led to a delayed increase in LOOH by 60- minutes post-exercise (0.69 ± 0.13 v. 0.86 ± 0.18 umol/1, respectively, P < 0.05), that remained elevated until termination of the trial 6-hours post-exercise. NO'a significantly fell below baseline by 120-minutes post-exercise (10.8 ± 3.3 v. 1.1 ±1.1 u.mol/1, respectively, P < 0.05), remaining attenuated for the remainder of the study.NO'i and RSNO were unmodified in the post-exercise period. In parallel to this finding the data also indicates a significant blunting in the hyperaemic response [SVR decreased from a 31% reduction immediately (within 1-minute) post-exercise to -13 and 8% at 60- and 120-minutes post-exercise, respectively, P < 0.05] and reversal of the hypotension (P < 0.05) over the same time frame as the augmented lipid peroxidation and attenuated circulating NO~3. These results indicate that augmented oxidative stress exerts a deleterious effect on post-exercise haemodynamics and implicates a potential redox regulation pathway of NO as being a mechanism by which free radical-induced oxidative stress blunts the degree of PEH in the recovery period. The final study investigated the potential role of a redox-mediated regulation of circulating NO bioavailability as a modulator of the augmented vasoconstriction following hyperoxic exercise. The same cohort and exercise protocol were employed as in study 2 and venous blood was assayed for NO"3 , NO'a, RSNO, LOOK, & lipid /water-soluble antioxidant concentrations. Similar adverse haemodynamic effects were noted following hyperoxic exercise as reported previously in study 2. RSNO showed a significant increase following hypoxic exercise only (P < Q.Q5, state x time, interaction), whereas NO~3, NO~2 and LOOH failed to differ between conditions (P > 0.05, main effect for state [02] and state x time, interaction effects). Ascorbic acid was mobilised in response to hyperoxic exercise when compared to normoxia (P < 0.05, main effect for state [O2] and state x time, interaction effects) being significantly elevated by 120-minutes post-exercise in hyperoxia compared to normoxia and hypoxia [75.1 (31) v. 39.5 (18.3) v. 46.7 (14.2) |amol/l, respectively, P < 0.05]. This data demonstrates an effective endogenous antioxidant response and argues against a redox regulation pathway of NO metabolism as a primary mediator of blunted vasodilatation in this scenario. This elucidates a more complex regulation of arterial tone, resulting from a metabolic pathway independent of NO in older subjects with pre-hypertension. This work demonstrates that (1) aerobic exercise exerts a hypotensive effect in humans with pre-hypertension, (2) ANP plays a part in the vasodilatation following exercise, (3) Free-radical mediated oxidative stress & subsequent modulation of NO metabolism exerts a deleterious influence on post-exercise haemodynamics (4) Acute hyperoxic exercise induces a sustained vasoconstriction that is mediated via circulating ANP concentration but not by redox regulation of NO metabolism.

Childhood chronic kidney disease (CKD) is a devastating illness requiring life-long medical input, often progressing to end stage kidney disease (ESKD) requiring dialysis and renal transplantation. Despite an increasing number of children now surviving through childhood and early adulthood, heart disease remains one of the major causes of death in individuals with childhood-onset CKD as young adults and it is likely this relates to onset of pre-clinical cardiovascular disease developing during childhood. Arterial stiffening relates to the severity of CKD, being greatest in those with dialysis dependent CKD, and is thought to be driven, at least in part, by excess body weight, hypertension and metabolic changes associated with CKD but their contribution to arterial disease progression remains poorly understood. The relationship of blood pressure with arterial disease remains unclear in the paediatric literature. Previous studies performed in children pre-dialysis, those on dialysis and following kidney transplantation have measured pulse wave velocity (PWV) of the carotid-femoral pathway (i.e. mainly the aorta) and/or measures of carotid mechanics have been examined but these studies have been limited by lack of concurrent measures of carotid blood pressure (required to determine functional elasticity of the carotid artery). Furthermore, whilst the potential impact of age and blood pressure (BP) have been adjusted for, when comparing differences between children with and without CKD, this comparison has not been performed between age and blood pressure matched groups. The objectives of my thesis are to 1) to determine the use of an easy to perform, well tolerated technique to measure PWV in children. 2) to compare estimates of central aortic systolic pressure with that measured directly from catheter placed in the aortic root. 3) to determine typical estimates of systolic blood pressure amplification and 4) to determine the association of arterial function and structure with severity of childhood CKD and to examine the relation of these measures to blood pressure. 5) to design a controlled trial to evaluate effects of aggressive versus standard blood pressure control on cardiovascular target organ damage. My research findings report novel data relating to my project objectives. We compared two different techniques to measure PWV (volumetric and tonometric) and observed that the volumetric technique is easy to perform, well tolerated and reproducible when measurements are made by the same observer consecutively, but that the results are of the two techniques are not inter-changeable. My work for objective 2 and 3 measured central blood pressure at the aortic root at the time of arterial cannulation and confirmed that blood pressure measured in the arm differs from that close to the heart. We validated simple non-invasive methods to measure blood pressure in children and showed that peripheral systolic amplification is substantial, including those with and without hypertension and mild to advanced CKD, with a mean amplification of ~ 20 mmHg and thus may be relatively more important than in adults. In a cohort of children with and without CKD, we performed a comprehensive characterization of arterial biomechanics and observed that the changes in elastic properties of the carotid artery were related to increased blood pressure, and not to decreased glomerular filtration rate. Important limitations to this cross-sectional study include lack of knowledge of duration of both hypertension and CKD and lack of formal sample size calculation. Despite these limitations the results from my thesis suggest that blood pressure reduction may be an effective means to protect against arterial stiffening and needs to be evaluated using a controlled clinical trial. The design of such a trial is presented.

