High blood pressure, also called hypertension is one of the most common worldwide diseases afflicting humans and is a major risk factor for stroke, myocardial infarction, vascular disease, and chronic kidney disease. If blood pressure is controlled and oscillations in the hemodynamic variables are reduced, patients experience fewer complications after surgery. In clinical practice, this is usually achieved using manual drug delivery. Given that different patients have different sensitivity and reaction time to drugs, determining manually the right drug infusion rates may be difficult. This is a problem where automatic drug delivery can provide a solution, especially if it is designed to adapt to variations in the patient’s conditions. This research work presents an investigation into the development of abnormal blood pressure (hypertension) controllers for postoperative patients. Control of the drugs infusion rates is used to simultaneously regulate the hemodynamic variables such as the Mean Arterial Pressure (MAP) and the Cardiac Output (CO) at the desired level. The implementation of optimal control system is very essential to improve the quality of patient care and also to reduce the workload of healthcare staff and costs. Many researchers have conducted studies earlier on modelling and/or control of abnormal blood pressure for postoperative patients. However, there are still many concerns about smooth transition of blood pressure without any side effect. The blood pressure is classified in two categories: high blood pressure (Hypertension) and low blood pressure (Hypotension). The hypertension often occurred after cardiac surgery, and the hypotension occurred during cardiac surgery. To achieve the optimal control solution for these abnormal blood pressures, many methods are proposed, one of the common methods is infusing the drug related to blood pressure to maintain it at the desired level. There are several kinds of vasodilating drugs such as Sodium Nitroprusside (SNP), Dopamine (DPM), Nitro-glycerine (NTG), and so on, which can be used to treat postoperative patients, also used for hypertensive emergencies to keep the blood pressure at safety level. A comparative performance of two types of algorithms has been presented in chapter four. These include the Internal Model Control (IMC), and Proportional-Integral-Derivative (PID) controller. The resulting controllers are implemented, tested and verified for three sensitivity patient response. SNP is used for all three patients’ situation in order to reduce the pressure smoothly and maintain it at the desire level. A Genetic Algorithms (GAs) optimization technique has been implemented to optimise the controllers’ parameters. A set of experiments are presented to demonstrate the merits and capabilities of the control algorithms. The simulation results in chapter four have demonstrated that the performance criteria are satisfied with the IMC, and PID controllers. On the other hand, the settling time for the PID control of all three patients’ response is shorter than the settling time with IMC controller. Using multiple interacting drugs to control both the MAP and CO of patients with different sensitivity to drugs is a challenging task. A Multivariable Model Reference Adaptive Control (MMRAC) algorithm is developed using a two-input, two-output patient model. Because of the difference in patient’s sensitivity to the drug, and in order to cover the wide ranges of patients, Model Reference Adaptive Control (MRAC) has been implemented to obtain the optimal infusion rates of DPM and SNP. This is developed in chapters five and six. Computer simulations were carried out to investigate the performance of this controller. The results show that the proposed adaptive scheme is robust with respect to disturbances and variations in model parameters, the simulation results have demonstrated that this algorithm cannot cover the wide range of patient’s sensitivity to drugs, due to that shortcoming, a PID controller using a Neural Network that tunes the controller parameters was designed and implemented. The parameters of the PID controller were optimised offline using Matlab genetic algorithm. The proposed Neuro-PID controller has been tested and validated to demonstrate its merits and capabilities compared to the existing approaches to cover wide range of patients. / Libyan Ministry of Higher Education scholarship

Dans le but de vérifier l’impact d’un changement soudain dans l’agrégation érythrocytaire sur certains paramètres cardiovasculaires, une transfusion par échange sanguin du tiers du volume a été effectuée avec du sang hyperagrégeant chez le rat de souche Brown Norway. La pression caudale, le volume cardiaque systolique, la fraction d’éjection, le débit cardiaque, le rythme cardiaque et la résistance périphérique à l’écoulement sanguin ont été observés non-intrusivement sur 19 jours suite à la transfusion. Les rats ont été sacrifiés plus d’un mois suivant la transfusion et une étude ex vivo de la réponse à deux agents dilatateurs (l’acétylcholine et le nitroprussiate de sodium) a été menée sur les artérioles mésentériques. Des variations des paramètres cardiovasculaires, soit le débit, le volume systolique et la résistance périphérique, ont été remarquées dans les trois premiers jours posttransfusion. Une résistance du muscle vasculaire lisse au monoxyde d’azote a été notée chez les rats transfusés au sang hyperagrégeant alors qu’aucune dysfonction endothéliale n’était apparente en réponse à l’acétylcholine. / The aim of this study was to evaluate the effects of an acute change in erythrocyte aggregation on cardiovascular parameters by exchanging one third of the blood volume with hyperaggregating blood in the Brown Norway rat model. Values of caudal pressure, systolic cardiac volume, ejection fraction, cardiac output, heart rate and peripheral resistance to blood flow were observed non-invasively over 19 days after transfusion. The rats were sacrificed after more than a month following the procedure and an ex vivo study in response to pharmacological agents (acetylcholine and sodium nitroprussiate) was performed on mesenteric arterioles. Variations in cardiac output, systolic volume and peripheral resistance were noted for the first three days post-transfusion. The vascular smooth muscles of rats transfused with the hyperaggregating erythrocytes seemed to have developed a resistance to nitric oxide but no endothelial dysfunction was observed in response to acetylcholine.

