En pacientes con dolor torácico (DT) y sospecha de síndrome coronario sin elevación del ST (SCASEST), existe una necesidad clínica de diagnosticar el infarto agudo de miocardio (IAM) lo más precozmente posible, así como establecer de manera simple, económica y rápida su correcta estratificación de riesgo.El objetivo de la presente tesis doctoral fue analizar prospectivamente:1. El rendimiento diagnóstico en las primeras 24 horas de los diferentes marcadores de necrosis miocárdica (MNM) de acuerdo a la actual definición de IAM, así como analizar el rendimiento de un protocolo rápido (0-4 h.) para confirmar / excluir el IAM2. Predecir el riesgo de complicaciones cardiovasculares graves ( muerte / infarto no fatal) (CCV) a corto ( 30 días) y a largo plazo ( 1 año) de marcadores electrocardiográficos y bioquímicos aislados o conjuntamente.Se diseñó un estudio prospectivo, transversal y abierto, con reclutamiento continuo de pacientes durante 03-12 del 2000. 361 pacientes dieron su conformidad para el estudio.En todos los pacientes se realizó un ECG al ingreso y a las 4 horas de su admisión en el servicio de urgencias (SU). En todos los pacientes se determinó seriadamente durante las primeras 4 horas de su ingreso los siguientes MNM: creatin-cinasa total (CK), creatin-cinasa MB (CKMB), mioglobina (Miog) y troponina T cardíaca (TnT).En los pacientes hospitalizados, se realizó una determinación adicional de MNM a las 24 horas de su admisión.El análisis estadístico constó de descripción, análisis bivariante, estudio del rendimiento diagnóstico / pronóstico de las variables electrocardiográficas - biológicas y análisis multivariante de las variables predictoras de CCVLas principales conclusiones de la tesis fueron:1.- Si bien la mioglobina es el MNM más precoz y sensible, también es el menos específico de IAM. La TnT, reune la mejor combinación de sensibilidad (Se) y especificidad (Ep) independientemente del tiempo de evolución del IAM2.- Las determinaciones seriadas de TnT durante las primeras 4 h. del ingreso presentan una eficacia diagnóstica (Ef) de IAM del 97%, que no es mejorada por la adición de otros marcadores3.- La infradesnivelación del segmento ST del ECG ( ØST) es la alteración ECG con mejor rendimiento diagnóstico de IAM (Ef del 75%)4.- La ØST presenta el máximo valor predictivo positivo (VPP) de CCV a los 30 días y al año de seguimiento (21% y 42% respectivamente. P< 0,05)5.- Los criterios actualmente aceptados como definidores de IAM para TnT y CKMB son los mejores predictores bioquímicos de CCV, tanto si se utiliza su determinación inicial o las determinaciones globales en las primeras 4 horas del ingreso6.- La TnT > 0,04 mg/L ofrece la mejor capacidad predictiva de CCV a los 30 días y al año de evolución ( área ROC = 0,77). Esta capacidad predictiva se optimiza hasta 0,84 si se utiliza un valor de 0,05 mg/L7.- El valor pronóstico de la TnT aumenta con el nivel alcanzado en su concentración8.-La edad, la ØST y la TnT > 0,04 mg/L son las únicas variables independientes con predicción de riesgo de CCV9.- Utilizando las tres variables previamente mencionadas se puede estratificar el riesgo de CCV a corto y a largo plazo. / In patients with chest pain (CP) and suspected acute coronary syndrome without ST elevation (SCASEST), there is a clinical need to diagnose AMI as soon as possible, as well as establishing in a simple, economic and quick way its correct risk stratification.The aim of this doctoral thesis was to analyse prospectively:1. The diagnostic performance in the first 24 hours of the different MMN in agreement with the present definition of AMI, as well as a quick protocol to confirm or exclude AMI.2. To predict the risk of serious cardiovascular complications ( death/ non fatal AMI) (CVC) at short (30 days) and long term (1 year) with ECG and MMN isolated or in combination.A prospective, transversal and open study was designed with continuous recruitment of patients from March to December 2000. 361 patients agreed to take part in the study.An ECG was carried out on all patients on admission and 4 hours after admission in the emergency departement.In all patients the following MMN were measured during the first 4 hours after admission. Creatin-Kinase (CK), creatin -Kinase MB (MBCK), cardiac Troponin T (TnT) and myoglobine (Miog). In hospitalised patients and additional measurement of MMN, was carried 24 hours after admission.The statistics consisted of a descriptive, bivariate analysis of diagnostic- prognostic performance of ECG and MMN, and multivariate analysis of predictive variables of CVC.The main conclusions of this thesis have been:1.- While myoglobin is the earliest and sensitive (Se) MMN, it is also the least specific (Sp) of AMI. TnT, combines the best combination of Se and Sp at each of the time of the evolution of the AMI.2.- The consecutive determinations of TnT during the first 4 hours of admission gave a diagnostic efficiency (Ef) of AMI of 97%, which is not improved with the addition of other markers.3.- The ØST was the ECG abnormality with the best diagnostic performance (Ef of 75%)4.- The ØST presented the maximum VPP of CVC at 30 days and one year of follow-up ( 21% and 42% respectively. p < 0,05)5.- The current accepted criteria of AMI for TnT and CKMB are the best MMN predictors of CVC, whether these are used for the determination on admission or the global determinations during the first 4 hours after admission.6.- The TnT > 0,04 mg/L offers the best predictive capacity of CVC at 30 days and one year of evolution ( ROC area = 0,77). This predictive capacity is improved up to 0,84 if a cut-off of 0,05 mg/L is used7.- The prognostic value of TnT increases with the level reached in its concentration8.- Age, ØST and TnT > 0,04 mg/L are the only independent variables able to predict CVC.9.- Using the three previously mentioned variables we can stratify the risk of CVC at short and long term.