Increased arterial stiffness is a predictor of cardiovascular events and mortality across a diverse range of populations. Although gross-mechanical stiffness can be measured in vivo, in order to understand the pathological mechanisms it will be necessary to identify which local micro-structural remodelling events are the prime drivers of altered macro-mechanical function. However, characterisation of arterial structure by conventional histological approaches: i) commonly induces artefacts as a consequence of the sectioning process, ii) provides no insight into the three dimensional structure of the tissue and iii) is performed on unpressurised tissue. This project has set out to address these limitations by developing new micro computed x-ray tomography (micro-CT) methodologies which are capable of visualising the three dimensional structure of rat arteries. This new methodology was then been applied in combination with gross-and micro-mechanical testing and atomic force microscopy imaging to characterise the effects of both intra-luminal pressure and age on arterial structure and function. From these investigations it was clear that micro-CT could readily distinguish discrete tissue sub-structures in paraffin embedded tissues, including skin and arteries and that this imaging approach was compatible with complimentary histological and immunohistochemical analyses. Characterisation of the structure and mechanical function of carotid arteries in aged rats demonstrated localised stiffening in the adventitial layer and a change in the molecular structure of adventitial collagen. The effects of intra-luminal pressure on structure using micro-CT revealed changes in artery cross-sectional area, which suggest the artery wall may be compressible. Investigations into the effects of pressure on the molecular structure of adventitial collagen revealed an increase in periodicity at mean pressure. These findings together demonstrate that the adventitial layer has an important role in the development of arterial stiffness. Micro-CT can reveal novel information that improves our understating of artery structure and how artery structure changes during ageing.

The determination of required pressure level to provide an optimum treatment is an important task for vascular clinicians. This thesis is a first investigation including both venous and arterial femoral velocities and distal microcirculation of the forefoot to evaluate the effects of varying uniform external compression applied to the whole lower limb in humans. The ultrasound technique has been used to evaluate the maximal venous and arterial velocities in femoral common vessels. The microcirculation and the cutaneous oxygenation of the forefoot were recorded by laser Doppler fluxmetry and transcutaneous oxygen and carbon dioxide pressure measurements respectively. The findings of the present investigation support the concept that a uniform pressure applied to the full length of a healthy leg when the subject is in recumbent position should probably not exceed 10 mmHg, since significant impairment of both macro and microcirculation can be found. A database of information collected from twenty eight healthy subjects was established. Using this database and regression analysis, a new empirical model was produced which gave a hierarchical description of oxygen in terms of applied pressure and subject's characteristics. The developed model was expressed in terms of a cubic polynomial and was analysed in the content of catastrophy theory. This was appropriate to account for sudden changes in the data. Although the results obtained were based on this preliminary study, it appears that the predictive results are extremely encouraging and form a solid basis for future research. The observations of cubic forms in medical statistics as well as the inclusion of micro and macro in a single model are approaches that have been neglected in the past. A further area of apparent neglect appears to be in the careful selection of the sampling intervals to optimise information content of the database.

Cardiovascular disease varies by ethnicity in the UK. South Asians (SA) have higher coronary heart disease (CHD) and diabetes prevalence, while African-Caribbeans (AfC) have greater stroke, but intriguingly lower CHD rates despite higher blood pressures and diabetes risk than Europeans. Conventional risk factors do not fully explain such differences. This cross-sectional study tested the hypothesis that the hormones, vitamin D measured as 25(OH)D and aldosterone, would be independently associated with intermediate cardiovascular outcome markers in these ethnic groups. Community-dwelling men 40-80 years old (AfC: n=67, 55±10yr; SA: n=68, 55±10yr; European: n=63, 57±8yr) were sampled from Greater Manchester’s multi-ethnic population. The intermediate markers examined were aortic pulse wave velocity (aPWV), left ventricular (LV) mass and function, and carotid intima media thickness (CIMT), measured non-invasively by ultrasound, and hemodynamic profiling methods (the Arteriograph) in the total sample and by magnetic resonance imaging (MRI) in a subsample of 50. Adjusted for age, systolic blood pressure and diabetes, mean(SE) aPWV by the Arteriograph, was 0.5(0.2) m/s higher in SA than AfC and Europeans (p=0.01), which paralleled known cross-ethnic CHD risk differences in the UK. By MRI, aPWV along the descending aorta in SA was 0.7(0.3) and 0.8(0.3) m/s higher than that in AfC and Europeans, but aPWV along the aortic arch was not significantly different. Unlike aldosterone, 25(OH)D was independently and inversely correlated with aPWV (unstandardised B(SE)=-0.013[0.004] m/s, p<0.001), and partly explained the ethnic variation in aPWV. Similar inverse correlations were found between 25(OH)D and LV concentricity measured by echocardiography and MRI. Compared to Europeans, SA and AfC, had 21(3) and 14(3) nmol/L lower mean(SE) 25(OH)D, respectively (p<0.01). Mean(SE) of relative wall thickness, an index of LV concentricity by echocardiography, was 0.05(0.01) higher in SA and AfC than Europeans. Lower 25(OH)D levels were also associated with higher myocardial deformation rates measured by MRI myocardial tagging (n=50), supporting previous animal experimental evidence. A one standard deviation (SD) decrease in 25(OH)D was associated with a 0.38 SD increase in absolute systolic strain rate (p=0.003) and 0.22 SD rise in diastolic strain rate (p=0.04). Right and left CIMT showed different relations with 25(OH)D and aldosterone. Left-right CIMT differences varied by ethnicity and were related to SA ethnicity and aldosterone levels. Two related technical studies investigated the relatively new method of hemodynamic profiling, the Arteriograph, used here. The results suggested a standardisation method of aortic length estimation for purely central aPWV, which significantly improved aPWV agreement between the Arteriograph and MRI (reference method here), and was used for calibrating the Arteriograph aPWV in the above-mentioned results for the total sample. Future well-designed trials are necessary to investigate any cause-effect relationship between vitamin D deficiency and the unfavourable cardiovascular intermediate outcomes found here in a cross-sectional design and multi-ethnic background.