Estudos demonstram que o treinamento aeróbio é capaz de reduzir a razão parede/luz (RP/L) de arteríolas musculares esqueléticas e reduzir a pressão arterial média, PAM (em hipertensos), além de causar bradicardia de repouso e aumentar a densidade de capilares e vênulas (em hipertensos e normotensos) após 13 semanas de treinamento. Investigamos em ratos normotensos (WKY, Wistar Kyoto) e hipertensos espontâneos (SHR) as alterações estruturais da microcirculação muscular esquelética, cardíaca e renal, relacionando-as aos valores de PAM e frequência cardíaca (FC) em diferentes fases de um protocolo de treinamento. Para tal, WKY e SHR (2 meses de idade) foram submetidos ao protocolo de treinamento físico de baixa intensidade por tempos crescentes (semanas 0, 1, 2, 4, 8 e 12) ou mantiveram-se sedentários (semanas 0 e 12). Ao final de cada tempo de estudo foram mensurados de modo direto a PAM e a FC e coletados coração, rim e músculos temporal, sóleo e gastrocnêmio. Realizou-se análise da RP/L e quantificação de capilares e vênulas (através do ácido periódico de Schiff). O treinamento aeróbio aumentou a densidade capilar e venular de WKY e SHR (apenas em territórios exercitados e com maior magnitude nos hipertensos), em seguida causou redução da razão parede/luz das arteríolas musculares esqueléticas (apenas em SHR, precocemente e em maior magnitude em territórios exercitados) e só então reduziu a PAM de SHR e a FC de WKY e SHR. A partir dos resultados obtidos, podemos dizer que alterações estruturais da microcirculação antecedem a melhora dos níveis pressóricos de hipertensos e ainda, são capazes de proporcionar melhoras vasculares aos normotensos / Previous observations have shown that aerobic training reduce the wall/lumen ratio (RW/L) of skeletal muscle arterioles and reduce mean arterial pressure (MAP) in hypertensive rats, cause bradycardia, and increase capillary and venular density also in hypertensive and normotensive rats after 13 weeks of training. We investigated simultaneously the time-course changes of arterioles remodeling, MAP, HR and capillary and venular density during the development of low-intensity exercise protocol. Normotensive rats (WKY, Wistar Kyoto) and spontaneously hypertensive (SHR), two-months old were submitted to aerobic training protocol (weeks 0, 1, 2, 4, 8 and 12) or remained sedentary (weeks 0 and 12). In each study time were measured the MAP and HR and collected heart, kidney, temporalis, soleus and gastrocnemius muscles to analyze the RW/L and quantificate capillaries and venules (by Periodic Acid-Schiff staining). Aerobic training increased capillary and venular density of WKY and SHR (only in exercised territories), caused a reduction of the RW/L of skeletal muscle arterioles (only in SHR, early and in greater magnitude in exercised territories) and only then reduced MAP of SHR and HR of WKY and SHR. The structural changes of microcirculation preceded improvement of blood pressure levels in hypertensive rats and provided vascular improvements to normotensive rats

Durante a vida intrauterina, o desenvolvimento do embrião e do feto é suscetível a mudanças ambientais que podem alterar o fenótipo do indivíduo na vida pós-natal. Eventos que ocorrem durante períodos críticos de rápida divisão celular, nos quais são formados os diversos órgãos e tecidos, podem alterar a estrutura e função de sistemas orgânicos gerando consequências precoces (baixo peso ao nascimento) e tardias (doenças na vida adulta). Os protocolos experimentais da maior parte dos estudos sobre a programação fetal reduz o tamanho da ninhada logo após o nascimento. Essa abordagem dificulta a interpretação e reprodutibilidade dos resultados observados. O objetivo deste estudo foi determinar se a pressão sanguínea, o metabolismo de carboidratos e gasto energético em proles adultas é influenciado pelo tamanho da ninhada. Ratas Wistar foram alimentadas com ração padrão ad libitum e foram acasaladas com ratos machos com 12 semanas de idade. Após o nascimento, a prole foi dividida em três grupos: tamanho da ninhada sem redução (Gc), proles reduzido a oito filhotes (G8) e proles reduzidos a quatro filhotes (G4). Ao fim de 12 semanas de idade, o peso corporal, pressão arterial, consumo de ração, glicemia, insulina, colesterol e triacilgliceróis, massa de tecido adiposo marrom, índice de adiposidade, massa renal e cardíaca foram determinados. O peso corporal, índice de adiposidade, glicemia, nível de insulina e índice HOMA foram maiores