El objetivo de este trabajo es estudiar la viabilidad de utilizar, en la práctica clínica, métodos de medida mínimamente invasivos y no invasivos para contribuir al diagnóstico del infarto de miocardio y del rechazo de transplante, a partir de la medida de espectroscopia de impedancia eléctrica (EIE) obteniendo un estimador cuantitativo que nos permita conocer el estado del tejido de miocardio.Para conseguir este objetivo, la tesis se ha dividido en tres fases dependiendo del grado de invasividad del método de medida empleado. La primera fase consistió en obtener las características eléctricas pasivas del tejido de miocardio, en tres estados: sano, isquemia aguda y cicatriz, a partir de medidas invasivas no transmurales, método a 4 electrodos con electrodos de aguja, y medidas invasivas transmurales, método a 3 electrodos con un catéter intracavitario. Estableciendo las diferencias entre cada estado del tejido de miocardio para cada uno de los métodos de medida. A partir de estas medidas, y conociendo que era viable utilizar un método transmural para diferenciar el estado del tejido de miocardio, pasamos a la segunda fase. En esta fase construimos un modelo 3D de elementos finitos (EF) de una sección del tórax, que nos predijera la magnitud de los cambios que se podían esperar debido a la presencia de una cicatriz o de una isquemia aguda, además del efecto de movimiento y desplazamiento del catéter dentro de la cavidad. Así mismo, establecer las especificaciones del equipo de medida a utilizar. Para validar las simulaciones se realizaron experimentos in vitro tanto con solución salina-agar y tejido de miocardio. Una aplicación en la práctica clínica fue realizar medidas de EIE en un grupo de pacientes sanos y otro grupo de pacientes con transplante de corazón, para establecer la viabilidad de la técnica en la detección del rechazo de transplante agudo. En la tercera fase, se ha utilizado el modelo 3D de EF del tórax para optimizar la posición de 4 electrodos superficiales para la detección de una isquemia aguda. El modelo se simuló con una inyección de corriente detección de tensión adyacente-adyacente para una configuración de 16 electrodos que permitiera obtener las matrices de transimpedancia correspondientes y aplicar un algoritmo de optimización.A partir de todos los resultados obtenidos, podemos establecer que las medidas de impedancia eléctrica, y principalmente su fase, es una herramienta que permite monitorizar eventos fisiológicos y caracterizar estados fisiopatológicos del tejido como la isquemia aguda, la cicatriz e incluso el rechazo en corazones transplantados. Esta caracterización es más fácil con medidas invasivas pero también es posible mediante medidas mínimamente invasivas utilizando catéteres intracavitarios siempre que se realice una calibración adecuada que permita reducir los artefactos presentes en las medidas. El estudio con modelos matemáticos de las técnicas no invasivas ha demostrado que, con cuatro electrodos superficiales, la caracterización del tejido con isquemia aguda requeriría unas prestaciones que no son factibles con la tecnología disponible actualmente. Por lo tanto, las líneas de trabajo futuro deben enfocarse en diseñar un sistema cuya resolución y precisión permita realizar medidas de caracterización y monitorización del estado del tejido de miocardio on line. Y de esta forma tener una técnica atractiva en el ambiente hospitalario para monitorizar el tejido en la evolución del infarto de miocardio, en los procesos de ablación y en las biopsias endomiocárdicas de transplante de corazón. / The aim of this work is to study the viability to use minimally invasive and non invasive measurement methods, in the clinical environment, to contribute to the diagnosis of myocardium infarct and transplant rejection. We have used electrical impedance spectroscopy (EIS) measurements in order to obtain a quantitative estimator to know the state of the myocardium tissue. In order to achieve this objective, the thesis has been divided in three phases depending on the degree of invasivity of the measurement method used.The first stage consists on obtaining the passive electrical characteristics of the myocardium tissue, in three states: healthy, acute ischemia and scar. The invasive measurements are non transmural and transmural. The non transmural measurements are done with the 4 electrode method using needle electrodes, and transmural measurements are done with the 3 electrode method using an intracavitary catheter. It has been established in this stage the differences between each tissue state of the myocardium and for each measurement method. The second stage started with the viability of the transmural method results of the first stage to differentiate the