Uvod. Kardiovaskularne bolesti kao deo grupe hroničnih nezaraznih bolesti predstavljale su i predstavljaju vodeći uzrok obolevanja i umiranja u svetu. Brojni naučni dokazi potvrđuju da je arterijska hipertenzija glavni kardiovaskularni faktor rizika, a da postignute vrednosti krvnog pritiska niže od 140/90mmHg značajno smanjuju kardiovaskularni rizik, odnosno pojavu kardiovaskularnih događaja, prvenstveno infarkta miokarda i moždanog udara. Arterijska hipertenzija je najzastupljenije stanje koje se viđa u ustanovama primarne zdravstvene zaštite, a mere prevencije, rano dijagnostikovanje, lečenje i kontrola arterijske hipertenzije predstavljaju javno-zdravstveni izazov u svim zemljama sveta. Ciljevi. Ciljevi istraživanja su utvrđivanje prevalencije arterijske hipertenzije koja je pod kontrolom; utvrđivanje prevalencije i povezanosti metaboličkih faktora sa ishodom u kontroli krvnog pritiska; utvrđivanje prevalencije i povezanosti nezdravih stilova života sa ishodom u kontroli krvnog pritiska; utvrđivanje prediktora loše kontrole krvnog pritiska i izračunavanje 10-godišenjeg kardivaskularnog rizika. Metode. U studiju preseka (prevalencije) uključeno je 373 ispitanika oba pola starosti od 45 do 75 godina sa dijagnozom arterijske hipertenzije u kartonu koji su u periodu od oktobra 2015. godine do februara 2016. godine dolazili kod svog izabranog lekara. Prikupljanje podataka obavljeno je merenjem krvnog pritiska, antropometrijskim merenjima, biohemijskim analizama i anketiranjem popunjavanjem upitnika. Rezultati. Uzorak ispitanika je činilo 55% žena i 45% muškaraca prosečne starosti 59±6,3 godine. Utvrđena je niska učestalost arterijske hipertenzije pod kontrolom od 39,1%, a visoka učestalost metaboličkih faktora (44,5% predgojaznosti, 34% gojaznosti, 29% šećerne bolesti, 88,2% povišenih masnoća i 41,8% metaboličkog sindroma) kao i njihova povezanost sa ishodom u kontroli krvnog pritiska jer su ispitanici sa nekontrolisanim krvnim pritiskom najčešće imali dva faktora rizika (40,5%), dok su ispitanici sa kontrolisanim krvnim pritiskom najčešće imali jedan faktor rizika (45,9%). Utvrđeno je da su prosečne vrednosti sistolnog, dijastolnog pritiska i pulsa bile značajno (p<0,001) niže u grupi sa kontrolisanim pritiskom kao i da su ispitanici sa nekontrolisanim pritiskom imali značajno veći obim struka (p=0,006), metabolički sindrom (p<0,001) i značajno češće pili veći broj lekova (p<0,001). Utvrđena je visoka učestalost pušenja (26,3%) i visoka učestalost sedentarnog načina života (76,7%) kao i da znanja, stavovi i ponašanja ispitanika u vezi faktora rizika (pušenja, konzumiranja alkohola, fizičke neaktvnosti i prekomerne upotrebe soli) nisu na zadovoljavajućem nivou. Kao nezavisni prediktori arterijske hipertenzije koja nije pod kontrolom dobijeni su obim struka, telesna masa, indeks telesne mase, starost, vrednost pulsa, broj lekova koje ispitanici piju, pasivno pušenje, nesvesnost o postojanju arterijske hipertenzije, neznanje o štetnosti konzumiranja prekomerne količine alkohola, nepreležan infarkt miokarda i moždani udar. Izračunato je da je u visokom i veoma visokom riziku od neželjenih kardiovaskularnih događaja u desetogodišnjem periodu 2,7% ispitanika sa arterijskom hipertenzijom bez dijabetesa i 22,2% hipertenzivnih ispitanika sa dijabetesom. Zaključak. Potrebno je sprovođenje javno-zdravstveno vaspitnih i promotivnih aktivnosti u cilju povećanja znanja, promene stavova i ponašanja kod populacije sa arterijskom hipertenzijom usled loše kontrole krvnog pritiska i prisustva visoke učestalosti pridruženih faktora rizika koji utiču na njegovu kontrolu.