em machos e fêmeas no grupo G4 do que nos grupos G8 e Gc. No entanto, o consumo de ração foi menor no grupo G4. A pressão arterial foi maior no grupo Gc em machos e fêmeas. Em resumo, a redução do tamanho da ninhada está relacionada com a obesidade, resistência à insulina e possíveis alterações no gasto energético na prole adulta / During intrauterine life, the developing fetus is susceptible to environmental changes that can alter the phenotype of the individual in postnatal life. This phenomenon is called fetal programming. Events that occur during critical periods of rapid cell division may alter the structure and function of organ systems, resulting in consequences both early (low birth weight) and late (diseases in adulthood) in life. The experimental protocols of most of the studies on fetal programming involve a reduction in litter size soon after birth. This approach hampers the interpretation and reproducibility of the observed results. The purpose of this investigation was to determine if blood pressure, carbohydrate metabolism and energy expenditure in adult offspring are influenced by litter size. Female Wistar rats were fed standard rat chow ad libitum and were mated with male rats at 12 weeks of age. After birth, the offspring were divided into three groups: unchanged litter size (GU), culled to eight neonates (G8) and culled to four neonates (G4). At 12 weeks of age, the body weight; blood pressure; food intake; glucose, insulin, cholesterol and triacylglycerol levels; brown adipose tissue mass; adiposity index; renal mass; and cardiac mass were determined. The body weight, adiposity index, glucose level, insulin level and HOMA index were higher in males and females in the G4 group than in the G8 and GU groups. However, food consumption was lower in G4 males. The blood pressure was higher in the GU group. In summary, a small litter size is related to obesity, possible alterations in energy expenditure and insulin resistance in adult offspring

INTRODUÇÃO: O treinamento físico é uma intervenção eficaz para reduzir a pressão arterial (PA) na hipertensão, mas ainda há pouca evidência na literatura sobre os efeitos do treinamento físico em piscina aquecida. Este estudo examina os efeitos do treinamento em piscina aquecida sobre a PA, bem como sobre as respostas neuro-humorais e endoteliais em pacientes hipertensos resistentes. MÉTODOS: Trata-se de um estudo paralelo, randomizado e controlado. Foram investigados 44 pacientes sedentários com hipertensão resistente, randomizados e alocados em dois grupos; 28 pacientes foram submetidos à um protocolo de treinamento, que consistiu de exercícios calistênicos e caminhada dentro de uma piscina aquecida (32°C), realizados por uma hora, três vezes por semana durante doze semanas; e 16 pacientes foram alocados no grupo controle, esses foram orientados a manter suas atividades habituais. As medições feitas antes e após doze semanas do protocolo incluíram: PA de consultório, monitorização ambulatorial da pressão arterial (MAPA), níveis plasmáticos de óxido nítrico, endotelina-1, aldosterona, renina, noradrenalina, adrenalina e dopamina, assim como VO2 pico e função endotelial (hiperemia reativa). RESULTADOS: Após doze semanas, os pacientes do grupo treinamento apresentaram diminuição significativa na PA de consultório (Sistólica de 164,2 ± 3,3 para 128,9 ± 1,9 mmHg e Diastólica de 89,3 ± 1,7 para 78,0 ± 1,6 mmHg (P < 0,01) e na MAPA de 24 horas (Sistólica de 144,8 ± 3,8 para 126,4 ± 2,3 mmHg, Diastólica de 83,8 ± 2,1 para 74,8 ± 1,6 mmHg (P < 0,01), Vigília (Sistólica de 149,0 ± 4,0 para 129,0 ± 2,4 mmHg, Diastólica de 86,9 ± 2,2 para 75,6 ± 1,7 mmHg (P < 0,01); Sono (Sistólica de 136,1 ± 3,6 mmHg para 115,9 ± 1,8 mmHg, Diastólica de 75,9 ± 2,0 para 70,1 ± 1,6 mmHg (P < 0,01). Concomitantemente, o óxido nítrico aumentou significativamente (de 25±2,8 para 75±2,4 ?mol/L (P < 0,01), enquanto a endotelina-1 (de 41 ± 5 para 26 ± 3 pg / mL), a renina (de 35 ± 4 para 3,4 ± 1 ng / mL / h) , a noradrenalina (de 720 ± 54 para 306 ± 35pg / mL), a adrenalina (353,1 ± 4,1 para 169± 2,2 ng/mL) e dopamina ( de 145,1 ± 2,2 para 36,3 ± 3,1 ng/mL) diminuíram significativamente (P < 0,01). A aldosterona plasmática também tendeu a diminuir, embora não significativamente (de 101 ± 9 para 76 ± 4 pg / mL, P = NS). O VO2 pico aumentou, significativamente, após o treinamento (P < 0,01), enquanto a função endotelial permaneceu inalterada, e não foram encontradas alterações significativas no grupo