myocardium tissue state. In this stage we constructed a 3D finite element model of a thorax section. This model was used to predict the changes in magnitude that could be expected due to the presence of an acute ischemia or scar, including the effect of movement and displacement of the catheter within the cavity. Also, it has been established the specifications of the measuring equipment to use. In order to validate the simulations, in vitro experiments with saline solution-agar and myocardium tissue were made. It has been also done measurements in a group of healthy patients and another group of patients with heart transplant, in a clinical environment, to establish the viability of the technique in the detection of the rejection of acute transplant. In the third stage, the 3D thorax model has been used to optimize the position of 4 superficial electrodes for the detection of acute ischemia. The model was simulated with a current-injection and voltage-detection with the adjacent-adjacent technique, for a configuration of 16 electrodes that allowed to obtain the transimpedance matrices and to apply an optimization algorithm. From all the obtained results, we can establish that the measurements of electrical impedance, and mainly its phase angle, is an estimator for monitoring physiological events and to characterize physiopatological states of the tissue as acute ischemia, scar and even the rejection in transplanted hearts. This characterization is easier with invasive measurements but also it is possible by means of minimally invasive measurements using intracavitary catheters whenever a suitable calibration is made to reduce the artefacts present in the measurements. The study with mathematical models of the noninvasive techniques has demonstrated that, with four superficial electrodes, the characterization of the acute ischemia tissue would require performances that are not feasible with the technology available at this moment. Therefore, the lines of future work must focus on designing a system whose resolution and precision allows us to make measurements to characterize and monitor the myocardium tissue state on line. It would be possible to have an attractive technique, in the hospital environment, to monitor the evolution of the tissue in a myocardium infarct, in ablation processes and in endomyocardial biopsies of heart transplant.

La información respecto a la respuesta del corazón aislado de ratas hipertensas espontáneas (SHR) a la isquemia-reperfusión y a los mecanismos de protección descriptos para ratas normotensas [pre y postacondicionamiento isquémicos (PI y PCI, respectivamente) y farmacológicos], es escasa. Por lo tanto, la participación de la vía PI3K/Akt/GSK-3β y del poro de permeabilidad transitoria de la mitocondria (PPTM) en los mecanismos responsables de la muerte ó la sobrevida de los cardiomiocitos de SHR, no están debidamente aclarados. El objetivo general de este trabajo de tesis fue estudiar en corazones de SHR aislados y perfundidos con la técnica de Langendorff los efectos de la isquemia global (IG, 45 min)-reperfusión (R, 60 min), del PI y PCI y del tratamiento con ClLi e IMI (inhibidores de GSK-3β) sobre el tamaño del infarto, el daño oxidativo, la sensibilidad del PPTM al Ca2+, la liberación de citocromo c al citosol y la ultraestructura mitocondrial. El protocolo de IG-R produjo un tamaño del infarto de aproximadamente 50% del área de riesgo y daño oxidativo, evidenciado por un aumento de la peroxidación lipídica (TBARS), una disminución marcada del contenido de GSH y un aumento de la actividad de SODT y SODMn. El contenido de P-GSK-3β y P-Akt y la sensibilidad del PPTM al Ca2+ disminuyeron, mientras que la expresión de citocromo c en el citosol aumentó. La microscopia electrónica reveló que la mayor parte de las mitocondrias estaban dañadas, con edema y destrucción de sus crestas. Las intervenciones PI y PCI y el tratamiento con los inhibidores de GSK-3β protegieron a los corazones de SHR de los daños antes mencionados. Por lo tanto, en los corazones intervenidos y tratados se observó una disminución del tamaño del infarto y del daño oxidativo evidenciado por la disminución de la peroxidación lipídica (TBARS), preservación parcial del contenido de GSH y disminución de la actividad de SODT y SODMn. La expresión de P-GSK3β y de P-Akt y de la sensibilidad del PPTM al Ca2+ aumentó mientras que el contenido de citocromo c en el citosol disminuyó. Por microscopia electrónica fue posible encontrar en estos grupos la presencia de algunas mitocondrias con ultraestructura conservada. Los efectos beneficiosos del PI y PCI fueron anulados cuando la vía de señalización de PI3K/Akt fue inhibida con wortmanina. Las variables mencionadas retornaron a los valores