<p>Cerebrovascular disease (stroke), especially ischemic stroke, is a major cause of death and neurological disability in adults. Because of its clinical heterogeneity, stroke is considered as a multi-factorial and polygenic disorder. Most current genetic studies of ischemic stroke focus on genetic susceptibility rather than factors determining stroke outcome. The genetic components of ischemic stroke outcome are difficult to study in humans due to environmental factors and medical intervention. Thus, we proposed to use a surgically induced, permanent, focal cerebral ischemic stroke mouse model to investigate genetic factors of ischemic stroke outcome measured by infarct volume. This model is the middle cerebral artery occlusion (MCAO) model. First, we screened infarct volumes across 32 inbred mouse strains. The infarct volume varies between strains, and this strongly suggests that infarct volume is genetically determined. To identify these genetic factors, we used genome-wide association study [Efficient Mixed-Model Association (EMMA) analysis] on infarct volume from 32 inbred mouse strains. Using the EMMA analysis, we identified 11 infarct volume-associated loci; however, most loci were mapped with missing alleles. This suggests that these loci might be false positives. Thus, we used specifically designed scripts of EMMA analysis with updated mouse SNP database to correct for potential false positives. The loci identified by the updated EMMA analyses will led us to the identification of genes involved in ischemic stroke outcome. </p><p> There are two major mechanisms were proposed to be determinants of infarct volume, the extent of native collateral circulation and neuroprotection. Using the infarct volume screening panel from 32 inbred strains, we observed that infarct volume is inversely correlated with the native collateral vessel number. However, among these inbred strains, we also observed several strains differ significantly in infarct volumes but harbor similar collateral numbers. In order to identify genetic factors determining infarct volume in a collateral-independent manner (neuroprotection), we used quantitative trait locus (QTL) mapping on mouse strains that exhibit the most difference in infarct volumes but the least difference in collateral numbers (C57BL/6J and C3H/HeJ). From the F2 B6 x C3H cross, we mapped 4 loci determining infarct volume (cerebral infarct volume QTL 4 to 7, Civq4 to Civq7). The Civq4 locus is the strongest locus (LOD 9.8) that contributes 21% of phenotypic variance in infarct volume. We also used a parallel F2 B6 x C3H cross to perform a QTL mapping on collateral vessel traits to further verify these collateral-independent loci. Among these 4 loci, the Civq4 and Civq7 loci appear to be truly collateral-independent. Based on strain-specific sequence variants and mRNA expression differences, we proposed Msr1 and Mtmr7 are the potential candidate genes of the Civq4 locus. Identification of the collateral-independent genetic factors will help to understand the genetic architecture, disease pathophysiology and potential therapeutic targets for of ischemic stroke</p> / Dissertation

Les PTM sont une source de douleur régionale et de dysfonctionnements neuromusculaires. Ils sont couramment associés à une hyperalgésie, à des troubles comportementaux et des restrictionsfonctionnelles. La douleur est bien documentée dans la littérature scientifique mais les études de ses conséquences sur le mouvement reposent exclusivement sur l’analyse de gestes simples. L’objectif dece travail est d’étudier la douleur myofasciale du membre supérieur et de vérifier si une technique de thérapie manuelle influençant cette douleur permet de rétablir la performance motrice d’un mouvement fonctionnel. Quatre études ont été réalisées afin d’analyser : 1) la performance motrice d’un mouvement elliptique dans le plan horizontal ; 2) dans le plan frontal et d’une tâche de tapement ; 3) la douleur sur le membre supérieur non atteint chez des sujets ayant subi un AVC ; 4) l’incidence de la douleur chez le personnel soignant d’un centre hospitalier. Les résultats indiquent que la présence de PTM produit la douleur myofasciale et : 1) n’influence pas significativement la performance motrice d’un mouvement elliptique horizontal ; 2) altère la performance motrice d’un mouvement elliptique frontal et d’une tâche de tapement chez les sujets présentant des PTM ; 3) modifie aussi la fonction motrice de l’extrémité supérieure ipsilatérale à la lésion ; 4) touche 8,43% du personnel soignant, étant bilatérale et pouvant conduire à des arrêts maladie dans 14,28 % des cas. L’application d’une technique de compression ischémique locale permet de retrouver la quasi-totalité de la fonction motrice. Il semblerait qu’une reprogrammation du mouvement s’avère nécessaire pour récupérer totalement la fonction motrice. / Myofascial Trigger Points (MTrPs) are source of regional pain and neuromuscular dysfunctions. They are associated to hyperalgesia, psychological disturbances and functional restrictions. Despite myofascial pain has been extensively studied, researches about its influence have only analyzed uniarticular motions. The mains goals of this research were to study the upper limb myofascial pain and to verify whether the application of manual therapy, influencing this pain, could contribute to the motor performance recovery of multiarticular motion. Four studies were carried out in order to analyze: 1) motor performance of an elliptic motion in the horizontal plane, 2) motor performance of an elliptic motion in the frontal plane including an analysis of a tapping task, 3) non-paretic upper limb pain of the stroke patients, 4) myofascial pain incidence at the medical staff in a hospital. The results showed that the presence of TrPs produces myofascial pain. This pain: 1) does not influence significantly the horizontal elliptical motions motor performance, 2) deteriorates the frontal elliptical motions motor performance and the execution of the tapping task, 3) modifies the non-paretic upper limb motor function of the stroke patients, and 4) 8,43 % of medical staff suffers from bilateral myofascial pain, leading to absence at workplace in 14,28% of the cases. The application of local ischemic compression technique allows high recovery of the upper limb motor function. Motor reprogramming therapies could contribute to recover the motor function completely.