controle. CONCLUSÕES: O treinamento em piscina aquecida reduziu os níveis de PA tanto ambulatorial quanto durante a MAPA de 24 horas em pacientes hipertensos resistentes e esta resposta da PA foi acompanhada por uma redução significativa da acentuada ativação neurohumoral, que caracteriza essa condição clínica. Estes efeitos sugerem que o treinamento em piscina aquecida pode ser uma potencial nova abordagem terapêutica para estes pacientes / BACKGROUND: Regular exercise is an effective intervention to decrease blood pressure (BP) in hypertension, but no data is available concerning the effects of Heated water-based Exercise (HEx). This study examines the effects of HEx on BP as well as on the neurohumoral and endothelial responses in resistant hypertensive patients. METHODS: This is a parallel, randomized controlled trial. We investigated 44 sedentary patients with resistant hypertension, they were randomized and allocated into 2 groups; 28 patients to a HEx training protocol, which was consisted of callisthenic exercises and walking inside a heated pool (32°C), performed for 1 hour, three times a week for 12 weeks; and 16 patients who were allocated on the control group were asked to maintain their habitual activities. The measurements made before and after 12 weeks of the protocol included clinic BP, ambulatory blood pressure monitoring (ABPM), plasma levels of nitric oxide, endothelin-1, aldosterone, renin, norepinephrine, epinephrine and dopamine, as well as peak VO2, and endothelial function (reactive hyperemia). RESULTS: After 12 weeks of HEx, patients showed a significant decrease in clinic BP (SBP from 164.2 ± 3.3 to 128.9 ± 1.9 mmHg; and DBP from 89.3 ± 1.7 to 78.0 ± 1.6 mmHg (P < 0.01); and on 24-h ABPM (24-h (SBP from 144.8 ± 3.8 to 126.4 ± 2.3 mmHg, DBP from 83.8 ± 2.1 to 74.8± 1.6 mmHg (P < 0.01); Daytime (SBP from 149.0 ± 4.0 to 129.0± 2.4 mmHg, DBP from 86.9 ± 2.2 to 75.6 ± 1.7 mmHg (P < 0.01); Nightime (SBP from 136.1± 3.6 mmHg to 115.9 ± 1.8 mmHg, DBP from 75.9 ± 2.0 to 70.1 ± 1.6 mmHg (P < 0.01). Concomitantly, nitric oxide increased significantly (from 25±2,8 to 75±2,4 ?mol/L, P < 0.01), while endothelin-1 (from 41±5 to 26±3 pg/mL), renin (from 35±4 to 3.4±1 ng/mL/h), norepinephrine (from 720±54 to 306±35pg/mL), epinephrine ( from 353,1 ± 4,1 to 169 ± 2,2 ng/mL) and dopamine (from 145,1 ± 2,2 to 36,3 ± 3.1 ng/mL decreased significantly (P < 0.01). Plasma aldosterone also tended to decrease, although not significantly (from 101±9 to 76±4 pg/mL, P=NS). Peak VO2 increased significantly after HEx (P < 0.01), while endothelial function was unchanged. No significant change was detected in the control group. CONCLUSIONS: HEx reduced office BPs and 24-hour ABPM levels in resistant hypertensive patients and this BP response was accompanied by a significant reduction in the marked neurohumoral activation characterized in this clinical condition. These effects suggest that HEx may be a potential new therapeutic approach in these patients

Introdução: A apneia obstrutiva do sono (AOS) é uma condição clínica comum associada com o aumento do risco cardiovascular. No entanto, a maioria dos estudos envolvendo AOS e desfechos cardiovasculares recrutaram de forma preponderante os homens. Em pacientes hipertensos, a AOS pode contribuir para a lesão de órgãos-alvo e alterações no descenso noturno em homens. O impacto da AOS nas mulheres hipertensas é pouco estudado. O objetivo deste estudo é estudar o impacto da AOS na rigidez arterial da aorta (avaliada pela velocidade da onda de pulso, VOP, carótida-femoral), disfunção diastólica e alterações do descenso noturno da pressão arterial em ambos os gêneros. Fazemos a hipótese de que a AOS está associada com alterações na rigidez arterial, disfunção diastólica e comportamento da pressão arterial independente do gênero. Métodos: Recrutamos de forma consecutiva pacientes hipertensos estágio 2 do ambulatório de Hipertensão do Instituto do Coração. Padronizamos a medicação anti-hipertensiva (hidroclorotiazida 25mg ao dia e enalapril 20mg 2x ao dia ou losartan 50mg 2x ao dia em caso de intolerância ao enalapril) por 1 mês. A adesão do tratamento aconteceu por meio da contagem de pílulas. Foram realizadas avaliações da monitorização ambulatorial da pressão arterial (MAPA), VOP, ecocardiograma transtorácico, exames laboratoriais e a Polissonografia Noturna. A AOS foi diagnosticada por um índice de apneia e hipopneia >= 15 eventos por hora de sono. Resultados: Foram inicialmente