observados en los corazones isquémicos no tratados. De las relaciones examinadas surge que: a- el tamaño del infarto es mayor cuando la peroxidación lipídica aumenta y el contenido de GSH disminuye. En estas condiciones la sensibilidad del PPTM al Ca2+ es menor. La situación opuesta se da en presencia de intervenciones cardiorpotectoras. Por lo tanto, en ellas el tamaño del infarto es menor cuando la peroxidación lipídica disminuye y el contenido de GSH aumenta. En estas condiciones la sensibilidad del PPTM al Ca2+ tiende a recuperarse. En base a los datos obtenidos se concluye que las alteraciones de la formación y/ó apertura del PPTM, participan y determinan la muerte ó la sobrevida celular en el corazón hipertrófico de SHR sometido a isquemia-reperfusión. Así, la disminución del tamaño del infarto obtenida con las intervenciones y/ó tratamientos utilizados fue el resultado de la disminución del daño oxidativo íntimamente asociada a la recuperación parcial de la integridad mitocondrial -menor apertura del PPTM- vía P-Akt/P-GSK-3β. Otro hallazgo interesante fue que la protección por el tratamiento con ClLi (fármaco ampliamente utilizado en psiquiatría) fue similar a la obtenida con las intervenciones de acondicionamiento isquémico (PI y PCI). Por lo tanto, esta droga podría ser una posible herramienta terapéutica para atenuar la injuria por isquemia y reperfusión. / Information regarding to the response to ischemia-reperfusion in isolated hearts from spontaneously hypertensive rats (SHR) as well as the effect of the protective mechanisms described in normotensive rats (ischemic and pharmacological pre and postconditioning, IP and IPC), is scarce. Therefore, the participation of PI3K/Akt/GSK-3β pathway and the mitochondrial permeability transition pore (mPTP) in the mechanisms responsible for cardiomyocyte death or survival are not properly clarified. The objective of this investigation was to study in isolated hearts from SHR the effects of global ischemia (GI, 45 min) and reperfusion (R, 60 min), and the actions of IP, IPC, treatments with LiCl and IMI (GSK-3β inhibitors) on infarct size, oxidative damage, mPTP Ca2+ sensitivity, cytochrome c release to the cytosol and mitochondrial ultrastructure. The protocol of GI-R produced an infarct size of approximately 50%, increased oxidative damage as evidenced by an increase of lipid peroxidation (TBARS), a decrease of GSH content and an increase of Total SOD and MnSOD activity. The content of P-GSK-3β and P-Akt and the mPTP Ca2+ sensitivity decreased while the expression of cytochrome c in the cytosol increased. Electron microscopy showed that most of the mitochondria were damaged, presenting edema and destruction of the cristae. IP, IPC and pharmacologic treatments with both GSK-3β inhibitors protected the hearts against reperfusion injury. Therefore, in the hearts treated we observed a smaller infarct size and reduced oxidative damage (decreased lipid peroxidation (TBARS), partial preservation of GSH and decreased Total SOD and MnSOD activity) compared to non-treated ischemic hearts. The P-GSK-3β and P-Akt expression and mPTP Ca2+ sensitivity increased while the cytosolic cytochrome c content decreased. By electron microscopy it was possible to find some mitochondria with normal ultrastructure. The beneficial effects of IP and IPC were canceled when the PI3K/Akt was inhibited with wortmannin. All the parameters examined returned to the values observed in non-treated ischemic hearts. Analyzing the relationships: Infarct size vs. TBARS and GSH, and mPTP Ca2+ sensitivity vs. Infarct size and TBARS, it arises that: the Infarct size increased when lipid peroxidation increased and GSH content decreased. Under these conditions the mPTP Ca2+ sensitivity decreased. The opposite situation occurs in the presence of the cardioprotective interventions. Therefore, the infarct size decreased when lipid peroxidation decreased and GSH content increased. Under these conditions the mPTP Ca2+ sensitivity tended to recover. Based on the data obtained, we suggest that the alterations of formation and/or opening of the mPTP participate and determine cell death or survival in the hypertrophic heart of SHR subjected to ischemia-reperfusion. Thus, the reduction in infarct size obtained with the ischemic interventions and /or treatments derived from the decreased oxidative damage intimately linked to a partial recovery of mitochondrial integrity- less mPTP opening- via P-Akt/P-GSK-3β. Another interesting finding was that the protection by the treatment with LiCl (drug widely used in psychiatry) was similar to that obtained with ischemic interventions (IP and IPC). Therefore, this drug emerges as a potential therapeutic tool in reducing the post-ischemic changes.