Introduction. Cardiovascular diseases, as part of a group of chronic noncommunicable diseases, have been and still are the leading cause of morbidity and mortality in the world. Numerous scientific proofs confirm that arterial hypertension is a major cardiovascular risk factor and that the achieved blood pressure values lower than 140/90mmHg significantly reduce cardio-vascular risk, or the appearance of cardio-vascular events, mainly myocardial infarction and stroke. Arterial hypertension is the most common condition that is seen in primary health care institutions and preventive measures, early diagnosis, treatment and control of arterial hypertension are a public health challenge in all countries of the world. Objectives. The objectives of the research were to determine the prevalence of arterial hypertension which is controlled; to determine the prevalence and correlation of the metabolic factors with the outcome in blood pressure control; to determine the prevalence and correlation of unhealthy lifestyles with the outcome in blood pressure control; to determine the predictors of poor blood pressure control and calculate a 10-year cardiovascular risk. Methods. The cross-sectional study (of prevalence) included 373 respondents of both sexes aged 45 to 75 years diagnosed with arterial hypertension who in the period from October 2015 to February 2016 visited their chosen doctor. Data collection was performed by measuring blood pressure, anthropometric measurements, biochemical analyses and surveying by filling out a questionnaire. Results. The sample consisted of 55% women and 45% men, of mean age of 59±6.3 years. The results showed low incidence of arterial hypertension under control of 39.1%, and high incidence of metabolic factors (44.5% of overweight, 34% of obesity, 29% of diabetes mellitus, 88.2% of elevated fat and 41.8% of the metabolic syndrome) as well as their association with the outcome in blood pressure control as the respondents with uncontrolled blood pressure usually had two risk factors (40.5%), while the group with controlled blood pressure usually had one risk factor (45.9%). It was found that the average values of systolic, diastolic blood pressure and heart rate were significantly (p<0.001) lower in the group with controlled blood pressure, as well as that the respondents with uncontrolled pressure had a significantly greater waist circumference (p=0.006), the metabolic syndrome (p<0.001) and more often drunk greater number of medicines (p<0.001). There was a high prevalence of smoking (26.3%) and a high incidence of sedentary lifestyle (76.7%) and it was found that knowledge, attitudes, and behaviors of the respondents related to risk factors (smoking, alcohol consumption, physical inactivity and excessive use of salt) were not satisfactory. As independent predictors of arterial hypertension which was not under the control, the study obtained waist circumference, body weight, body mass index, age, heart rate value, the number of medicines that the respondents drunk, second-hand smoking, unawareness of the existence of arterial hypertension, inexperience on the harmful effects of excessive amounts of alcohol, not overcome myocardial infarction and stroke. It was calculated that 22.2% of hypertensive respondents with diabetes and 2.7% of respondents with arterial hypertension without diabetes were in the high and very high risk of adverse  Conclusion. It is necessary to implement public-health educational and promotional activities in order to increase the knowledge, changes in the attitudes and behavior of the population with arterial hypertension due to the poor control of blood pressure and the presence of the high incidence of associated risk factors affecting its control.

Cilj: Cilj ovog istraživanja bio je da se utvrde promene koje arterijska hipertenzija dvojakim mehanizmima (dnevno-noćnim ritmom i svojim trajanjem) ostavlja na funkciju i geometriju leve pretkomore i komore srca. Ispitanici i metode: u ovo istraživanje bilo je uključeno 180 ispitanika koji su bili podeljeni u ispitivane grupe u odnosu na dnevno-noćni ritam arterijskog krvnog pritiska tokom 24-časovnog monitoringa arterijskog krvnog pritiska i to na sledeći način: grupa ispitanika sa očuvanim dnevno-noćnim ritmom arterijskog krvnog pritiska sastojala se od ukupno 90 ispitanika, a grupu onih sa narušenim dnevno-noćnim ritmom arterijskog krvnog pritiska takođe je činilo 90 ispitanika. U svakoj od ovih grupa izvršena je dodatna podela ispitanika prema dužini trajanja arterijske hipertenzije na one kod kojih je arterijska hipertenzija trajala do 5 godina, one kod kojih je trajala od 5 do 10 godina i na one sa trajanjem arterijske hipertenzije više od 10 godina. Svim ispitanicima rađen je incijalno 24-časovni ambulantni monitoring arterijskog krvnog pritiska, a nakon toga i ehokardiografski pregled radi određivanja parametara morfologije leve pretkomore i komore, kao i dijastolne funkcije leve komore. Rezultati i diskusija: nakon statističke obrade podataka dobijeni su rezultati koji ukazuju da se dijastolna disfunkcija stepena većeg od I statistički značajno češće (p=0,011) uočava kod onih ispitanika koji nemaju očuvan dnevno-noćni ritam arterijskog krvnog pritiska. Narušen dnevno-noćni ritam arterijskog krvnog pritiska takođe dovodi do povećanja indeksirane mase miokarda leve komore prema površini tela ispitanika (LVM/BSA) – p=0,001; do zadebljanja zidova leve komore (IVS/PLW) – p=0,025, kao i do smanjenja sistolne brzine miokarda na nivou septalnog dela mitralnog anulusa (s’) - p<0,0005. Pored ovoga, u grupi onih sa narušenim dnevno-noćnim ritmom arterijskog krvnog pritiska primećeno je češće prisustvo ekscentrične hipertrofije miokarda leve komore (p=0,027). U odnosu na geometriju i funkciju leve pretkomore, narušen dnevno-noćni ritam arterijskog krvnog pritiska dovodi do promena u smislu povećanja antero-posteriornog dijametra leve pretkomore (LA)-p=0,003; maksimalnog volumena leve pretkomore u komorskoj sistoli (LAVs) –p=0,007; indeksiranog LAVs prema površini tela ispitanika (LAVs/BSA)-p<,0005; E/e’ odnosa –p=0,040; rezervoarnog strain-a leve pretkomore (PLAS)- p=0,004; krutosti leve pretkomore (stiffness)-p=0,047, kao i brzine propagacije talasa kroz mitralni otvor (Vp)-p=0,029. Sa povećanjem dužine trajanja arterijske hipertenzije takođe su pokazane promene u morfologiji i funkciji leve pretkomore i leve komore srca. Dijastolna disfunkcija stepena većeg od I retko je bila uočena u grupi onih koji su arterijsku hipertenziju lečili kraće od 5 godina, a njeno prisustvo u ispitivanim grupama trajanja od 5 do 10 godina i duže od 10 godina bilo je statistički značajno češće (p<0,0005). Takođe, sa trajanjem arterijske hipertenzije statistički značajno se menjaju i parametri leve komore za koje smo pokazali da su pogoršani kada dnevno-noćni ritam arterijskog krvnog pritiska nije očuvan, s tim što smo ovde uočili i značajne promene u smislu postojanja lošijih vrednosti strain-a leve komore (LVGS)-p<0,0005. Na sličan način kao i u odnosu na dnevno-noćni ritam arterijskog krvnog pritiska, menjao se predominantni oblik hipertrofije miokarda leve komore, te je uočeno značajno češće (p=0,017) prisustvo ekscentrične hipertrofije kod ispitanika koji su duže lečili arterijsku hipertenziju. Uz ove promene, sa trajanjem arterijske hipertenzije, uočene su i promene sledećih ehokardiografskih parametara leve pretkomore (p<0,0005): LA, LAVs, LAVs/BSA, E/e’, PLAS, stiffness, Vp. Na kraju, formiran je i model za dijagnostiku dijastolne disfunkcije stepena većeg od I koji je testiran na 30 novih ispitanika i koji se pokazao kao kvalitetan uz visoku senzitivnost i specifičnost. Zaključak: arterijska hipertenzija dnevno-noćnim oscilacijama (ritmom), ali i svojim trajanjem dovodi do promena u funkciji i geometriji leve pretkomore i komore srca. Noviji ehokardiografski parametri (PLAS, LVGS, stiffness) su dobri pokazatelji ranih promena na nivou leve pretkomore i komore srca kod pacijenata sa arterijskom hipertenzijom.
