Introdução: Diversas condições clínicas podem modificar a resposta ao tratamento trombolítico no acidente vascular isquêmico agudo. O grau de comorbidade dos pacientes medido pelo Índice de Charlson, um índice que mede o grau de comorbidades clínicas em AVC, tem valor prognóstico na incapacidade pós-AVC tanto em populações com acidente vascular do tipo hemorrágico como isquêmico. Objetivo: Avaliar o efeito do grau de comorbidade aferido pelo índice de Charlson na resposta ao tratamento trombolítico no acidente vascular isquêmico e a incapacidade na alta hospitalar. Métodos: Estudo de coorte prospectivo de 96 pacientes tratados com trombólise para o acidente vascular isquêmico, avaliando o impacto das comorbidades clínicas na resposta ao tratamento trombolítico no AVC isquêmico. Os pacientes foram divididos em dois grupos, aqueles com alto ou baixo grau de comorbidades clínicas, conforme o índice de Charlson. A evolução após o tratamento foi aferida pelo escore de gravidade dos sintomas de acordo com a escala do NIHSS medido antes da infusão, imediatamente após o tratamento, 24horas e 7 dias após a trombólise. A incapacidade na alta foi avaliada pela escala modificada de Rankin sendo, considerada boa resposta a pontuação 0-1 e sua frequência comparada entre os dois grupos de pacientes. Resultados: A comparação dos escores médios do NIHSS mostraram diferenças significativas nos diferentes momentos entre os grupos de alta e baixa comorbidade (Wilk's Lambda test F (1,92) = 24.293; p< 0.001). Pacientes com índice de comorbidade baixo apresentaram redução do escore do NIHSS de 10.13 para 2.9, enquanto que no grupo com alta comorbidade, o tratamento trombolítico demostrou pouco efeito. Uma boa evolução, definida como incapacidade 0 e 1 na escala modificada de Rankin, foi observada em (73%) dos pacientes com baixo índice de comorbidade, enquanto somente (15%) dos pacientes com alto índice de comorbidade apresentaram essa evolução favorável, uma diferença clinicamente muito significativa (RR 5.62; 95% CI = 2.97 a 10.65; p< 0.001). Conclusão: A presença de comorbidades clínicas medida peloíndice de Charlson foi associada a uma menor resposta neurológica no tratamento trombolítico do AVC isquêmico e a um maior grau de incapacidade funcional na alta. / Background and purpose: Clinical comorbidities modify prognosis in haemorrhagic and ischaemic stroke. Charlson Comorbidity index is a validated and useful tool for evaluating comorbidity in stroke. In this study we evaluated the effect of clinical comorbidities as measured by Charlson Comorbidity Index in the in ischaemic stroke thrombolysis. Methods: Prospective cohort study of 96 thrombolysis treated ischaemic stroke patients. The cohort population was divided in two groups according with severity of Charlson Comorbidity Index. During study, NIHSS score was evaluated four times (pre, post, 24 hours and 7 days after thrombolysis) and lower or higher comorbidities groups were compared using repeated measures ANOVA. Response to thrombolysis in both groups was also analysed with disability modified Rankin scale. Results: We observed differences in evolution of mean NIHSS scores between higher and lower clinical comorbidity groups. Patients with low clinical comorbidities experiencing a significant reduction of NIHSS score that ranged from 10.13 to 2.9 points, while patients in the HIC group had initial NIHSS score of 14.75 and final NIHSS score of 13.78 (Wilk's Lambda test F (1,92) = 24.293; p< 0.001). Lack of response to thrombolysis had direct relation with disability at hospital discharge. Better clinical outcome, as evaluated by modified Rankin scale of 0 and 1, was markedly different between groups, with 23 (73%) versus 9 (15%) in low and high clinical comorbidities patients respectively (RR=5.62; 95%CI=2.97 to 10.65; p< 0.001). Conclusion: High level of clinical comorbidities negatively influences response to thrombolysis, attenuating treatment related reduction of stroke symptoms severity and increasing the frequency of disabled patients at discharge.

O presente trabalho objetivou explorar a eventual variação da expressão do mRNA e da proteína S100b no hipocampo, cerebelo e córtex cerebral de ratos neonatos em condições de anóxia, comparativamente à condições controle. Este estudo foi desenvolvido em ratos albinos, divididos em dois grupos: o grupo Experimental Anóxia (EA) e o grupo Experimental Controle (EC), que por sua vez foram subdivididos em tempos de 2, 4, 6, 12 e 24 horas no que se refere à coleta de amostras após a aplicação dos estímulos pré-estabelecidos para cada grupo. Dos períodos avaliados, nossos resultados indicaram que a anóxia proporcionou um pico na expressão gênica de S100b após duas horas e proteica após 4 horas nas áreas do hipocampo e cerebelo. O córtex cerebral do grupo EA quando comparado ao grupo EC, não apresentou nenhum aumento significante de S100b nos períodos avaliados. Os resultados obtidos contribuem de forma crucial para elucidação do papel da proteína S100b como biomarcadora na EHI, bem como no esclarecimento parcial da função deste gene com relação à fisiopatologia da doença. / The aim of the present study was to investigate the temporal variation in the expression of S100b mRNA and protein in the hippocampus, cerebellum, and cerebral cortex of newborn rats under conditions of anoxia compared with control rats. The study was performed using two groups albino rats: Experimental Anoxia (EA) and Experimental Control (EC). The animals in both EA and EC were distributed in the following subgroups relative to the time elapsed since the application of the stimuli predefined for each group: two, four, six, 12, and 24 hours. Anoxia induced a peak in the S100b gene expression after two hours and protein expression after 4 hours in the hippocampus and cerebellum. With respect to the cerebral cortex, S100b never exhibited a significant increase in the EA group compared with the EC group. The results of the present study represent a crucial contribution to the elucidation of the role protein S100b plays as a biomarker in HIE, as well as a contribution to the elucidation of the role the corresponding gene plays in the physiopathology of the disease.