El propósito general del presente trabajo de Tesis Doctoral fue estudiar la participación de la ET-1 endógena en el desarrollo de HC inducida por Ang II así como las vías de señalización intracelular involucradas. En virtud de los antecedentes expuestos se elaboró la siguiente hipótesis: la HC patológica se produciría como resultado de la activación de un mecanismo autocrino/paracrino desencadenado por el estiramiento del miocardio y que involucra la liberación de Ang II y ET-1, el aumento de las ERO y la activación del NHE-1. La figura 8 muestra la secuencia propuesta de los eventos que se desencadenarían en los miocitos cardíacos adultos cuando son expuestos a Ang II y/o ET-1.

Made available in DSpace on 2014-06-11T19:23:31Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-28Bitstream added on 2014-06-13T19:29:40Z : No. of bitstreams: 1 000749048.pdf: 1237628 bytes, checksum: be3b98d2b93763097cb297cd0ce5e744 (MD5) / O diabetes mellitus (DM) está associado a diversas doenças vasculares e cardíacas. Nos últimos anos, aumentaram as evidências de que pacientes diabéticos são acometidos por uma forma de doença miocárdica denominada miocardiopatia diabética. O aumento na produção de espécies reativas de oxigênio (EROs), causado por alterações metabólicas induzidas pelo DM, é um dos principais mecanismos desencadeadores de alterações miocárdicas. A maior fonte de EROs no sistema cardiovascular está relacionada a atividade da família de enzimas da NADPH oxidase. Em relação ao DM, há evidências de que a elevação da glicose sérica, induzida por estreptozotocina em camundongos ou em pacientes diabéticos, causa aumento na atividade da NADPH oxidase nos vasos. Sendo o sistema NADPH oxidase o principal responsável por desequilíbrio no sistema de produção e eliminação de EROs, e também por estar envolvido em muitas patologias cardíacas, estudos à respeito de seu bloqueio têm aumentado nos últimos anos. O objetivo do presente trabalho foi analisar a influência da inibição da NADPH oxidase por apocinina sobre o remodelamento cardíaco de ratos com DM. Foram utilizados ratos Wistar machos com 6 meses de idade, divididos em 4 grupos: controle (CTL, n=15), controle+apocinina (CTL+APO, n=20), diabético (DM, n=20) e diabético+apocinina (DM+APO, n=20). O diabetes foi induzido por estreptozotocina. Após 7 dias, foi iniciado tratamento com apocinina e mantido por 8 semanas. A avaliação estrutural e funcional in vivo do coração foi realizada por ecocardiograma. O estudo funcional in vitro foi realizado em músculo papilar isolado do ventrículo esquerdo (VE) em condições basal e após estimulação com manobras inotrópicas (contração pós-pausa, aumento da concentração extracelular de cálcio e adição de isoproterenol à solução nutriente). Para análise de variáveis anatômicas foram medidos os pesos úmidos... / Diabetes mellitus (DM) is associated with cardiac and vascular diseases. In recent years, there has been increased evidence that diabetic patients are affected by a form of myocardial disease known as diabetic cardiomyopathy. High production of reactive oxygen species (ROS), caused by diabetes-induced metabolic changes, is one of the main mechanisms leading to myocardial damage. A major source of ROS in the cardiovascular system is related to the activity of NADPH oxidase enzymes family. In streptozotocin-induced diabetic mice or in diabetic patients, serum glucose elevation increases NADPH oxidase activity in vessels. As NADPH oxidase is involved in imbalance of ROS production and elimination systems, and in pathophysiology of cardiac diseases, research on its blockade has increased in recent years. The purpose of this study was to analyze the influence of NADPH oxidase inhibition by apocynin on cardiac remodeling in rats with DM. Six month old male Wistar rats were assigned into 4 groups: control (CTL, n=15), control+apocynin (CTL+APO, n=20), diabetic (DM, n=20) and diabetic+apocynin (DM+APO, n=20). Diabetes was induced by streptozotocin. Seven days later, apocynin was initiated and maintained for 8 weeks. In vivo cardiac structures and functions were assessed by echocardiography. In vitro left ventricular (LV) functional study was performed in isolated papillary muscle preparation at basal condition and after inotropic stimulation with post-rest contraction, increase of extracellular calcium concentration, and addition of isoproterenol to the nutrient solution. Wet and dry weights of LV, right ventricle (RV), atria, lung, and liver sample were measured. LV histological sections were used to analyze interstitial collagen fraction. Antioxidant enzymes glutathione peroxidase (GSH-Px), catalase, and superoxide dismutase (SOD) were measured in serum. LV tissue samples were obtained for determination of ...