Stroke is a common and multifactorial disease influenced by genetic and environmental risk factors. It is a highly heterogeneous entity consisting of two main types, ischemic (80%) and hemorrhagic (20%) stroke. The most common form of hemorrhagic stroke is intracerebral hemorrhage (ICH). Ischemic stroke mainly results from thrombotic or embolic events, while ICH is caused by the rupture of an artery in the brain. The mean age of first-ever stroke is 75 years (73 vs. 78 years, for men and women, respectively) and the age-specific stroke incidence is higher for men as compared to women, suggesting that hormonal factors confer protection. A large body of experimental and observational studies shows that estrogens exert beneficial effects in the cardiovascular system. However, large, recent, clinical randomized trials have failed to demonstrate a lower risk of stroke with hormone replacement therapy (HRT) in elderly postmenopausal women. It is possible that HRT may only protect a subgroup of women. Here, genetic predisposition might be involved. Stroke incidence is 50% higher in northern compared to southern Sweden, suggesting a genetic predisposition in this population. This relatively homogeneous population displays founder effects, making it well suited for genetic studies. Since 1985, the MONICA and VIP projects have conducted large-scale cardiovascular health surveys in this population. Information about conventional stroke risk determinants and also DNA have been collected, and two prospective, nested case-referent cohorts (113 cases and 226 controls; 275 cases and 549 controls) have been sampled. To investigate whether genes of the estrogen signaling system may be important in stroke development, we performed genetic association studies, including specific functional single nucleotide polymorphisms in the genes for estrogen receptor alpha (ERα, ESR1), and its target genes osteoprotegerin (OPG, TNFRS11B) and interleukin-6 (IL-6, IL6). We found a significant association between the common c.454-397T/T genotype in ESR1 and ICH, remaining after adjustments for conventional stroke risk factors. The c.454-397T/T genotype also associated with increased systolic (SBP) and diastolic blood pressure (DBP). The combination of c.454- 397T/T and either hypertension, increased SBP, or increased DBP boosted this association substantially and significant synergistic effects on ICH risk between this genotype and increased blood pressure were demonstrated. In a second study, we found a similar association between the common OPG-1181C/C genotype and ICH. Cognitive impairments, including spatial memory and learning deficiencies, are common after stroke. Estrogens improve cognitive functions, including memory and learning processes, in postmenopausal women and ovariectomized rodents. Post-ischemic housing of rats in an enriched environment (EE) improves recovery of spatial memory and learning impairments. Both estrogen and EE induce neuroplasticity in the hippocampus. We hypothesized that 17β- estradiol combined with EE would accelerate recovery after experimental focal brain ischemia in ovariectomized rats and that such improvements could be related to expression of nerve growth factor-induced gene A (NGFI-A) in the hippocampus. Five to six weeks after middle cerebral artery occlusion, 17β-estradiol–treated rats housed in an EE showed significant improvements in cognitive function (i.e., shorter latency and path in the Morris water maze task) and significantly higher NGFI-A mRNA expression in bilateral cornu ammonis 1 (CA1) and ipsilateral dentate gyrus (DG) compared to placebo-treated animals in EE. In conclusion, we present evidence for the association between polymorphic variants in the ESR1 and TNFRS11B genes and ICH and show that 17β-estradiol in combination with EE accelerates cognitive functions in a rat stroke model, putatively through upregulation of NGFI-A in hippocampal subregions. These findings may contribute to an increased understanding of the underlying genetic etiology of ICH and may be informative for the primary prevention of this disease. They also provide hope for 17β-estradiol combined with early environmental enrichment as a novel therapeutic option following ischemic stroke.