Introdução: O aumento da tolerância do miocárdio isquêmico observado durante o segundo de dois testes de esforços seqüenciais, o fenômeno do pré-aquecimento, foi proposto como um modelo clínico do pré-condicionamento isquêmico. Bloqueadores dos canais de K-ATP dependentes, tais como as sulfoniluréias, podem induzir a perda do pré-condicionamento isquêmico, o qual poderia estar envolvido no aumento dos eventos cardiovasculares. A repaglinida é um agente hipoglicemiante oral, pertencente à família da meglitinida e supostamente dotada de menor efeito no pré-condicionamento isquêmico, ainda que o fármaco tenha seu principal mecanismo de ação nos canais de K-ATP dependentes. Objetivos e Métodos: O objetivo foi investigar os efeitos da repaglinida no fenômeno do pré-condicionamento isquêmico em pacientes diabéticos com doença coronariana estável. Foram estudados 42 pacientes diabéticos tipo 2, com angina estável e doença arterial documentada. Todos os pacientes tinham testes ergométricos positivos para isquemia. Na primeira fase do teste, a sulfoniluréia e os betabloqueadores foram suspensos por trinta dias e sete dias, respectivamente. Os pacientes foram submetidos a dois testes ergométricos seqüenciais, com intervalo de trinta minutos (testes 1 e 2). Na segunda fase, os pacientes receberam repaglinida por sete dias e mais dois testes ergométricos foram repetidos (testes 3 e 4). Resultados: Todos os pacientes alcançaram ST >1 mm na primeira fase (Teste 1 e 2). O tempo alcançado no teste 2 foi maior que aquele alcançado no teste 1 (4:44s. x 5:37s. p=0,001), como também foi maior a duração do exercício (6:15s x 6:29s. p=0,008), denotando pré-condicionamento isquêmico. Após o uso da repaglinida, nos testes 3 e 4, observou-se menor tempo alcançado para atingir isquemia no teste 4 (5:37s. x 4:58s. p=0,001). Observou-se, ainda, menor tempo de tolerância ao exercício na fase 2 (6:57s x 6:34s. p=0,007). Em relação ao surgimento de angina, não se constataram diferenças estatísticas entre as duas fases. Conclusão: Nos pacientes diabéticos com doença coronariana estável, a repaglinida bloqueou o pré-condicionamento isquêmico. / Background: The increase of tolerance to myocardial ischemia observed during the second of two sequential exercise tests, the warm-up phenomenon, has been proposed as a clinical model of ischemic preconditioning. Blockers of K-ATP channels, such as the Sulfonylurea drugs, can induce loss of ischemic preconditioning, what could be involved in an increase of cardiac events. Repaglinide is a hypoglycemic agent with supposedly lower influence on ischemic preconditioning, despite acting in K-ATP channels. Objectives and Methods: This study investigated the effects of repaglinide on the ischemic preconditioning in diabetic patients with CAD. There were 42 patients and inclusion criteria were positive treadmill test for myocardial ischemia. Sulphonylureas and beta-blocking agents were withdrawn 30 and 7 days respectively before phase 1 of the study. In this phase, the patients underwent two consecutive treadmill exercise tests at 30 minute intervals (test 1 and test 2). In phase 2 of the study, all patients received repaglinide 2 mg three times daily during 7 days before treadmill exercise test (test 3 and test 4). Results: All patients achieved 1.0 mm ST-segment depression during phase 1. The time achieved to ST depression during test 2 was greater than that during test 1 (4:44s vs. 5:37s. p=0.001) as well as the duration of the exercise (6:15s vs.6: 29s. p=0.008), suggesting a higher ischemic threshold. In phase 2 after repaglinide, all patients achieved 1 mm ST-segment depression. However, the time achieved to ST depression, as well as the duration of the exercise, was lower in test 4 comparing with test 3. There were no statistical differences regarding angina episodes in phase 1 or phase 2. Conclusions: In diabetic patients with stable coronary disease, the oral hypoglycemic agent repaglinide abolished the myocardial ischemic preconditioning.