recrutados 125 participantes e após as exclusões, avaliamos 95 pacientes hipertensos (56% mulheres). A frequência da AOS foi de 66,7% em homens e 45,3% em mulheres (p=0,02). Em relação às mulheres sem AOS, mulheres com AOS eram mais velhas, tinham maior índice de massa corpórea e apresentaram maiores circunferências cervical e abdominal. Os homens com e sem a AOS foram semelhantes em várias características, exceto por uma circunferência abdominal maior no grupo com AOS. Comparado aos pacientes sem AOS, a VOP foi estatisticamente maior nos homens portadores de AOS (11,1±2,2 vs. 12,7±2,4m/s, respectivamente; p=0,04), assim como nas mulheres (11,8±2,4 vs. 13,2±2,2m/s, respectivamente; p=0,03). Em relação à disfunção diastólica, apenas as mulheres com AOS mostraram maior porcentagem dessa alteração ecocardiográfica (46,1 vs. 81,8%, respectivamente; p=0,007). Foi visto nos resultados da MAPA, que homens com AOS apresentaram menor frequência do descenso noturno sistólico (46,4 vs. 14,3%, respectivamente; p=0,04) e as mulheres, uma tendência (65,2 vs. 41,4%; p=0,07). O resultado da regressão linear mostrou que a presença de AOS promove aumento independente nos valores da VOP. O resultado da regressão logística evidenciou que a presença da AOS não foi associada com a disfunção diastólica, mas foi com a ausência do descenso noturno do componente sistólico da pressão arterial. Conclusões: Em pacientes hipertensos, a presença da AOS foi associada com um aumento na rigidez arterial independente do sexo, assim como a ausência do descenso noturno do componente sistólico da pressão arterial. Estes dados sugerem que mulheres hipertensas também estão expostas às consequências vasculares da AOS / Introduction: Obstructive sleep apnea (OSA) is a common condition associated with increased cardiovascular risk. However, most of studies that addressed OSA and its cardiovascular consequences enrolled mainly men. In hypertensive patients, OSA may contribute to increased target organ damage and alterations in the blood pressure dipping in males. However, the impact of OSA in hypertensive females is not well established. In this study, we compared the impact of OSA on arterial stiffness of the aorta (evaluated by carotid-femoral pulse wave velocity, PWV), as well as diastolic dysfunction and blood pressure dipping in men and women with hypertension. We made the hypothesis that OSA is associated with higher arterial stiffness, higher frequency of diastolic dysfunction and impaired blood pressure behavior regardless of gender. Methods: We recruited consecutives stage 2 hypertensive patients from the outpatient clinic at the Heart Institute. We performed a 30-day standardized anti-hypertensive treatment with hydrochlorothiazide 25mg per day plus enalapril 20mg BID or losartan 50mg BID (if enalapril intolerance). Adherence to treatment was confirmed through pill counting. After that, all volunteers were submitted to clinical evaluation, carotid-femoral PWV, 24-hour ambulatory blood pressure monitoring, transthoracic echocardiogram, and polysomnography. OSA was defined by an apnea-hypopnea index >= 15 events per hour. Results: We initially recruited 125 participants and after exclusions ninety-five patients were studied (56% women). OSA was present in 52 patients (men: 66.7%; women: 45.3%; p=0.02). In comparison to women without OSA, women with OSA were older, had higher body mass index and higher neck and abdominal circumferences. In men, there were no differences between OSA and no-OSA groups, except for higher values of abdominal circumference in OSA patients. Compared to no-OSA patients, PWV values were higher in the OSA group among both males (11.1±2.2 vs. 12.7±2.4m/s, respectively; p=0.04) and females (11.8±2.4 vs. 13.2±2.2m/s, respectively; p=0.03). The impact of OSA on diastolic dysfunction was significant only in females (46.1 vs. 81.8%, respectively; p=0.007). Regarding ambulatory blood pressure monitoring data, the frequency of systolic blood pressure dipping was significantly lower in men with OSA (46.4 vs. 14.3%, respectively; p=0.04) and marginal but non-significant in women (65.2 vs. 41.4%; p=0.07). Linear regression analysis showed that the presence of OSA was independently associated with higher PWV. In the logistic regression analysis, OSA was not associated with diastolic dysfunction but independently associated with nondipping systolic blood pressure. Conclusion: In patients with hypertension, OSA has significant associated with higher arterial stiffness and nondipping systolic blood pressure regardless of gender. These data suggest that hypertensive women are also exposed to the vascular and hemodynamic consequences of OSA