Objective: The aim of this study was to determine the changes that arterial hypertension by its dual mechanisms (circadian rhythm and its duration) leaves on the function and geometry of left atrium and left ventricle of the heart. Respondents and Methods: This study involved 180 subjects who were divided into examined groups in relation to the circadian arterial blood pressure rhythm during 24-hour monitoring of arterial blood pressure, as follows: group of subjects with preserved circadian rhythm of arterial blood pressure consisted of a total of 90 subjects, and a group of those with impaired circadian rhythm of arterial blood pressure also comprised 90 subjects. In each of these groups an additional division of subjects was performed according to the duration of arterial hypertension to those whose arterial hypertension lasted up to 5 years, those in whom it lasted 5-10 years and those with duration of arterial hypertension for more than 10 years. All participants received an incisional 24-hour ambulatory monitoring of arterial blood pressure, followed by an echocardiographic examination to determine the morphology parameters of the left atrium and ventricle, as well as the diastolic functions of the left ventricle. Results and discussion: after statistical data processing, results have been obtained indicating that diastolic dysfunction of a level greater than I statistically significantly more frequently (p = 0.011) was observed in those subjects who didn’t have preserved circardian rhythm of arterial blood pressure. A non-dipper circadian arterial blood pressure rhythm also led to an increase in the indexed left ventricular myocardial mass according to the body surface of the respondent (LVM / BSA) - p = 0.001; to the increase in the wall thickness of the left ventricle (IVS / PLW) - p = 0.025, as well as to the decrease in systolic myocardial velocity at the level of the septal portion of the mitral anulus (s') - p <0.0005. In addition, in the group of those with impaired circadian rhythm of arterial blood pressure, a more frequent presence of eccentric hypertrophy of the left ventricular myocardium (p = 0.027) was observed. In relation to the geometry and left atrial function, the circadian rhythm of arterial blood pressure led to a change in terms of an increase in the antro-posterior diameter of the left atrium (LA) -p = 0.003; maximum left ventricular volume in ventricular systole (LAVs) -p = 0.007; indexed LAVs according to the surface of the respondent’s body (LAVs / BSA) -p <, 0005; E / e 'ratio-p = 0.040; reservoar strain (PLAS) - p = 0.004; stiffness -p = 0.047, as well as the velocity propagation across the mitral opening (Vp) -p = 0.029. With increasing duration of arterial hypertension, changes in morphology and left atrial and left ventricular functions were also demonstrated. Diastolic dysfunction of a grade greater than I was rarely observed in the group of those who had been treating arterial hypertension for up to 5 years, and its presence in the investigated groups with duration of 5 to 10 years and for more than 10 years was statistically significantly more common (p <0.0005). Also, with the duration of arterial hypertension, the parameters of the left ventricle were also significantly changed-the same for which we showed that they were worsened when the circadian rhythm of arterial blood pressure was not preserved, but beside that we noticed significant changes in the sense of the existence of less negative values of strain- the left ventricle global strain (LVGS) -p <0.0005. In a similar way to the circadial rhythm of arterial blood pressure, the prevalent form of myocardial left ventricular hypertrophy changed, and the presence of eccentric hypertrophy in patients with longer arterial hypertension duration was significantly more frequent (p = 0.017). In addition to these changes, with duration of arterial hypertension, changes in the following echocardiographic parameters of the left atrium (p <0.0005) were observed: LA, LAVs, LAVs / BSA, E / e ', PLAS, stiffness, Vp. Finally, a model for the diagnosis of diastolic dysfunction of a degree greater than I was formed and afterwards tested on 30 new subjects and it proved to be of good quality with high sensitivity and specificity. Conclusion: arterial hypertension by its duration and day-night oscillations (rhythm) leads to changes in the function and geometry of the left atrium and left ventricle of the heart. The latest echocardiographic parameters (PLAS, LVGS, stiffness) are good indicators of early changes of left atrium and left heart ventricle in patients with arterial hypertension.