Made available in DSpace on 2015-04-20T12:31:47Z (GMT). No. of bitstreams: 1 Jaime Arnez.pdf: 2202191 bytes, checksum: 2925f1eec50bb2ccb5e644dc0dad1780 (MD5) Previous issue date: 2013-03-30 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / Heart failure (HF) affects approximately 2% of the world population. Ischemic cardiomyopathy accounts for two-thirds of cases of HF, which, when established, leads to physical limitations, multiple hospital admissions, declining quality of life, and increasing morbidity and mortality. Therapeutic alternatives range from pharmacological treatment to heart transplantation. Modern reperfusion strategies and advanced pharmacotherapeutic management have contributed to increase the survival of patients with ischemic cardiomyopathy, but none of these treatment strategies can reverse damage to cardiomyocytes or recover lost vasculature. Within this context, the concept of regenerative medicine, using stem cells (SC) for tissue repair, may become a reality. Mobilization and implantation of autologous, CD34+ hematopoietic SCs may improve myocardial function and perfusion. A total of 15 patients with severe ischemic cardiomyopathy, not eligible for other therapeutic alternatives, received autologous CD34+ cells collected from peripheral blood (PB) after G-CSF mobilization. SCs collected from PB were implanted in the myocardium using two routes (intracoronary and via the coronary sinus). All patients underwent clinical, laboratory, and imaging-based assessment to evaluate left ventricular function, perfusion and voltage. All patients were reevaluated after 4 months of post-implantation follow-up. Of the 15 initial patients, two died during follow-up (late post-implantation mortality). The different variables analyzed at 4-month follow-up showed improvement in functional classification (p=0.014), angina score (CCS) (p=0.006), the six-minute walk test (p=0.005), and quality of life (p=0.003). There was minor improvement in ejection fraction, as analyzed by echocardiography and magnetic resonance imaging, without reaching statistical significance (p=0.062 and p=0.0397 respectively); myocardial perfusion scintigraphy showed a non-significant improvement in viability (20.79% to 27.14%, p=0.390). Electroanatomic mapping of the left ventricle did not show any significant changes in electrical activity (p=0.767). CD34+ SC implantation into the myocardium using two routes simultaneously is a safe procedure. At 4-month follow-up, patients experienced improvement in symptoms and quality of life, but without significant improvement in left ventricular function, perfusion and voltage. Key words: Cell therapy, G-CSF, CD34+, ischemic cardiomyopathy / A insuficiência cardíaca (IC) acomete aproximadamente 2% da população mundial. A cardiopatia isquêmica é responsável por 2/3 da IC, a qual, quando estabelecida, implica limitações físicas, repetidas internações hospitalares, piora da qualidade de vida e aumento da morbimortalidade. As alternativas terapêuticas variam desde o tratamento farmacológico até o transplante cardíaco. Modernas estratégias de reperfusão e avançadas condutas farmacológicas têm propiciado um aumento na sobrevida dos pacientes com cardiopatia isquêmica, porém nenhuma estratégia de tratamento recupera o dano aos cardiomiócitos e à vasculatura perdida; é nesse sentido que o conceito de medicina regenerativa utilizando células-tronco (CT) para o reparo de tecidos pode tornar-se realidade. A mobilização e implante autólogo de CT hematopoéticas CD34+ podem melhorar a função e perfusão. Um total de 15 pacientes com cardiopatia isquêmica grave, inelegíveis para outra alternativa terapêutica, receberam células autólogas CD34+ coletadas de sangue periférico (SP), previamente mobilizadas com fator de estimulação de colônias de granulócitos (G-CSF). As CT coletadas de SP foram implantadas no miocárdio utilizando duas vias (intracoronariana e seio coronariano). Realizou-se em todos os pacientes uma avaliação clínica, laboratorial e exames complementares de imagem para avaliar função, perfusão e voltagem do ventrículo esquerdo. Após 4 meses de seguimento pós-implante, todos os pacientes foram reavaliados. Dos 15 pacientes incluídos, dois foram a óbito durante o seguimento (pós-implante tardio). As diferentes variáveis analisadas no seguimento de 4 meses mostraram uma melhora na classe funcional (p = 0,014), escore de angina (Canadian Cardiovascular Society) (p = 0,006), teste da caminhada de 6 minutos (p = 0,005) e qualidade de vida (p = 0,003). A fração de ejeção analisada por ecocardiograma e ressonância magnética mostrou uma discreta melhora, porém sem significância estatística (p = 0,062 e p = 0,0397); a cintilografia do miocárdio mostrou uma melhora da viabilidade, porém sem significância (20,79 para 27,14%; p = 0,390); a atividade elétrica do ventrículo esquerdo realizada através do mapeamento eletroanatômico não mostrou alterações significativas (p = 0,767). O implante de CT CD34+ no miocárdio utilizando duas vias simultâneas é seguro. No seguimento de 4 meses os pacientes apresentaram uma melhora em relação à sintomatologia e qualidade de vida, porém sem melhora significativa na função, perfusão e voltagem do ventrículo esquerdo