As doenças cardiovasculares são a maior causa de morte no mundo e entre essas doenças, a hipertrofia cardíaca (HC) tem se destacado especialmente por ser um fator de risco de insuficiência cardíaca. A HC é um fenômeno que acompanha a hipertensão arterial e no qual se observa aumento de proteínas estruturais e contráteis dos cardiomiócitos, havendo muitas vezes concomitantemente aumento do colágeno intersticial. Fatores independentes da pressão arterial também podem contribuir para o desenvolvimento da hipertrofia cardíaca. Dentre estes fatores, a sobrecarga de sal na dieta tem se destacado. Diversos estudos comprovam o efeito hipertrófico do sal. Em modelos animais onde se estudou sobrecarga de sal, não foi detectado aumento da atividade de renina plasmática, sugerindo que o sistema renina-angiotensina aldosterona (SRA) circulante pode não estar envolvido no desenvolvimento da hipertrofia cardíaca. Apesar de alguns estudos tentarem elucidar o papel do sal no desenvolvimento da hipertrofia ventricular esquerda, os mecanismos pelo qual o sal atua ainda não estão totalmente esclarecidos. Neste contexto, o objetivo do presente estudo é observar os fenômenos que ocorrem no ventrículo esquerdo em resposta a sobrecarga de sal na dieta na tentativa de elucidar sua fisiopatologia. Para tanto, ratos Wistar machos foram divididos em cinco grupos de acordo com a dieta (normossódica 1,26% e hipersódica 8% de NaCl) e com o tratamento (losartan, cloridrato de hidralazina ou N-acetilcisteína). Foi avaliada a evolução ponderal, pressão arterial caudal, medida do diâmetro transverso do cardiomiócito, fibrose intersticial, expressão gênica e proteica dos componentes do SRA, dosagem de aldosterona sérica e cardíaca, dosagem de TBARS cardíaco, concentração de angiotensina II e estado conformacional dos receptores AT1 e AT2. Os principais resultados observados foram: o aumento do consumo de ração (com elevada concentração de NaCl) do grupo HS+NAC e consequente aumento na pressão arterial e peso corpóreo; o desenvolvimento de HC independente do incremento da pressão arterial no grupo HS+HZ e a prevenção total ou parcial dessa hipertrofia através dos tratamentos com losartan e N-acetilcisteína, respectivamente e prevenção da fibrose intersticial nos grupos tratados com hidralazina, losartan e N-acetilcisteína / Cardiovascular diseases are the leading cause of death worldwide and among these diseases, the cardiac hypertrophy (CH) has been highlighted, especially as an important risk factor for developing heart failure. The CH is a phenomenon that accompanies hypertension and in which there is increased structural and contractile proteins in cardiomyocytes, with often concomitant increase of interstitial collagen. Blood pressure independent risk factors can also contribute to the development of cardiac hypertrophy. Among these factors, the high salt intake has been outstanding. Several studies confirm the hypertrophic effect of salt. In animal models submitted to salt overload, no increase in plasma renin activity was observed, suggesting that the renin-angiotensin (RAS) circulating system may not be involved in the development of cardiac hypertrophy. Although some studies attempting to elucidate the role of salt in the development of left ventricular hypertrophy, the mechanisms by which salt acts are not yet fully understood. In this context, the objective of this study is to observe the phenomena occurring in the left ventricle in response to dietary salt overload in an attempt to elucidate its pathophysiology.Male Wistar rats were divided into five groups according to their diet (1.26% and 8% NaCl) and treatment (losartan, hydralazine or N-acetylcysteine). We evaluated the body weight, tail-cuff blood pressure, the transverse diameter of the cardiomyocyte, interstitial fibrosis, gene and protein expression of RAAS components, serum and cardiac aldosterone dosage, cardiac TBARS, angiotensin II concentration and binding of conformation-specific anti-AT1 and anti-AT2 antibodies. The main results were: increased food intake (with high NaCl content) in the HS + NAC group and consequent increase in blood pressure and body weight; developing blood pressure-independent CH in the HS + HZ group partial or total prevention of such hypertrophy by treatment with losartan and N-acetylcysteine, respectively, and prevention of interstitial fibrosis in groups treated with hydralazine, losartan and N-acetylcysteine