Uvod: Traumatsko moždano oštećenje (TMO) predstavlja globalni zdravstveni problem koji pogađa oko 10 miliona ljudi godišnje širom sveta. Teška traumatska moždana oštećenja (TTMO) čine 10% svih TMO i imaju visoku stopu mortaliteta i neizvestan oporavak. Ranije prepoznavanje sistemskih faktora koji utiču na ishod lečenja može da ima značajan uticaj na pravovremeno započinjanje terapijskih mera i smanjivanje morbiditeta i mortaliteta. Cilj istraživanja: Identifikovati sistemske faktore koji imaju značajan uticaj na ishod lečenja povređenih sa TTMO u Jedinici intenzivnog lečenja (JIL) tokom prvog dana hospitalizacije. Metodologija: Ispitivanje je sprovedeno kao retrospektivno-prospektivna studija koja je obuhvatila 115 povređenih ispitanika sa TTMO koji su hospitalizovani u JIL Urgentnog centra Kliničkog centra Vojvodine (UC KCV) u periodu od 1.01.2014.-1.10.2017. Iz medicinske dokumentacije, za svakog ispitanika uključenog u istraživanje su uzeti u razmatranje i analizu sledeći parametri u toku prvih 24 časa od momenta prijema u JIL: demografske i opšte karakteristike ispitanika od značaja za istraživanje i sistemski prediktivni faktori (sistolni i srednji arterijski pritisak- SAP/MAP, glikemija-ŠUK, telesna temperatura-TT, pH, parcijalni pritisak kiseonika-PaO2 i parcijalni pritisak ugljem dioksida- PaCO2) registrovani u pet vremenskih tačaka (0h, 6h, 12h,18h, 24h). Svi gore navedeni podaci su posmatrani i analizirani kao prediktorski faktori tj. nezavisne varijable u odnosu na zavisnu varijablu „ishod lečenja“ definisanu kao Glazgovska skala ishoda (Glasgow outcome scale-GOS) nakon otpusta povređenih iz JIL na Kliniku za neurohirurgiju KCV i GOS nakon otpusta iz Klinike za neurohirurgiju KCV i „tok lečenja“ definisan kroz dužinu boravka povređenih u JIL UC KCV, dužinu boravka na Klinici za neurohirurgiju KCV, odnosno ukupno trajanje hospitalizacije u KCV, kao i otpust kući ili u odgovarajući rehabilitacioni centar. Statistička analiza je izvršena pomoću statističkog paketa IBM SPSS 23. Podaci su predstavljeni tabelarno i grafički, a statistička značajnost određivana je na nivou p < 0,05. Prikupljeni podaci su obrađeni adekvatnim statističkim metodima. Rezultati: Sistemski faktori koji su se izdvojili kao prediktori smrtnog ishoda (GOS 1) kod povređenih sa TTMO tokom prvog dana boravka u JIL su upotreba vazoaktivne potpore i glikemija. Upotreba vazoaktivne potpore povećava verovatnoću za smrtni ishod 4,7 puta (OR=0,214; 95%CI: 0,096-0,479; p<0,05). i vrednosti glikemije > 10 mmol/l povećavaju verovatnoću za smrtni ishod u nultom satu (OR= 0,240, 95%CI: 0,087-0,662; p=0,05) i u 24 satu (OR=0,206, 95%CI: 0,037 – 0,929; p=0,05). Sa svakim porastom telesne temperature za jednu jedinicu u posmatranom intervalu raste verovatnoća za pozitivan ishod (OR =2,118 , 95%CI: 1,097 – 4,091; p<0,05) i vrednosti glikemije u intervalu od 4-8 mmol/l povećavaju verovatnoću za pozitivan ishod 2,5 puta. Sistemski faktori koji su se izdvojili u smislu predikcije ishoda lečenja ispitanika nakon otpusta iz JIL su vrednosti glikemije i telesna temperatura. Vrednost glikemije na prijemu u intervalu od 6,9 do 7,4 mmol/l povećavaju verovatnoću boljeg oporavka (GOS 4-5 vs. GOS 2-3). Niže vrednosti glikemiije u narednim vremenskim tačkama (6h, 12h, 18h) takođe povećavaju verovatnoću za bolji oporavak. Ukoliko je telesna temperatura u 6-om i 12-om satu, viša od 36,5 °C veća je verovatnoća za bolji neurološki oporavak, prilikom otpusta iz JIL, odnosno Klinike za neurohirurgiju KCV. Ispitanici koji su imali više vrednosti telesne temperature su imali duže trajanje hospitalizacije (OR=4,096; 95%CI; 0,709-7,483;p<0,05). Na dužinu boravka u JIL, kao i na otpust kući ili odgovarajući rehabilitacioni centar nije imao uticaj nijedan posmatrani sistemski faktor. Zaključak: Sistemski prediktivni faktori toka i ishoda lečenja povređenih sa TTMO su upotreba vazoaktivne potpore, glikemija i telesna temperatura.