No presente trabalho, estudaram-se os efeitos da l-alanil glutamina (Ala-Gln), do precondicionamento isquÃmico (PCI) e das duas tÃcnicas concomitantemente sobre a lesÃo pulmonar provocada por isquemia e reperfusÃo (I/R) causada por pinÃamento da aorta infra-renal em ratos. Foram utilizados 60 ratos machos Wistar, randomizados em cinco grupos (n = 12) divididos em dois tempos (n = 6): Grupo Simulado, Grupo I/R, Grupo PCI + I/R, Grupo Ala-Gln + I/R, Grupo Ala-Gln + PCI + I/R. Tempos: T1 (4h de isquemia) e T2 (4 horas de isquemia e 1h de reperfusÃo). Todos os grupos receberam soluÃÃo salina previamente, menos os grupos prÃ-tratados com Ala-Gln que receberam o dipeptÃdeo e soluÃÃo salina em igual volume. Foi utilizado o modelo de pinÃamento da aorta infra-renal com 4 horas de isquemia e 1 hora de reperfusÃo. Determinaram-se as concentraÃÃes de mieloperoxidase (MPO) pulmonar, substÃncias reativas ao Ãcido tiobarbitÃrico (TBARS) e glutationa reduzida (GSH) no sangue e pulmÃo para avaliar os grupos em estudo. O teste de Kolmogorov-Smirnoff mostrou distribuiÃÃo normal dos dados. Dados expressos como mÃdia acompanhada pelo seu desvio padrÃo (MÃdia  DPM) sendo realizado teste t de Student. Para anÃlise comparativa simultÃnea de trÃs grupos utilizou-se o teste Anova com pÃs-teste de Tukey. Em todos os casos foi adotado o nÃvel de significÃncia de p<0,05. Houve elevaÃÃo das concentraÃÃes de MPO pulmonar tanto no grupo submetido à isquemia quanto no grupo que realizou a I/R. Ocorreu reduÃÃo significante das concentraÃÃes de MPO pulmonar nos grupos submetidos à isquemia prÃ-tratados com Ala-Gln e com PCI. Na avaliaÃÃo dos grupos que sofreram I/R nÃo foi observada alteraÃÃo nas concentraÃÃes de MPO nos grupos prÃ-tratados Ala-Gln ou PCI. O grupo prÃ-tratado com as duas tÃcnicas apresentou aumento significante da MPO nos tempos estudados. A Ala-Gln como prÃ-tratamento isolado reduziu TBARS plasmÃtico na isquemia e o aumentou no pulmÃo na I/R. Jà no pulmÃo durante isquemia e no plasma na I/R houve reduÃÃo da GSH. O PCI como prÃ-tratamento isolado elevou o TBARS pulmonar na I/R e reduziu a GSH pulmonar na I/R. A associaÃÃo da Ala-Gln e PCI acresceu o TBARS plasmÃtico na isquemia, tambÃm o elevando no pulmÃo e mÃsculo na I/R. Jà a GSH, com os dois prÃ-tratamentos, sofre reduÃÃo plasmÃtica na isquemia e pulmonar na I/R, com elevaÃÃo plasmÃtica na I/R. O presente estudo demonstra que tanto o prÃ-tratamento com Ala-Gln como o PCI protegem contra a lesÃo isquÃmica à distÃncia, em modelo murino de pinÃamento da aorta infra-renal quando avaliado MPO pulmonar. O mesmo nÃo ocorre na lesÃo por I/R. NÃo hà benefÃcio, e sim agravamento de lesÃo à distÃncia pulmonar, na associaÃÃo dos dois prÃ-tratamentos ao mensurar a MPO pulmonar. / The present work determined the effects of pre-treatment with L-alanyl glutamine (Ala-Gln) and ischemic preconditioning (IPC), alone and in combination, against lesions caused by I/R by clamping the infrarenal aorta in rats. Sixty Wistar rats were distributed into five groups (n = 12) divided into two times (n = 6): Control, Group I/R, Group IPC + I/R, Group Ala-Gln + I/R, Group Ala-Gln + IPC + I/R. Times: T1 (infrarenal-aorta clamping ischemia-4h); T2 (ischemia-4h plus reperfusion-1h). Pulmonary myeloperoxidase (MPO) and plasma TBARS concentrations were measured. Data expressed as mean  standard-deviation, analyzed by Studentâs t-test and ANOVA/Tukeyâs post-test. P-values < 0,05 were considered significant. Increased MPO concentrations in ischemic group and in I/R group occurred as compared to control. Reduction in MPO concentrations happened in ischemic groups pre-treated with either Ala-Gln or IPC. I/R induced no change in MPO concentrations in groups pre-treated with either Ala-Gln or IPC. Pre-treating with the two procedures showed increased MPO at both times studied. Reduction in TBARS concentrations occurred in Ala-Gln pre-treated group, whereas significant elevation was observed when Ala-Gln and IPC were associated in ischemic animals. Ischemia/reperfusion induced elevation of plasma TBARS. Pre-treatment with either Ala-Gln or IPC protects against distant pulmonary lesion due to ischemia. The same did not occur in I/R lesion. Combining the two procedures aggravated inflammation indicated by increased MPO concentrations. Elevated TBARS concentrations in ischemic animals pre-treated with the two procedures indicate increased lipid peroxidation, whereas pre-treatment with Ala-Gln induced decreased TBARS concentrations.