<p>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 naru&scaron;enim dnevno-noćnim ritmom arterijskog krvnog pritiska takođe je činilo 90 ispitanika. U svakoj od ovih grupa izvr&scaron;ena 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 vi&scaron;e 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 če&scaron;će (p=0,011) uočava kod onih ispitanika koji nemaju očuvan dnevno-noćni ritam arterijskog krvnog pritiska. Naru&scaron;en dnevno-noćni ritam arterijskog krvnog pritiska takođe dovodi do povećanja indeksirane mase miokarda leve komore prema povr&scaron;ini tela ispitanika (LVM/BSA) &ndash; p=0,001; do zadebljanja zidova leve komore (IVS/PLW) &ndash; p=0,025, kao i do smanjenja sistolne brzine miokarda na nivou septalnog dela mitralnog anulusa (s&rsquo;) - p&lt;0,0005. Pored ovoga, u grupi onih sa naru&scaron;enim dnevno-noćnim ritmom arterijskog krvnog pritiska primećeno je če&scaron;će prisustvo ekscentrične hipertrofije miokarda leve komore (p=0,027). U odnosu na geometriju i funkciju leve pretkomore, naru&scaron;en 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) &ndash;p=0,007; indeksiranog LAVs prema povr&scaron;ini tela ispitanika (LAVs/BSA)-p&lt;,0005; E/e&rsquo; odnosa &ndash;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 če&scaron;će (p&lt;0,0005). Takođe, sa trajanjem arterijske hipertenzije statistički značajno se menjaju i parametri leve komore za koje smo pokazali da su pogor&scaron;ani kada dnevno-noćni ritam arterijskog krvnog pritiska nije očuvan, s tim &scaron;to smo ovde uočili i značajne promene u smislu postojanja lo&scaron;ijih vrednosti strain-a leve komore (LVGS)-p&lt;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 če&scaron;će (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&lt;0,0005): LA, LAVs, LAVs/BSA, E/e&rsquo;, 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.</p> / <p><!--[if gte mso 9]><xml> <o:DocumentProperties> <o:Author>Vukadin Milankov</o:Author> <o:Version>16.00</o:Version> </o:DocumentProperties> <o:OfficeDocumentSettings> <o:AllowPNG/> </o:OfficeDocumentSettings></xml><![endif]--><!--[if gte mso 9]><xml> <w:WordDocument> <w:View>Normal</w:View> <w:Zoom>0</w:Zoom> <w:TrackMoves/> <w:TrackFormatting/> <w:PunctuationKerning/> <w:ValidateAgainstSchemas/> <w:SaveIfXMLInvalid>false</w:SaveIfXMLInvalid> <w:IgnoreMixedContent>false</w:IgnoreMixedContent> <w:AlwaysShowPlaceholderText>false</w:AlwaysShowPlaceholderText> <w:DoNotPromoteQF/> <w:LidThemeOther>EN-US</w:LidThemeOther> <w:LidThemeAsian>X-NONE</w:LidThemeAsian> <w:LidThemeComplexScript>X-NONE</w:LidThemeComplexScript> <w:Compatibility> <w:BreakWrappedTables/> <w:SnapToGridInCell/> <w:WrapTextWithPunct/> 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Durante a vida intrauterina, o desenvolvimento do embrião e do feto é suscetível a mudanças ambientais que podem alterar o fenótipo do indivíduo na vida pós-natal. Eventos que ocorrem durante períodos críticos de rápida divisão celular, nos quais são formados os diversos órgãos e tecidos, podem alterar a estrutura e função de sistemas orgânicos gerando consequências precoces (baixo peso ao nascimento) e tardias (doenças na vida adulta). Os protocolos experimentais da maior parte dos estudos sobre a programação fetal reduz o tamanho da ninhada logo após o nascimento. Essa abordagem dificulta a interpretação e reprodutibilidade dos resultados observados. O objetivo deste estudo foi determinar se a pressão sanguínea, o metabolismo de carboidratos e gasto energético em proles adultas é influenciado pelo tamanho da ninhada. Ratas Wistar foram alimentadas com ração padrão ad libitum e foram acasaladas com ratos machos com 12 semanas de idade. Após o nascimento, a prole foi dividida em três grupos: tamanho da ninhada sem redução (Gc), proles reduzido a oito filhotes (G8) e proles reduzidos a quatro filhotes (G4). Ao fim de 12 semanas de idade, o peso corporal, pressão arterial, consumo de ração, glicemia, insulina, colesterol e triacilgliceróis, massa de tecido adiposo marrom, índice de adiposidade, massa renal e cardíaca foram determinados. O peso corporal, índice de adiposidade, glicemia, nível de insulina e índice HOMA foram maiores em machos e fêmeas no grupo G4 do que nos grupos G8 e Gc. No entanto, o consumo de ração foi menor no grupo G4. A pressão arterial foi maior no grupo Gc em