Orientador: Kleber Gomes Franchini / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-07T12:07:47Z (GMT). No. of bitstreams: 1 Borges_MariaCandidaCalzada_D.pdf: 3690302 bytes, checksum: 0c73a392de92a2836881cbe3034c49f5 (MD5) Previous issue date: 2006 / Resumo: Estudos epidemiológicos têm estabelecido uma relação contínua entre a massa do ventrículo esquerdo (VE) e o risco cardiovascular na população geral e na população hipertensa. O pior prognóstico de pacientes hipertensos com aumento na massa do VE tem sido, em parte, atribuído à disfunção do miocárdio, mas permanece desconhecido se os pacientes hipertensos sem hipertrofia do VE (HVE) definida pelos critérios habituais apresentam alterações na função do miocárdio. Os índices ecocardiográficos derivados das dimensões do VE e das velocidades do fluxo mitral aferidas através do Doppler têm provado ser geralmente não específicos e insensíveis para a detecção de alterações discretas da dinâmica ventricular. O Doppler Tecidual (DT) tem demonstrado ser um método eficiente e rápido para avaliar a função do miocárdio. Nos pacientes hipertensos com hipertrofia do VE tem sido descrita redução das velocidades sistólica e diastólica inicial. Entretanto não tem sido relatada investigação da função sistólica do miocárdio do VE através do DT em pacientes hipertensos sem ou com discreta elevação da massa do VE. O presente estudo avalia se, através da velocidade sistólica e diastólica aferidas pelo DT, é possível identificar alterações na contração e relaxamento do miocárdio de indivíduos hipertensos com ou sem hipertrofia ventricular definida pelos valores de corte habituais e com fração de ejeção preservada. Para tanto indivíduos normotensos e hipertensos com ou sem hipertrofia do ventrículo esquerdo (índice de massa do VE [IMVE] > 51g/m2.7) foram avaliados através da ecocardiografia convencional e do DT em 5 segmentos do anel mitral. Os subgrupos incluíram indivíduos normotensos não obesos (n=16; idade 51 ± 9 anos; 11 feminino; pressão arterial sistólica [PAS] 109 ± 11 mmHg; índice de massa corpórea [IMC] 24 ± 2,7 Kg/m2 ; IMVE 32 ± 5.5g/m2.7), hipertensos não obesos sem HVE (n=16; idade 54 ± 12 anos ; 12 femininos; PAS 166 ± 15 mmHg; IMC 25 ± 2,7 g/m2; IMVE 42 ± 5,5 g/m2.7) e hipertensos não obesos com HVE (n=22; idade 56 ± 10 anos; 10 feminino; PAS 181 ± 19 mmHg; IMC 26 ± 2,3 g/m2; IMVE 69 ± 16 g/m2.7). A fração de ejeção foi comparável entre os subgrupos, mas a fração de encurtamento da parede média foi reduzida nos pacientes hipertensos com hipertrofia do VE (¿26%). O tempo de relaxamento isovolumétrico foi aumentado nos pacientes hipertensos com hipertrofia do VE, enquanto a velocidade A do fluxo mitral encontrou-se aumentada em indivíduos hipertensos com e sem hipertrofia do VE. A velocidade sistólica (SM) e diastólica inicial (EM) aferida através do DT ao nível do anel mitral encontraram-se significativamente reduzidas nos indivíduos hipertensos com e sem HVE quando comparadas com as dos indivíduos normotensos. Evidenciou-se correlação positiva entre SM e EM (r=0,68; p<0,0001) e correlação negativa entre essas duas variáveis e o IMVE (SM, r= -0,41; p=0,002; EM, r= -0,56; p<0,0001). Portanto a redução na velocidade sistólica e diastólica ao nível do anel mitral acompanha o aumento da massa do VE em indivíduos hipertensos, iniciando-se em níveis de IMVE que se encontram abaixo dos valores definidos clinicamente como normais / Abstract: Epidemiological studies have established a continuous relationship between the left ventricular (LV) mass and cardiovascular risk in the general and hypertensive population. The poorer prognosis of hypertensive subjects with major increases in LV mass has been, in part, attributed to myocardial dysfunction, but it remains unknown whether hypertensive subjects without clinically defined LV hypertrophy have subtle abnormalities of myocardial function. Echocardiographic indices derived from LV chamber dimensions and Doppler measurements of flow velocities have been proved to be generally nonspecific and insensitive for the detection of minor abnormalities of cardiac relaxation and contraction. Tissue Doppler imaging (TDI) has been advocated as a reliable, rapid, and efficient method to assess myocardial function. In hypertensive patients with LV hypertrophy, TDI mitral annulus systolic and diastolic velocities have been shown to be reduced. However, a comprehensive TDI approach has not been reported in hypertensive subjects without or with minor increases in LV mass. The present study examines whether, by using TDI early systolic and diastolic velocities, one might identify changes in LV myocardial contraction and relaxation in subsets of hypertensive with and without clear-cut, clinically defined LV hypertrophy and normal LV ejection fraction. Normotensive and hypertensive subjects with and without left ventricular (LV) hypertrophy (LV mass index [LVMI] =51 g/m2.7) were examined by conventional echocardiography and tissue Doppler imaging of mitral annulus motion. The subgroups included non obese normotensive subjects (n=16; age 51±9 years; 11 female; systolic blood pressure [SBP] 109±11 mm Hg, body mass index [BMI] 24±2.7 kg/m2; LVMI 32±5.5 g/m2.7), non obese hypertensive subjects without LV hypertrophy (n=16; age 54±12 years; 12 female; SBP 166±15 mm Hg; BMI 25±2.7 kg/m2; LVMI 42_5.5 g/m2.7), and hypertensive subjects with LV hypertrophy (n=22; age 56±10 years; 10 female; SBP 181±19 mm Hg; BMI 26±2.3 kg/m2; LVMI 69±16 g/m2.7). Ejection fraction was comparable among the subgroups, but midwall fractional shortening was reduced in hypertensive subjects with LV hypertrophy (¿26%). Isovolumic relaxation time was increased in subjects with LV hypertrophy, whereas mitral wave A velocity was increased in hypertensive subjects with and without LV hypertrophy. Tissue Doppler imaging mitral annulus systolic (SM) and diastolic (EM) velocities were reduced in subjects with and without LV hypertrophy compared with normotensive subjects. There was a positive correlation between SM and EM (r=0.68; P<0.0001) and negative correlations between these 2 variables and LVMI (SM, r= -0.41; P=0.002; EM, r=-0.56; P<0.0001). Thus, reductions in mitral annulus systolic and diastolic velocities parallel increases in LV mass in hypertensive subjects, beginning at LV mass within the clinically defined normal values / Doutorado / Medicina Experimental / Doutor em Fisiopatologia Medica