Made available in DSpace on 2014-06-11T19:23:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2009-02-17Bitstream added on 2014-06-13T18:50:43Z : No. of bitstreams: 1 gimenes_c_me_botfm.pdf: 464422 bytes, checksum: 627314a0c5f4867528442a8ec3866145 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A cirurgia de revascularização miocárdica (RM) envolve a cavidade torácica e, conseqüentemente, as complicações pulmonares são freqüentemente observadas. Fatores pré e intra-operatórios, como idade avançada, doença pulmonar, tabagismo, circulação extracorpórea (CEC), esternotomia, entre outros, contribuem para o prejuízo da função pulmonar. No período pós-operatório o paciente está predisposto a apresentar atelectasias e infecções respiratórias. Além disso, ocorrem alterações na mecânica respiratória, com diminuição da força dos músculos respiratórios e do pico de fluxo expiratório. Relacionar as variáveis clínicas e laboratoriais pré e intra-operatórias com o grau de redução das pressões respiratórias máximas e do pico de fluxo expiratório em pacientes submetidos à cirurgia de RM. Foram estudados 61 pacientes que foram submetidos à cirurgia de RM, sob CEC, esternotomia mediana, e mantidos em ventilação mecânica por período máximo de 24 horas. No dia anterior à cirurgia, foram realizadas entrevista, consulta ao prontuário, e avaliação das pressões respiratórias (pressões inspiratória e expiratória máximas, PImáx e PEmáx), por meio da manovacuometria e medida do pico de fluxo expiratório (PFE). No 5° dia de pósoperatório, foram repetidas as medidas de PImáx, PEmáx e PFE. A análise estatística foi realizada por meio de teste t de Student, correlação linear de Pearson e modelo de regressão logística. Os resultados são discutidos no nível de significância de 5%. Características gerais: idade, 63±10 anos; sexo masculino, 67%; IMC, 28,0±3,8 Kg/m2; hemoglobina (Hb), 12,8±1,7 g/dl; prevalência de: infarto prévio 67%, hipertensão arterial sistêmica 75%, diabetes mellitus 31%, Resumo 57... / The coronary artery bypass grafting (CABG) affects the thoracic cavity and consequently pulmonary complications are frequently observed. Preand intra-operative factors as advanced age, pulmonary disease, smoking, cardiopulmonary bypass (CPB), sternotomy, among others, contribute to the reduction of lung function. In the postoperative period, patients are predisposed to atelectasis and respiratory infections. In addition, changes in respiratory mechanics, with reduction of maximal respiratory pressures and peak expiratory flow, may occur. To compare the pre and intra-operative clinical and laboratory factors with degree of reduction of maximal respiratory pressures and peak expiratory flow in patients undergoing surgery for CABG. Sixty-one patients underwent surgery for CABG under CPB, median sternotomy, and mechanical ventilation for a period of up to 24 hours, were studied. In the day before surgery, they were interviewed and submitted to assessment of maximal respiratory pressures (maximal inspiratory and expiratory pressures, MIP and MEP) through manovacuometry and measurement of peak expiratory flow (PEF). On the fifth day after surgery, measurements of MIP, MEP, and PEF were repeated. Student's t test, Pearson's linear, and logistic regression were used to statistical analysis. Results are discussed in the significance level of 5%. General: age, 63±10 years; male, 67%; BMI, 28.0±3.8 kg/m2; hemoglobin (Hb), 12.8±1.7 g/dl; prevalence of: previous infarction 67%, systemic arterial hypertension 75%, diabetes mellitus 31%, dyslipidemia 64%, and smoking 25%. Patients with class III angina showed greater reduction of MIP compared to Abstract 60 class II (33±15% vs. 22±13%, p=0.01). COPD patients had greater reduction in maximal respiratory pressures. The higher age individuals had the lower values of MEP and PEF ...(Complete abstract click electronic access below)

Made available in DSpace on 2014-06-11T19:28:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-02-25Bitstream added on 2014-06-13T19:16:41Z : No. of bitstreams: 1 martucci_af_me_botfm.pdf: 228219 bytes, checksum: ce34b2e82a7242601a90e1e535b1b1ed (MD5) / O aumento sérico da creatinina em 0,3mg/dL define o termo lesão renal aguda (LRA) e associa-se a maior incidência de mortalidade pós-operatória em pacientes submetidos a revascularização do miocárdio. Os estudos clínicos quanto à influência da dexmedetomidina (DEX) sobre a função renal ainda são escassos. Avaliou-se a LRA no pós operatório de revascularização do miocárdio com e sem circulação extracorpórea (CEC) quando se anestesiou com DEX. Neste estudo, retrospectivo, fez-se análise seriada da creatinina sérica (CrS) até 48h de pós-operatório de 286 pacientes submetidos a revascularização do miocárdio para avaliar a incidência de LRA. Testou-se a homogeneidade entre os grupos, avaliando-se os pacientes separadamente quanto ao uso de CEC e de DEX. Cada paciente foi avaliado em relação à sua concentração sanguínea de creatinina nos períodos pré-operatório, pós-operatório