machos e fêmeas. Em resumo, a redução do tamanho da ninhada está relacionada com a obesidade, resistência à insulina e possíveis alterações no gasto energético na prole adulta / During intrauterine life, the developing fetus is susceptible to environmental changes that can alter the phenotype of the individual in postnatal life. This phenomenon is called fetal programming. Events that occur during critical periods of rapid cell division may alter the structure and function of organ systems, resulting in consequences both early (low birth weight) and late (diseases in adulthood) in life. The experimental protocols of most of the studies on fetal programming involve a reduction in litter size soon after birth. This approach hampers the interpretation and reproducibility of the observed results. The purpose of this investigation was to determine if blood pressure, carbohydrate metabolism and energy expenditure in adult offspring are influenced by litter size. Female Wistar rats were fed standard rat chow ad libitum and were mated with male rats at 12 weeks of age. After birth, the offspring were divided into three groups: unchanged litter size (GU), culled to eight neonates (G8) and culled to four neonates (G4). At 12 weeks of age, the body weight; blood pressure; food intake; glucose, insulin, cholesterol and triacylglycerol levels; brown adipose tissue mass; adiposity index; renal mass; and cardiac mass were determined. The body weight, adiposity index, glucose level, insulin level and HOMA index were higher in males and females in the G4 group than in the G8 and GU groups. However, food consumption was lower in G4 males. The blood pressure was higher in the GU group. In summary, a small litter size is related to obesity, possible alterations in energy expenditure and insulin resistance in adult offspring

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Normal";mso-tstyle-rowband-size:0;mso-tstyle-colband-size:0;mso-style-noshow:yes;mso-style-priority:99;mso-style-qformat:yes;mso-style-parent:"";mso-padding-alt:0in 5.4pt 0in 5.4pt;mso-para-margin-top:0in;mso-para-margin-right:0in;mso-para-margin-bottom:10.0pt;mso-para-margin-left:0in;line-height:115%;mso-pagination:widow-orphan;font-size:11.0pt;font-family:"Calibri","sans-serif";mso-ascii-font-family:Calibri;mso-ascii-theme-font:minor-latin;mso-hansi-font-family:Calibri;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;}</style><![endif]-->Uvod: Traumatsko moždano o&scaron;tećenje (TMO) predstavlja globalni zdravstveni problem koji pogađa oko 10 miliona ljudi godi&scaron;nje &scaron;irom sveta. Te&scaron;ka traumatska moždana o&scaron;tećenja (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 op&scaron;te karakteristike ispitanika od značaja za istraživanje i sistemski prediktivni faktori (sistolni i srednji arterijski pritisak- SAP/MAP, glikemija-&Scaron;UK, 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 &bdquo;ishod lečenja&ldquo; 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 &bdquo;tok lečenja&ldquo; 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 izvr&scaron;ena pomoću statističkog paketa IBM SPSS 23. Podaci su predstavljeni tabelarno i grafički, a statistička značajnost određivana je na nivou p &lt; 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&lt;0,05). i vrednosti glikemije &gt; 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 &ndash; 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 &ndash; 4,091; p&lt;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, vi&scaron;a od 36,5 &deg;C veća je verovatnoća za bolji neurolo&scaron;ki oporavak, prilikom otpusta iz JIL, odnosno Klinike za neurohirurgiju KCV. Ispitanici koji su imali vi&scaron;e vrednosti telesne temperature su imali duže trajanje hospitalizacije (OR=4,096; 95%CI; 0,709-7,483;p&lt;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.</p> / <p>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 &quot;treatment outcome&quot; 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 &quot;treatment course&quot; 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 &lt;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&lt;0,05) and glycemic values &gt; 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 &ndash; 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 &ndash; 4,091;p&lt;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&deg; 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&lt;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.</p>