Introduction: Traumatic brain injury (TBI) is a global health problem that affects about 10 million people worldwide annually. Severe traumatic brain injury (STBI) account for 10% of all TBI and has high morbidity and unreliable recovery. Early recognition of systemic factors that affect the treatment outcome can have a significant impact on the timely initiation of therapeutic measures and the reduction of morbidity and mortality. The objective of the research: to identify systemic factors that have a significant impact on the treatment outcome of the STBI patients in the Intensive Care Unit (ICU) during the first day of hospitalization. Methodology: The study was conducted as a retrospective-prospective study that included 115 injured patients with STBI who were hospitalized in the ICU, Emergency Center (EC) of the Clinical Center of Vojvodina (CCV) in the period from 01.01.2014 to 1.10.2017. From the medical documentation, for each participant involved in the research, the following parameters within the first 24 hours after the admission were considered and analyzed: demographic and general characteristics of the participants of importance for research and systemic predictive factors (systolic and mean arterial pressure-SAP / MAP, glycemia, body temperature -TT, pH, partial pressure of oxygen-PaO2 and partial pressure of carbon dioxide-PaCO2) registered at five time points (0h, 6h, 12h,18h, 24h). All of the above data were observed and analyzed as predictors, ie, independent variables in relation to the dependent variable "treatment outcome" defined as the Glasgow Outcome Scale (GOS) after the transfer from the ICU to the Clinic of neurosurgery of the CCV and GOS after discharge from a Clinic of neurosurgery and "treatment course" defined by length of stay in ICU, or the total duration of hospitalization in CCV, as well as the release to the home or the appropriate rehabilitation center. Statistical analysis was performed using the IBM SPSS 23 statistical package. The data are presented in tables and graphs, and the statistical significance was determined at p <0.05. The collected data were processed with adequate statistical methods. Results: Systemic factors that had predictive value for the lethal outcome (GOS 1) in STBI during the first day of ICU stay were the use of vasopressors and glycemia. The use of vasopressors increases the likelihood of fatal outcome 4.7 times (OR= 0,214; 95%CI: 0,096-0,479; p<0,05) and glycemic values > 10 mmol/l increase the likelihood of fatal outcome on admission (OR=0,240, 95%CI: 0,087-0,662; p=0,05) and after 24 hours (OR=0,206, 95%CI: 0,037 – 0,929; p=0,05). With each increase in body temperature for one unit in the observed interval, the probability of a positive outcome increases (OR=2,118, 95%CI: 1,097 – 4,091;p<0,05) and glycemic values in the range 4-8 mmol/l increase the probability of a positive outcome 2.5 times. Systemic factors that predict the treatment outcome of the patients after their discharge from ICU are glycemia and body temperature. The blood sugar on admission in the ICU in the range from 6.9 to 7.4 mmol/l increases the opportunity of a better recovery (GOS 4-5 vs. GOS 2-3). Lower glycemic values at the next time points (6h, 12h, 18h) also increase the opportunity of a better recovery. If the body temperature in the 6th and 12th-hour postadmission is higher than 36.5° C, the greater opportunity for better neurological improvement when the patient is discharged from ICU, or from the Clinic of neurosurgery. Participants who had higher values of body temperature had a longer duration of hospitalization (OR 4.096; 95% CI; 0.709-7.483;p<0,05). The length of the stay in ICU, as well as the release to the home or the appropriate rehabilitation center, was not affected by any observed systemic factor. Conclusion: Systemic predictive flow factors and outcome of treatment factors with STBI use of vasopressors, glycemia and body temperature.

La maladie rénale chronique (MRC) affecte environ 10% de la population adulte et est associée à un risque élevé de progression vers l’insuffisance rénale terminale (IRT), d’événements cardiovasculaires et de décès précoce. Des mesures sont recommandées pour prévenir la progression et les complications de la MRC, mais elles sont souvent basées sur un niveau de preuve faible ou sur la seule opinion d’experts. Dans cette thèse, nous avons utilisé des données observationnelles pour évaluer les pratiques cliniques dans deux domaines clés de la MRC : les abords artérioveineux (AV) en hémodialyse et le contrôle de l’hypertension artérielle (HTA) dans la MRC non terminale. Avec le registre national REIN des traitements de suppléance de l'IRT, nous avons montré que seuls 56% des 53 092 patients adultes incidents en hémodialyse de 2005 à 2013 avaient une voie d’abord AV (fistule ou pontage) créée, telle que recommandée, avant le démarrage de la dialyse, dont 16% étaient non fonctionnelles, nécessitant l'utilisation d'un cathéter associé à une sur-mortalité. La conversion en abord AV fonctionnel était associée à un meilleur pronostic, mais concernait dans les trois premières années de dialyse moins de deux patients sur trois ayant démarré sur cathéter. Dans l’étude de cohorte CKD-REIN, chez 1658 patients avec une MRC modérée à sévère, nous avons mis en évidence un moins bon contrôle de l'HTA et des niveaux de pression artérielle systolique plus élevés en lien avec des apports élevés en sodium, mais pas avec des apports faibles en potassium, évalués sur échantillon urinaire ponctuel. Le ratio sodium/potassium urinaire n'était pas plus discriminant que le sodium seul. Enfin, grâce au réseau International Network of Chronic Kidney Disease cohorts (iNET-CKD), qui inclut 17 cohortes sur 4 continents (N=34 602 patients avec un débit de filtration glomérulaire estimé < 60 mL/min/1,73 m2) nous avons mis en lumière le contrôle médiocre de l’HTA en général dans la MRC au regard des recommandations, avec d'importantes variations entre pays (27 à 61% de pression artérielle ≥140/90 mm Hg) expliquées en partie par les caractéristiques des patients et associées à des profils de traitements antihypertenseurs très différents. En conclusion, cette thèse pointe des écarts importants aux recommandations dans la prise en charge de la MRC en vie réelle et des pistes de prévention des complications liées aux abords AV et un meilleur contrôle de l'HTA