imediato, de 24h e de 48h. Em cada período foi efetuada a comparação da concentração de creatinina com a concentração no pré-operatório. Se em pelo menos um dos períodos esta comparação indicou aumento de creatinina≥0,3 mg/dL, o paciente foi classificado como tendo LRA. Foi também avaliado o risco de LRA em pacientes com creatinina sanguínea pré-operatória alterada (valores entre 1,1 a 2,0mg/dL para mulheres ou 1,3 a 2,0mg/dL para homens) em comparação com os pacientes com creatinina normal.Os resultados foram homogêneos quanto a peso, idade e creatinina alterada no pré-operatório e os pacientes que fizeram uso de DEX e foram submetidos a CEC apresentaram maior incidência de LRA, com p=0,043. Dentre aqueles que não foram submetidos a CEC, houve maior incidência de LRA após DEX, porém com p=0,066.O uso da DEX no intraoperatório aumentou a incidência de LRA no pós-operatório de revascularização do miocárdio de pacientes submetidos a CEC / The increase of 0.3mg/dL in serum creatinine defines the term acute kidney injury (AKI) and is associated with higher incidence of postoperative mortality in patients undergoing coronary artery bypass grafting surgery (CABG). Clinical studies regarding the influence of dexmedetomidine (DEX) on renal function are scarce. We evaluated the LRA in postoperative of patients submitted to CABG with and without cardiopulmonary bypass (CPB) under anesthesia with DEX. In this retrospective study it was made serial analysis of serum creatinine (SCr) until 48h after the surgery of 286 patients undergoing CABG under DEX to evaluate the incidence of AKI. We tested the homogeneity among groups, evaluating patients separately for the use of CPB and DEX. Each patient was evaluated with respect to their blood concentration of creatinine in the preoperative and postoperative: early, 24h and 48h. In each period, it was compared the creatinine concentration with creatinine concentration preoperatively. If at least in one of the periods this comparison showed increased creatinine ≥ 0.3mg/dL, the patient was classified as having AKI. It has also assessed the risk of AKI in patients with preoperative blood creatinine changed: values between 1.1 to 2.0mg/dL for females or 1.3 to 2.0mg/dL for men compared with patients with normal creatinine concentration. The results were homogeneous for weight, age and creatinine concentration altered to 2.0mg/dL preoperatively. Patients who used DEX and underwent CPB had a higher incidence of AKI, with p = 0.043. Among those who were not undergoing CPB, there was a higher incidence of AKI after DEX, but with p = 0.066. Conclusion. The use of intraoperative DEX increased the incidence of AKI in the postoperative myocardial revascularization in patients undergoing CPB

Made available in DSpace on 2016-05-17T16:51:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-02-25. Added 1 bitstream(s) on 2016-05-17T16:54:37Z : No. of bitstreams: 1 000864355.pdf: 1279250 bytes, checksum: 997c584d269887d90ae842614208fa02 (MD5) / Introdução: A dor é um dos fatores que pode gerar diversas complicações ao paciente no pós-operatório (PO) principalmente devido a queda na função respiratória. A melhor analgesia no PO continua sendo um desafio. Objetivo: Verificar a ocorrência de alterações espirométricas, de força muscular respiratória e dor pós-operatória em dois grupos de pacientes submetidos à revascularização do miocárdio (RM), um com a analgesia padrão (PA) e o outro com a analgesia controlada pelo paciente (PCA) e testar se existe superioridade de um modelo analgésico sobre o outro. Casuística e métodos: o estudo foi realizado em pacientes submetidos à RM com circulação extracorpórea, no Hospital das Clínicas da Faculdade de Medicina de Botucatu. Eles foram divididos em grupos de acordo com a forma de analgesia pós-operatória: PA ou PCA. A determinação da alocação dos pacientes nos grupos foi aleatória. Os voluntários foram avaliados por meio de ficha com dados e antecedentes pessoais, hábitos de vida, informações sobre as características do procedimento cirúrgico; além de testes específicos como: espirometria (CVF, VEF1 e VVM), manovacuometria (pressão inspiratória máxima (PImáx) e pressão expiratória máxima (PEmáx)), e escala da dor. A avaliação dos pacientes foi realizada nos momentos: pré-operatório, do primeiro ao terceiro e sétimo PO (1PO, 2PO, 3PO e 7PO), com exceção da espirometria que foi realizada no pré-operatório e no 7PO. Resultados: Foram avaliados 60 pacientes (30 no grupo PA e 30 no grupo PCA). O perfil demográfico dos pacientes foi semelhante nos dois grupos, com exceção da hipertensão arterial sistêmica que esteve presente em 100% dos pacientes de PA e em 86,7% de PCA. Em relação às variáveis espirométricas analisadas em porcentagem do predito, o grupo PCA apresentou valores significativamente maiores de CVF (76,73% X 67,17%), de VEF1 (76,3% X 64,9%) e da VVM (89,17% X 72,23%) no... / Introduction: Pain in the postoperative days (POD) can lead to several complications to the patient, mainly due to decrease