Introdução: O Acidente Vascular Cerebral (AVC) é a maior causa de morte no Brasil e um dos maiores responsáveis por incapacitação e invalidez. Existem informações insuficientes quanto aos principais fatores associados à ocorrência de óbito nos pacientes vítimas desta enfermidade. Alguns escores preditores foram desenvolvidos porém não foram validados em população brasileira até o momento. Uma das ações mais importantes na redução do ônus do AVC é o atendimento sistematizado destes pacientes de forma mulltidisciplinar em Unidades de AVC (UAVC) com potencial aumento do uso da terapia trombolítica, além da estratificação dos pacientes, possibilitando decisões terapêuticas mais precoces. Este estudo traz informações sobre o perfil epidemiológico dos pacientes admitidos na UAVC do Hospital Geral de Fortaleza (HGF), bem como identifica fatores preditores de mortalidade e incapacidade até a alta hospitalar e busca validar o Escore de Risco do Registro da Rede Canadense de AVC (IScore), possibilitando a utilização desta ferramenta na estratificação de risco de morte e incapacidade em uma população distinta daquela originalmente realizada. Objetivos: avaliar perfil clínico-epidemiológico dos pacientes e identificar fatores preditores independentes de mortalidade e incapacidade (primários); validar o iScore para morte ou incapacidade e desenvolver um escore na amostra para morte e incapacidade (secundários). Métodos: Foram selecionados pacientes consecutivos admitidos na Unidade de AVC do HGF entre novembro de 2009 até maio de 2012 com diagnóstico clínico de AVC isquêmico. Os dados foram coletados por equipe treinada e através de um formulário específico. Foi realizada análise univariada (método do quiquadrado) e análise multivariada (com regressão logística, stepwise forwardbackward) para descrição das características e identificação dos fatores associados ao desfecho. Teste de correlação de Pearson e curva ROC foram utilizados para medidas de correlação e desempenho dos escores prognósticos. Resultados: no período entre novembro de 2009 e maio de 2012 foram elegíveis 1433 pacientes, sendo 780 analisados. Houve predomíno do sexo masculino e a média de idade (± desvio padrão) foi de 66,1 anos (± 15,44). A forma de apresentação mais comum foi a fraqueza muscular (653 pacientes, 83,6%). O desfecho combinado ocorreu em 423 pacientes (45,8%) e 40 pacientes (5,1%) morreram. Foram identificados 8 fatores preditores independentes para o desfecho. O iScore apresentou bom desempenho, com AUC de 0,797 e Correlação de Pearson de 0,989. Conclusão: Pacientes com AVCi tem altas taxas de incapacidade ou morte até a alta de uma unidade de AVC. Medidas populacionais de informação tem potencial para reduzir a ocorrência dos desfechos. Foram identificados oito fatores preditores de mortalidade ou incapacidade. O iScore apresentou bom desempenho na amostra e pode ser utilizado com acurácia na população brasileira como ferramenta prognóstica. / Intoduction: Stroke is the leading cause of death and one of the most important disease associated with disability in Brazil. There is insufficient information about factors associated with death in stroke patients. Some death risk score has been developed, but none of them were applied in the Brazilian population yet. One of the most important actions to be done to reduce the burden of the stroke is the multidisciplinary assessment of the patients in stroke units (UAVC), with the potential to improve the thrombolytic therapy utilization and the early stratification of patients, allowing earlier treatment decisions. The present study, provides information on the epidemiological profile of patients admitted to the stroke unit in the Hospital Geral de Fortaleza (HGF), identifies predictors of in-hospital mortality and disability and seeks to validate the IScore, allowing the use of this tool to stratify the risk of death and disability in a population different from that which was originally derived. Objectives: to evaluate patient epidemiologic and clinical patterns and factors independently associated with death and disability at hospital discharge (primary objectives); to validate the iScore fitness to predict mortality and/or disability and to develop a new risk score to predict mortality and disability at discharge (secondary objectives). Methods: all consecutive patients admitted to the Hospital Geral de Fortaleza Stroke Unit since November 2009 until May 2012 were elegible. Data were collected by a trained team and by using a specific clinical research form. Univariable analysis (by chi-square test) followed by multivariable analysis (with logistic regression) were performed to identify and establish the variables associated with the outcome (death or disability at hospital discharge). Additionally, Pearson correlation test and ROC curve to measure the iScore correlation and discrimination ability were conducted. Results: a total of 1433 patients were selected and 781 considered eligible were included for the analysis. Male gender were more frequent; mean age was 66,1 (± 15,44). The most common clinical pattern at hospital arrival was \"weakness\" (653 pacientes, 83,6%). Outcome occurred in 423 patients (58,6%) and 40 patients (5,1%) had died. Eight factors were independently associated with outcome. The iScore had good performance, with AUC of 0,797 and Pearson Correlation Test of 0,985. Conclusion: Stroke patients have substantial rate of death or disability at hospital discharge. Populationbased strategies to inform about the signs and symptoms of stroke have potential to decrease this rate. Eight factors were identified as predictors of death or disability and might be used to support patient risk stratification. The iScore had a good performance in the sample and can be used with accuracy as a prognostic tool in Brazil.