A simpatectomia é uma modalidade terapêutica ampla e consagrada há décadas para determinadas patologias. Recentemente, alguns trabalhos sugerem a aplicação de tal técnica no tratamento da insuficiência cardíaca. Contudo, seus efeitos fisiológicos cardíacos em modelos experimentais foram pouco estudados. O objetivo deste trabalho é avaliar os efeitos fisiológicos da simpatectomia no coração. Para tal, foi utilizado o modelo experimental de simpatectomia em ratos pela técnica de esclerose do gânglio estrelado por punção e injeção de álcool absoluto. O estudo avaliou cinco grupos: controle (15 animais), simpatectomia unilateral esquerda (15 animais), simpatectomia bilateral (31 animais), simpatectomia unilateral esquerda com atenolol (15 animais) e atenolol sem simpatectomia (15 animais). Foram avaliadas as variáveis relacionadas ao sistema nervoso autônomo, como propriedades cronotrópicas em repouso e ao esforço, modulação autonômica cardiovascular, catecolaminas miocárdicas e periféricas e receptores beta-adrenérgicos do miocárdio. Também foram analisados os efeitos na função ventricular e no tamanho do miócito. As variáveis propostas para análise foram obtidas por ECG de repouso, ecocardiograma, teste de esforço máximo, frequência cardíaca ao esforço e variabilidade da FC e da PAS avaliadas no domínio do tempo e da frequência. As informações do miocárdio quanto a receptores, catecolaminas miocárdicas, catecolaminas periféricas e tamanho dos miócitos foram obtidas por PCR, ELISA, HPLC e morfometria do miócito, respectivamente. Este estudo evidenciou que os animais do grupo bilateral apresentam maiores níveis de catecolaminas periféricas e, consequentemente, são mais taquicárdicos e hipertensos. Os achados sugerem a ativação, neste grupo, de uma via compensatória que pode ter efeitos deletérios / Sympathectomy is a therapeutic modality used to treat certain diseases during decades. Recently, some studies suggest the application of this technique in the treatment of heart failure. However, its physiological effects upon the heart have been slightly studied. The objective of this study was to evaluate the physiological effects of sympathectomy in the heart. For this purpose, we used the experimental model of sympathectomy in rats by stellate ganglion sclerosis technique starring puncture and absolute alcohol injection. The study evaluated five groups of wistar rats: control (15), left unilateral sympathectomy (15), bilateral sympathectomy (31), left unilateral sympathectomy with atenolol (15) and atenolol without sympathectomy (15). We assessed variables related to the autonomic nervous system, such as chronotropic properties at rest and stress, cardiovascular autonomic modulation, myocardial and peripheral catecholamines and beta-adrenergic receptors in the myocardium. As well, we studied the effects on ventricular function and myocyte size. The proposed variables for analysis were obtained by resting electrocardiogram, echocardiography, maximal exercise test, heart rate at exercise and heart rate and systolic blood pressure variability in the time and frequency domain. The myocardial receptors, myocardial and peripheral catecholamines and myocyte size were obtained by PCR, ELISA, HPLC and myocyte morphometry, respectively. This study showed that the animals in the bilateral group had higher levels of peripheral catecholamine and, consequently, a higher heart rate and blood pressure. These findings suggest the activation of a compensatory pathway in the sympathectomy group that may have deleterious effects