in respiratory function. The best analgesia in POD remains a challenge. Objective: To investigate the occurrence of spirometric changes, respiratory muscles' strength changes and post-operative pain in patients undergoing coronary artery bypass grafting (CABG) receiving different POD analgesia. Also, to determine whether there is a superiority of one analgesic model over the other. Patients and methods: Patients undergoing CABG with extra-corporeal circulation at University Hospital of the Botucatu Medical College were included in the study. They were randomly divided into 2 different groups according to the type of postoperative analgesia: one with the Standard Analgesia (SA) and the other with Patient-Controlled Analgesia (PCA). Volunteers were evaluated through a questionnaire with personal data, past medical history, lifestyle, characteristics of the surgical procedure; as well as specific tests such as spirometry (FVC, FEV1 and MVV), vaccum-manometry (maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP)), and pain scale. The questionnaire was applied: pre-operatively and in post-operative days 1,2,3 and 7 (POD 1, POD 2, POD 3, POD 7). The spirometry was performed only preoperatively and in the POD 7. Results: 60 patients were evaluated (30 in the SA group and 30 in the PCA group). Both groups were demographically similar, except for hypertension that was present in 100% of SA patients and in 86.7% of PCA. Regarding the spirometric variables in percentage of predicted, the PCA group had significantly higher FVC (76.73% vs. 67.17%), FEV1 (76.3% vs. 64.9%) and MVV (89.17% vs. 72.23%) compared to POD 7 in SA group. MIP did not differ between the 2 groups and MEP was significantly higher in the PCA group only in POD 3 (61.17 ± 15.57 cmH2O X 46.83 ± 12.28 cm H2O). Pain when assessed at rest ...

Made available in DSpace on 2015-04-09T12:28:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-02-18Bitstream added on 2015-04-09T12:48:22Z : No. of bitstreams: 1 000814364.pdf: 804394 bytes, checksum: 8d0c71790257ab625debb675d6d674cf (MD5) / A cardiotoxicidade induzida pela doxorrubicina gera remodelamento miocárdico e disfunção sistólica. O presente estudo avaliou a participação da apoptose e componentes da matriz extracelular (miofibroblastos e fibronectina) na cardiomiopatia dilatada induzida com doxorrubicina em coelhos. Foram utilizados 25 coelhos da raça Nova Zelândia, alocados em dois grupos (controle e tratados). O fármaco foi administrado por seis semanas e a ecodopplercardiografia foi realizada no momento zero e após a última administração. O remodelamento do miocárdio foi avaliado por microscopia eletrônica (varredura e transmissão) e por imunodetecção de fibras apoptóticas, miofibroblastos e fibronectina. Nos animais tratados houve redução significativa da função sistólica observada na ecodopplercardiografia e aumento das fibras apoptóticas e miofibroblastos, no ventrículo esquerdo, septo interventricular e ventrículo direito. Houve correlação negativa significativa entre o número de mitocôndrias lesadas e das células apoptóticas no septo interventricular e no ventrículo esquerdo com os índices de função sistólica. Os dados obtidos permitem inferir que a apoptose por via mitocondrial participa da disfunção sistólica observada no tratamento com doxorrubicina e que o aumento da matriz extracelular não é o principal causador de disfunção sistólica na cardiomiopatia dilatada induzida com doxorrubicina / The cardiotoxicity induced by doxorubicin generates myocardial remodeling and systolic dysfunction. The present study evaluated the role of apoptosis and extracellular matrix components (fibronectin and myofibroblasts) in doxorubicin-induced dilated cardiomyopathy in rabbits. Twenty five New Zealand rabbits were used, allocated into two groups (control and treated). The drug was administered for six weeks and Doppler echocardiography was performed before the first and after the last administration. Myocardial remodeling was evaluated by electron microscopy (scanning and transmission) and immunodetection of apoptotic cells, myofibroblasts and fibronectin. Significant reduction in systolic function, increased apoptotic fibers and myofibroblasts were noticed in treated animals, on the left ventricle, interventricular septum and right ventricle. There was a significant negative correlation between the number of damaged mitochondria and apoptotic cells at the left ventricle and interventricular septum with systolic function, showing that the apoptosis by mitochondrial pathway plays a role on the systolic dysfunction during treatment with doxorubicin and the increase in extracellular matrix is not the primary cause of systolic dysfunction induced by doxorubicin

Dissertação (Mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências da Saúde. / Made available in DSpace on 2012-10-17T04:28:30Z (GMT). No. of bitstreams: 0Bitstream added on 2016-01-08T22:57:35Z : No. of bitstreams: 1 151072.pdf: 10665695 bytes, checksum: 052608cfba69ddf4c6c947b2dc10a3b3 (MD5)