Orientador: Fernando Cendes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-19T20:24:08Z (GMT). No. of bitstreams: 1 Tedeschi_GuilhermeGarlipp_M.pdf: 7486635 bytes, checksum: b738f054440da6d0b0f0d6b7055bde2b (MD5) Previous issue date: 2012 / Resumo: Introdução: O Acidente Vascular Encefálico (AVE) é uma importante doença, com enorme implicação em fatores sociais e econômicos em todo o mundo, sobretudo no Brasil, onde é classificado como a maior causa de morte de origem cardiovascular, além de ser a principal responsável por grave morbidade, que traz incapacidade funcional e dependência ao paciente. A terapia com o Fator Ativador do Plasminogênio Tecidual (rt-PA), na fase aguda, imediatamente pós ictus do AVE, vem sendo muito utilizada mundialmente para o restabelecimento da circulação cerebral no AVE isquêmico, com grande influência na recuperação das habilidades motoras. Diversas são as formas de quantificar os danos ocorridos pelo AVE, entre eles o exame de Ressonância Magnética (RM), que é capaz de apresentar resultados precisos para diagnóstico clínicos e outros tipos de investigação menos explícitos, que contribuem para a mensuração da lesão celular e sua consequente recuperação. Objetivo: O presente estudo tem como objetivo principal, avaliar a espessura cortical dos pacientes, em dois diferentes períodos do AVE (Agudo e Crônico) e estabelecer associações em relação à função motora e o tempo de início da trombólise. Metodologia: Pacientes (33) com AVE isquêmico, trombolizados (T) e não trombolizados (NT), foram avaliados com RM e escalas funcionais (Fugl Meyer, MIF e FAC) em dois momentos da evolução da doença, sendo o agudo com 62,67 dias após o AVE e o crônico (follow up) com 419,22 dias após AVE. O tempo de início de tratamento com o trombolítico foi dividido em mais de 150 minutos (Grupo D) e Menos de 150 minutos (Grupo A). A análise estatística foi realizada pelo programa Freesurfer, ferramenta Qdec, que analisou as imagens (p<0,05) e pelo programa Systat 9. Resultados: A análise de todas as imagens (agudo e crônico) mostrou maior espessura cortical no grupo crônico, sendo que o mesmo acorre para o grupo T na fase crônica, para o grupo A na fase aguda e para o grupo D na fase crônica. Observou-se aumento na espessura cortical de áreas cerebrais específicas (Wernicke e giro pré central) entre as fases aguda e crônica. Observou-se também ganho funcional significativo (p < 0,05) em relação às escalas Fugl Meyer e MIF entre os períodos agudo e crônico / Abstract: Introduction: Stroke is an important disease with great implications in social and economic factors around the world, especially in Brazil, where is ranked as the first cardiovascular cause of death and the main cause of morbidity, which generates functional disability and some level of dependence on the patient. Thrombolysis with tissue plasminogen activator factor (rt-PA) on acute phase of stroke, immediately after ictus, has been widely used worldwide for the restoration of cerebral circulation in ischemic stroke, with great influence on the recovery of motor skills. There are several ways to quantify the damage incurred by stroke, including magnetic resonance imaging (MRI), which is able to provide accurate results for diagnostic and other not too explicit research results that contribute to the measurement of cell damage and its subsequent recovery. Objective: The main objective of the present study is to evaluate cortical thickness in two different periods of the stroke (Acute and Chronic) and establish associations in relation to motor function and the time of thrombolysis. Methodology: Patients (33) with ischemic stroke were evaluated with MRI and functional scales (Fugl Meyer, FIM and FAC) in two stroke stages, the acute phase with 62.67 days post-stroke and chronic phase (follow up), with 419.22 days after stroke. The time of thrombolytic treatment was divided into more than 150 minutes (Group D) and less than 150 minutes (Group A). MRI images statistical analysis were performed by the software Freesurf, Qdec tool (p < 0.05) and other analysis were performed by Systat 9. Results: The analysis of all images showed increased cortical thickness in chronic group. Same results were found at T group in the chronic phase, at A group in acute phase and at D group in the chronic phase. Increased cortical thickness was observed in specific areas (Wernicke and precentral gyrus) between acute and chronic phases. Functional gain was significant (p < 0.05) compared to the scales Fugl Meyer and FIM periods between acute and chronic / Mestrado / Neurociencias / Mestre em Fisiopatologia Médica

Abstract During cardiac and aortic surgery, disturbance of the blood supply in the central nervous system occurs when the repair of aortic pathologies is performed or a bloodless operation field is needed in complex cardiac surgery. To enable the suitable operation environment, the technique named hypothermic circulatory arrest (HCA) has been utilized via heart-lung machine. In this method, the core temperature is lowered to the target temperature, after which blood circulation is halted for a certain period of time. A challenge is that the successful usage of HCA, however still involves the risks of postoperative neurological complications and mortality. In cardiac and aortic arch surgery, the brain is at the highest risk for deficits, whereas in the repair of thoracoabdominal aortic aneurysms (TAAAs), spinal cord injury remains the most severe adverse