No description available.

During the last two decades, since the heart has become a direct target for various surgical procedures for the correction of several abnormalities, interest in understanding its basic regulatory mechanisms and performance has increased considerably. Many experiments have been devised to study cardiac performance, under different circumstances, as an isolated preparation or as an integrated part of a functioning system. The results derived from these investigations not only proved to be important conceptual tools in making many observed phenomena more readily comprehensible, but also provided us with valuable basic principles to treat cardiac patients before and after open heart operations. The purpose of this paper is to investigate the control of the function of the heart in dogs with the chest and pericardium open, and under strictly controlled conditions. In spite of all the work j done in this field, there still exists some degree of confusion regarding the relative importance of autoregulatory mechanisms and extrinsic factors governing cardiac performance. Without trying to take sides as to the priority of either of these mechanisms, we have made an effort to confine our interest mainly to the intrinsic autoregulation of the heart.

This dissertation focuses on the effect of breeding on the myocardium of stallions using cardiac troponin I (cTnI) as the preferred blood biomarker for detection of myocardial cell injury. Haematological, echocardiographic and heart rate (HR) parameters are also reported. Fourteen clinically healthy phantom-trained stallions were assessed. Cardiac troponin I concentration was determined pre-semen collection and at 4, 6, 12 and 24 hours following semen collection. Predictors that were measured included mean HR during each stage of semen collection, maximum HR, area under the curve for HR and fractional shortening (FS). Pre-semen collection cTnI concentrations were within reported reference ranges for all stallions. Following semen collection, cTnI concentration was significantly increased at 4 and 6 hours post-semen collection. Results also suggest that the HR of stallions peak during mounting of the phantom. Five stallions failed to show an expected increase in FS immediately post-semen collection. No association was identified between the measured predictors and increased cTnI concentration. This study concluded that cTnI concentration may increase in stallions following semen collection although the clinical significance of this observed increase in healthy stallions is unclear without histopathological evaluation of the myocardium. No conclusion regarding FS immediately post-semen collection could be drawn from results in this study. The research reported in this dissertation can serve as a reference for future studies investigating cTnI concentrations in stallions. / Dissertation (MSc)--University of Pretoria, 2010. / Companion Animal Clinical Studies / unrestricted

Cardiovascular diseases, particularly acute myocardial infarction, are one of the leading causes of death in developed countries. It is well known that adaptation to chronic intermittent hypobaric hypoxia (IHH) confers long-lasting cardiac protection against acute ischemia/reperfusion injury. Protein kinase C (PKC) appears to play a role in its cardioprotective mechanism since the administration of general PKC inhibitor completely abolished the improvement of ischemic tolerance in IHH hearts. However, the involvement of individual PKC isoforms remains unclear. Therefore, the primary aim of this study was to investigate the potential involvement of PKCδ and PKCε, the most prevalent PKC isoforms in rat heart, in the mechanism of IHH-induced cardioprotection. We showed that IHH up- regulated PKCδ protein in left ventricle, enhanced its phosphorylation on Ser643 and increased its co-localization with markers of mitochondrial and sarcolemmal membranes. PKCδ subcellular redistribution induced by IHH as well as the infarct size-limiting effect of IHH was reversed by acute treatment with PKCδ inhibitor rottlerin. These data support the view that PKCδ plays a significant role in IHH-induced cardioprotection. On the other hand, adaptation to IHH decreased the PKCε total protein level without affecting its...