Chronic kidney disease (CKD) affects about 10% of the adult population and is associated with high risk of end-stage kidney disease (ESKD), cardiovascular complications, and premature death. Guidelines recommend a number of measures for the prevention of CKD progression and complications, but these recommendations are often based on low evidence or expert opinion. In this thesis, we used observational data to assess clinical practices in two key areas of CKD: arteriovenous (AV) access for hemodialysis, and hypertension control in moderate to severe CKD. Using data from the French REIN registry of renal replacement therapy for ESKD, we showed that only 56% of the 53,092 adult incident patients on hemodialysis from 2005 through 2013 had an AV access (either fistulae or grafts) created at hemodialysis initiation as recommended, of which 16% were nonfunctional, requiring catheter use associated with high mortality risk. Conversion into functional AV access was associated with better outcome, but less than two out of three patients starting hemodialysis with a catheter experienced this conversion within 3 years after dialysis start. In the CKD-REIN cohort study, among 1658 patients with moderate to severe CKD, we found less hypertension control and higher systolic blood pressure to be associated with higher sodium intake assessed from spot urine, but not with lower potassium intake. Spot urinary sodium/potassium ratio did not appear to add value than sodium alone for patient monitoring. Finally, using data from the International Network of Chronic Kidney Disease cohorts (iNET-CKD), including 17 cohort studies over 4 continents (N=34,602 patients with an estimated glomerular filtration rate < 60 mL/min/1.73 m2), we highlighted a global poor hypertension control in CKD with regards to recommendations, with large variations across countries (from 27 to 61% blood pressure ≥140/90 mm Hg). These variations are partly explained by patients’ characteristics, and associated with very different antihypertensive treatment profiles. In conclusion, this thesis points out major gaps between guideline recommendations and CKD management in real life, and provide clues for the prevention of AV access-related complications and better hypertension control

Peripheral vascular grafts are used for the treatment of peripheral arterial disease and arteriovenous grafts for vascular access in end stage renal disease. The development of neo-intimal hyperplasia and thrombosis in the distal anastomosis remains the main reason for occlusion in that region. The local haemodynamics produced by a graft in the host vessel is believed to significantly affect endothelial function. Single spiral flow is a normal feature in medium and large sized vessels and it is induced by the anatomical structure and physiological function of the cardiovascular system. Grafts designed to generate a single spiral flow in the distal anastomosis have been introduced in clinical practice and are known as spiral grafts. In this work, spiral peripheral vascular and arteriovenous grafts were compared with conventional grafts using ultrasound and computational methods to identify their haemodynamic differences. Vascular-graft flow phantoms were developed to house the grafts in different surgical configurations. Mimicking components, with appropriate acoustic properties, were chosen to minimise ultrasound beam refraction and distortion. A dual-beam two-dimensional vector Doppler technique was developed to visualise and quantify vortical structures downstream of each graft outflow in the cross-flow direction. Vorticity mapping and measurements of circulation were acquired based on the vector Doppler data. The flow within the vascular-graft models was simulated with computed tomography based image-guided modelling for further understanding of secondary flow motions and comparison with the experimental results. The computational assessments provided a three-dimensional velocity field in the lumen of the models allowing a range of fluid dynamic parameters to be predicted. Single- or double-spiral flow patterns consisting of a dominant and a smaller vortex were detected in the outflow of the spiral grafts. A double- triple- or tetra-spiral flow pattern was found in the outflow of the conventional graft, depending on model configuration and Reynolds number. These multiple-spiral patterns were associated with increased flow stagnation, separation and instability, which are known to be detrimental for endothelial behaviour. Increased in-plane mixing and wall shear stress, which are considered atheroprotective in normal vessels, were found in the outflow of the spiral devices. The results from the experimental approach were in agreement with those from the computational approach. This study applied ultrasound and computational methods to vascular-graft phantoms in order to characterise the flow field induced by spiral and conventional peripheral vascular and arteriovenous grafts. The results suggest that spiral grafts are associated with advanced local haemodynamics that may protect endothelial function and thereby may prevent their outflow anastomosis from neo-intimal hyperplasia and thrombosis. Consequently this work supports the hypothesis that spiral grafts may decrease outflow stenosis and hence improve patency rates in patients.

As avultadas taxas de mortalidade e morbilidade cardiovascular que assolam o mundo ocidental têm vindo a despertar vasto interesse, tanto de ordem social como clínica e económica, em desenvolver soluções que actuem ao nível da vigilância do paciente e da prevenção. A potencial utilidade de uma avaliação exacta, contínua, não-invasiva e de longo-termo do estado de saúde cardiovascular é largamente acreditada; neste contexto, a pressão arterial sanguínea, na qualidade de um dos parâmetros cardiovasculares mais informativos e dinâmicos, assume um papel de suma importância. Contudo, ainda não existe nenhum método não-invasivo clinicamente validado para determinar a pressão arterial de forma contínua. Posto isto, no presente estudo explorou-se, do modo mais próximo possível ao nível do batimento cardíaco, a dependência da pressão arterial com intervalos de tempo de natureza vascular e sistólica tais como o PTT, o PAT e o PEP, de acordo com os pressupostos teóricos estabelecidos por Möens-Korteweg e Hughes. Adicionalmente, com o intuito de obter esclarecimentos acerca das (não consensuais) fronteiras experimentais do PTT capazes de lhe proporcionar maiores níveis de exactidão, determinou-se este intervalo por intermédio de sete abordagens distintas, uma das quais de natureza inédita, inclusive. Foram adquiridos dados de ECG, PPG e HS para sete indivíduos e determinados os intervalos de tempo pretendidos. Também se teve acesso a uma base de dados de constituição semelhante, cedida pela Philips Research Europe. Subsequentemente, realizou-se uma avaliação estatística baseada em três ferramentas (informação mútua, coeficiente de correlação e erro de predição) estabelecida entre as pressões arteriais estimada e experimentalmente aferida, esta última com recurso a um aparelho oscilométrico (regime meramente discreto). Contudo, devido às limitações experimentas, aliadas à escassez dos dados disponíveis e a eventuais desajustes algorítmicos, não foi possível discernir nenhuma tendência ou tirar conclusões sólidas com base na avaliação estatística efectuada. Os estudos relatados apresentam, portanto, uma natureza prototípica, sem no entanto se desvalorizar o seu conceito, métodos e estratégias – que justificam, sem dúvida, futuros desenvolvimentos