outcome. Adjunctive protective strategies are required to reduce ischemic injury in these settings. In this thesis, Studies I and II focused on the spinal cord and the Study III on the brain. The studies were performed using acute (II, III) or subacute (I) experimental porcine models, primarily aiming to assess the effectiveness of remote ischemic preconditioning (RIPC) in spinal cord protection along with the aim of studying the underlying mechanisms of RIPC in neuroprotection. Studies I and II demonstrated enhanced motor evoked potential (MEP) responses in both hind limbs, indicating spinal cord protection by RIPC. The faster recovery of brain damage marker S100B along with higher cardiac index and lower systemic lactate levels confirmed the cardio- and neuroprotective properties of RIPC in Study III. The protective mechanism of RIPC was associated with increased antioxidant response (II, III). / Tiivistelmä Sydän- ja aorttakirurgiassa, keskushermoston verenkiertoa joudutaan häiritsemään toteutettaessa aortan korjausleikkauksia tai vaikeissa sydänkirurgisissa toimenpiteissä verettömän leikkausalueen saavuttamiseksi. Sydän-keuhkokoneen avulla toteutettava täydellinen verenkierron pysäytys mahdollistaa vaaditut olosuhteet. Tässä menetelmässä ydinlämpötilaa lasketaan ja verenkierron pysäytys toteutaan tavoitellussa kohdelämpötilassa tietyssä aikaikkunassa. Kyseisen menetelmän onnistunut käyttö sisältää kuitenkin riskejä operaatioiden jälkeisiin neurologisiin komplikaatioihin ja kuolleisuuteen. Sydämen ja aortankaaren kirurgiassa aivot ovat suurimmassa vaarassa vaurioille. Rinta- ja vatsa-aortan aneurysmien eli pullistumien korjausleikkauksiin liittyvä selkäydinvaurio on puolestaan yksi vakavimmista ja vaikeimmista seurauksista. Lisäsuojausmenetelmiä tarvitaan vähentämään iskeemistä vauriota näissä asetelmissa. Väitöskirjan osatyöt I ja II keskittyivät selkäytimeen. Osatyö III käsitteli puolestaan aivojen suojausta. Osatyöt toteutettiin akuutteina (II, III) ja subakuutteina (I) kokeellisina porsasmalleina. Tutkimusten tavoitteina oli arvioida esialtistavan perifeerisen raajaiskemian vaikuttavuutta selkäytimen suojauksessa sekä tutkia raajaiskemian taustalla olevia mekanismeja hermokudoksen suojauksessa. Osatöissä I, II havaittiin motoristen herätepotentiaalien parantuneita vasteita molemmissa takajaloissa osoittaen esialtistavan raajaiskemian suojaavan selkäydintä simuloidussa rinta-aortan korjaustoimenpiteessä. Osatyö III keskittyi alhaisessa lämpötilassa toteutettavaan täydelliseen verenkierron pysäytykseen. Tässä tutkimuksessa todetut aivovauriomarkkeri S100B tason nopeampi lasku, korkeampi sydänindeksi ja alhaisemmat laktaattitasot varmistivat raajaiskemian sydän- ja hermokudossuojausvaikutusta. Esialtistavan perifeerisen raajaiskemian suojaava mekanismi voidaan liittää parantuneeseen solujen antioksidanttivasteeseen (II, III).

Abstract Interest in off-pump coronary surgery and ischaemic preconditioning has been increasing. The aim of this study was to evaluate surrogate indicators of haemodynamic, myocardial, and cerebral outcome during off-pump surgery and preconditioning. Haemodynamics and myocardial preservation were monitored in a pilot study of twelve patients undergoing off-pump coronary surgery. Indicators of myocardial metabolism and tissue injury as well as cerebral damage were evaluated in a randomized study of thirty-three patients undergoing on-pump (11) or off-pump surgery with (11) or without (11) preceding myocardial ischaemic preconditioning for five minutes followed by reperfusion for five minutes. The pilot study showed minimal haemodynamic changes and myocardial derangements during off-pump surgery as evaluated intraoperatively based on transcardiac differences of ATP degradation products and lactate and postoperatively based on MB mass of creatine kinase and troponin T. In the following studies, myocardial ischaemic metabolism was evaluated intraoperatively by measuring transcardiac differences of ATP degradation products, lactate, and pH, which increased significantly from the baseline values in all study groups. However, the maximum values of lactate and pH were significantly higher in the cardiopulmonary bypass group (p = 0.02 and p = 0.007, respectively). There were no statistical differences between the preconditioning and non-preconditioning groups. Myocardial tissue injury was evaluated by postoperative leakage of MB mass of creatine kinase and troponin I. Their peak values were significantly higher (p &lt; 0.001 and p = 0.008) after cardiopulmonary bypass (15.1 μg/l and 13.8 μg/l) than after off-pump surgery without preconditioning (6.3 μg/l and 5.2 μg/l). The respective values were 14.8 μg/l and 7.4 μg/l after preconditioning, and there were no statistically significant differences between the off-pump groups with and without preconditioning. Cerebral damage was evaluated based on the intra- and postoperative serum concentrations of neuron-specific enolase, which were corrected with respect to haemolysis. The corrected values were significantly higher after on-pump than off-pump surgery (p = 0.003 and p = 0.005). In conclusion, multi-vessel off-pump coronary artery surgery is a haemodynamically feasible procedure offering better myocardial preservation compared to on-pump surgery. Ischaemic preconditioning of the myocardium does not seem to improve myocardial preservation in off-pump surgery. The slightly lower levels of neuron-specific enolase also suggest less cerebral damage.