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in Europe. Over 4 million people die from CVDs annually and another 11 million people develops CVDs every year. These numbers show that there is a need for better diagnostic, prognostic and predictive biomarkers and, more importantly, a need for new and more efficient drugs. Integral membrane proteins (IMPs) are ideal candidates for new drug targets. However, a study of IMPs represents a major challenge in current proteomics. This challenge is associated with the low abundance of IMPs, their low solubility in aqueous solvents and the absence of trypsin cleavage sites in their transmembrane segments. To overcome these issues, methods that selectively target either N-glycosylated extra-membrane segments (CSC, SPEG, N-glyco-FASP) or transmembrane segments (hpTC) were developed. In this thesis we employed a combination of two N-glyco-capture methods (SPEG and N-glyco-FASP) performed on two different samples (membrane-enriched fraction and total tissue lysate) with analysis of membrane-embedded IMP segments by hpTC and with standard non-targeted "detergent+trypsin" approach to analyze rat myocardial membrane proteome. We also performed an evaluation of employed methods for preparation of membrane fraction by western blot...

The aim of present project was to uncover the effect of pharmacological increase in acute and chronic nitric oxide (NO) production on cardioprotective effect of chronic hypoxia. We studied the effect of NO donor molsidomine on hemodynamic conditions and ischemia - induced myocardium injury. Male Wistar rats were exposed to continual hypoxia in a normobaric chamber (10 % O2, 4 weeks). Rats received molsidomine either chronically (15 mg/kg/day) in drinking water or acutely (10 mg/kg) in saline infused 30 min before ischemia. Control rats were kept under normoxia and treated in a corresponding manner. Adaptation to chronic hypoxia resulted in development of pulmonary hypertension. Chronic treatment with molsidomine slightly reduced these consequences of chronic hypoxia but it had no effect on increased cardiac ischemic tolerance in chronically hypoxic rats. On the other hand acute treatment with molsidomine significantly reduced infarct size and increased the number of arrhythmias in both normoxic and chronically hypoxic animals. In conclusion, our data suggests that acute increase in availability of NO is cardioprotective in both normoxic and chronically hypoxic rats contrary to its chronic increase which seems to have no protective contribution.

The aim of the present study was to find out whether adaption to chronic hypoxia affects the expresion of TNF-α and IL-10 in rat myocardium. TNF-α is a proinflammatory cytokine, which amplifies inflammatory reaction, while IL-10 has opposite antiinflammatory effect. We also measured concentration of nitrotyrosine as a marker of nitrosative stress. We used male Wistar rats divided into four groups: 1) normoxic controls; 2) exposed to continous normobaric hypoxia (10% O2) for three days or 3) for three weeks and 4) exposed to intermittent normobaric hypoxia (10% O2) for three weeks with one hour daily reoxygenation. Cytosolic and membrane proteins (cytosolic and particulate fractions) were obtained from the left ventricle, right ventricle and interventricular septum. Concentrations of TNF-α and IL-10 in both fractions were measured by ELISA. Continous hypoxia increased TNF-α production in particulate fractions from all ventricular parts and decreased the ratio of IL-10/TNF-α in particulate and cytosolic fractions. Intermittent hypoxia redistributed TNF-α from cytosol into the particulate fraction and prevented the drop of IL-10/TNF-α ratio in the cytosolic fraction. The highest concentration of nitrotyrosine was found in the particulate fraction from the right ventricle after three days of hypoxia....

Morphine is a clinically very important drug from the opioid group that is used for treatment of severe pain because of its strong analgetic effect. Opioid receptors mediating the morphine effect interact with the Gi/o class of trimeric G-proteins. Opioid receptors also occur in heart tissue and morphine can thus potentially exercise its effect on the function of this organ. The major aim of this project was to pursue consequences of long-term treatment with morphine on expression and distribution of selected heterotrimeric G-protein subunits in the rat heart. Potential cardioprotective effects of this drug have also been studied. Laboratory rats of the Wistar strain were treated with morphine (1 mg/kg/day or 10 mg/kg/day) for 10 or 28 days. The control group was treated with saline solution. Prolonged treatment with morphine did not cause any effects on Gs, Gi, Gz, Gq/11, G subunits, but the expression of Go rather decreased. The results of subsequent experiments showed that prolonged administration of high doses of morphine may reduce the area affected by infarction and reduced the frequency of ventricle arrhythmias depending on dose and duration of morphine administration. Key words: morphine, myocardium, opioid receptor, G-protein subunits, infarction.