Background Chronic Obstructive Pulmonary disease (COPD) is an under-diagnosed disease with a prevalence of approximately 10%, highly dependent on age and smoking habits. Comorbidities are common in COPD and of these, cardiovascular diseases (CVD) are the most common. COPD is the fourth leading cause of death globally, and CVD probably contribute to the high mortality. Within CVD, Ischemic Heart Disease (IHD) is the most common. It is highly clinically relevant to identify signs of ischemic heart disease, other cardiac conditions, and risk factors for CVD in COPD. Electrocardiogram (ECG) is a simple but still major diagnostic tool in clinical cardiology, including disturbances in the electric conduction system and ischemia. Due to the under-diagnosis of COPD, there is limited knowledge regarding the prevalence and prognostic impact of ECG abnormalities in COPD. Arterial stiffness is a risk factor for CVD, which has raised an increased interest, however not evaluated in population based studies of COPD. Aim The overall aim was to describe cardiovascular aspects on COPD, with a specific focus on arterial stiffness, prevalence and prognostic impact of ischemic ECG abnormalities and prolonged QT interval, by comparing subjects with and without obstructive lung function impairment in a population-based cohort. Methods The thesis is based on the Obstructive Lung Disease in Northern Sweden (OLIN) COPD study; a population-based longitudinal cohort study. During the years 2002-2004, all participants in clinical examinations from previously recruited large population-based cohorts were invited to re-examination including spirometry and a structured interview. All subjects with obstructive lung function impairment (n=993) were identified, together with 993 age and sex-matched referents without airway obstruction. The study population (n=1986) has been invited to annual examinations since 2005 including spirometry and structured interview. Papers I-III are based on data from 2005 when electrocardiogram (ECG) was recorded in addition to the basic program. All ECGs were Minnesota coded and QT-time was measured. Paper IV is based data from 2010 when non-invasive measurements of arterial stiffness, assessed as pulse wave velocity (PWV), was added to the program. Spirometric data were classified as normal lung function (NLF), restrictive spirometric pattern (RSP) and airway obstruction (COPD). The following spirometric criteria for COPD were used: post-bronchodilator FEV1/VC&lt;0.70 (papers I-IV, in paper III labelled GOLD-COPD) and lower limit of normal, LLN (LLN-COPD) (paper III). Spirometric classification of COPD severity was based on FEV1 % predicted as a continuous variable or according to the Global Initiative for Obstructive Lung Disease (GOLD), divided into GOLD 1-4. Results The prevalence of ischemic heart disease (IHD), both self-reported and assessed as probable and possible ischemic ECG abnormalities (I-ECG) according to the Whitehall criteria, was similar among subjects with NLF and COPD. The prevalence of both self-reported and probable (I-ECG) according to Whitehall increased by GOLD grade.  Among those with COPD, self-reported IHD was associated with disease severity, assessed as FEV1 % predicted also after adjustment for age and sex (paper I). In both COPD and NLF, those with I-ECG had a higher cumulative mortality over 5 years than those without I-ECG (29.6 vs. 10.6%, p&lt;0.001 and 17.1 vs. 6.3 %, p=0.001). When analysed in a multivariate model, the Mortality Risk Ratio (MRR, 95%CI) was increased for subjects with COPD and I-ECG (2.4, 1.5-3.9), and non-significantly so for NLF with I-ECG (1.65, 0.94-2.90), when compared to NLF without I-ECG.  When analyzed separately among subjects with COPD, the increased risk for death associated with I-ECG persisted independent of age, sex, BMI-class, smoking habits and disease severity assessed as FEV1 % predicted (1.89, 1.20-2.99). The proportion without reported IHD was high among those with I-ECG; 72.4% in NLF and 67.3% in COPD. The pattern was similar also among them; I-ECG was associated with an increased risk for death in COPD and non-significantly so in NLF (paper II). Mean corrected QT-time (QTc) and prevalence of QTc prolongation was higher in RSP than NLF but similar in NLF and GOLD-COPD. The prevalence of borderline as well as prolonged QTc increased by GOLD grade (test for trend p=0.012 for both groups). Of those with GOLD-COPD, 52% fulfilled the LLN-criterion (LLN-COPD). When comparing LLN-COPD and NLF, the pattern was similar as when comparing NLF and GOLD-COPD. The cumulative mortality over 5 years was higher among subjects with borderline and prolonged QTc than those with normal QTc in subjects with GOLD-COPD and LLN-COPD but not in NLF and RSP (paper III). Arterial stiffness, assessed as PWV, was higher in GOLD 3-4 compared to non-COPD (10.52 vs. 9.13 m/s, p=0.042). Reported CVD and age &gt;60 were both associated with significantly higher PWV in COPD as well as in non-COPD. In a multivariate model, GOLD 3-4 remained associated with higher PWV when compared with non-COPD, also when adjusted for sex, age group, smoking habits, blood pressure, reported CVD and pulse rate (paper IV). Conclusion In this population-based study, the prevalence of ischemic ECG abnormalities was similar among subjects with normal lung function and COPD, but increased by disease severity among subjects with COPD. Ischemic ECG abnormalities were associated with an increased mortality among subjects with COPD, independent of common confounders and disease severity, also among those without known heart disease. Whilst the prevalence of QTc prolongation was similar in NLF, COPD and LLN-COPD, it was associated with an increased mortality only in the COPD-groups. ECG is a simple non-invasive method and seems to identify findings of prognostic importance among subjects with COPD. Central arterial stiffness, a known risk factor for cardiovascular disease, was increased among subjects with severe and very severe COPD when compared to subjects without COPD independent of common confounders.