Transient Ischemic Attack (TIA) is a prominent risk factor for subsequent stroke, and its associated morbidity, mortality, and health care costs. Studies have demonstrated up to 80% reductions in subsequent stroke rate with prompt, optimized protocols for rapid TIA evaluation and treatment. National Stroke Association (NSA) and American Heart Association (AHA) guidelines have recommended institution of protocols assuring timely completion of the recommended testing, and evaluation by a stroke expert within 48 hours. However, limited literature exists on the implementation of guideline-based care in rural regions, and the few studies related to TIA suggest that barriers including difficulty accessing services and poorly updated TIA knowledge amongst rural, non-neurologist providers exist despite national guidelines. Behavior change theories have suggested that evaluating factors hindering or motivating behavior change may aid in tailoring implementation of guideline-based practices. This descriptive study sought to understand ED health care providers' perceived barriers to implementation of NSA/AHA TIA guidelines in a rural state. All healthcare providers in each of the state's emergency departments were invited by email to complete an online anonymous survey assessing knowledge of present TIA guidelines and perceived barriers to implementation of these guidelines in their practice setting using a modified Barriers and Facilitators Assessment Instrument (BFAI). After completing the knowledge based questions, respondents were presented a brief educational overview of the guidelines to ensure adequate familiarity with the TIA guidelines to complete the BFAI. Thirty-nine respondents completed the survey. Twenty-seven worked at regional or academic medical centers, and 12 worked at critical access hospitals representing the more rural regions of the state. Consistent with prior work, the most notable finding of this study was a low awareness of the present TIA guidelines amongst ED providers, with none of the survey respondents correctly identifying all items consistent with the evaluation guidelines for TIA. In addition to a low awareness of the guidelines, a number of perceived barriers to implementation were identified, which may inform efforts at implementation, and/or offer a model for similar barrier assessment elsewhere.

We studied Heart Rate Variability (HRV) evolution during therapeutic hypothermia in newborns with hypoxic ischemic encephalopathy (HIE) using spectral analysis. We hypothesized that HRV measures are predictive of neurological outcome in babies with HIE. Non-stationarity in the data causes inaccurate quantification of the spectral power. A modification was proposed to power spectral analysis approach to mitigate the effect of non-stationarity. The modified and the standard approaches were applied to cardiac beat-to-beat intervals of newborns receiving hypothermia treatment. The performance of the approaches in distinguishing the RRi dynamics of two groups of newborns was assessed using area under the receiver operating characteristic (ROC) curve. Our results showed that the modified spectral analysis distinguished the two groups of neonates better than the standard approach. These results may be useful in identifying the deteriorating physiology of the infants receiving hypothermia treatment early in time and strategize alternate interventions for them.

O fenômeno do precondicionamento isquêmico é definido como o aumento da tolerância à isquemia e à lesão de reperfusão, induzida por curtos e sucessivos episódios de isquemia prévios a período de isquemia prolongada. A angina do aquecimento e a de pré-infarto são duas condições clínicas relacionadas ao precondicionamento. Este fenômeno apresenta duas fases distintas, clássica ou precoce e tardia. A atenuação do infradesnível do segmento ST provocada pelo precondicionamento precoce está bem documentada, porém sua expressão cintilográfica permanece controversa. O objetivo desta pesquisa foi avaliar se as atenuações eletrocardiográficas do precondicionamento durante testes sequenciais estão associadas a modificações simultâneas das imagens de cintilografia de perfusão miocárdica em indivíduos com doença coronariana. Vinte e três pacientes foram selecionados entre março de 2009 e julho de 2011. A média de idade foi 64,5 anos (dp=7,0), 19 (82,6%) do sexo masculino e todos tinham lesão coronária em pelo menos um vaso superior a 60%. A medicação antiisquêmica foi suspensa por três a cinco dias. Os pacientes foram submetidos a três testes ergométricos a partir do exame de seleção, sendo dois deles sequenciais e o terceiro realizado após sete dias. A injeção do radiofármaco sestamibi-Tc-99m no teste de precondicionamento e contraprova foi administrado no tempo de aparecimento do infradesnível de ST de -2,0 mm na derivação MC5 e/ou dor precordial anotados no teste inicial ou de seleção. A imagem cintilográfica foi adquirida entre 60 a 90 minutos após o esforço. Os resultados do segundo teste (precondicionamento) mostraram aumento significativo do tempo para o aparecimento da depressão do segmento ST de 1,0 mm (338±130) e 2,0 mm (431±126), em relação ao teste inicial (245±96; 366±103) p<0,001. A diferença na redução do valor máximo de infradesnível de ST entre os três testes foi significativa (3,8±0,8; 2,3±0,6; 3,1±1,0) p<0,001. Houve redução significativa nos escores de perfusão de estresse (p=0,045) entre o primeiro e o segundo testes, bem como para o escore da diferença entre o estresse e repouso (p= 0,03), sem diferença na extensão da área de isquemia entre as três etapas detectadas pela cintilografia (p=0,691). Em conclusão, houve redução significativa das alterações eletrocardiográficas induzidas pelo precondicionamento isquêmico precoce em maior proporção do que as observadas nas respectivas imagens de cintilografia de perfusão miocárdica; não se observou associação entre a redução da depressão do ST e a redução do escore de perfusão na fase de precondicionamento, nem correlação entre a magnitude do infradesnível máximo de ST e a redução do escore de perfusão (r=0,07 e p=0,75). / The phenomenon of ischemic preconditioning is defined as the increase of tolerance to ischemia and injury of reperfusion induced by short and consecutive episodes of isquemia prior to prolonged arterial occlusion. Warm-up and pre-infarction angina are two clinical conditions regarding this phenomenon. The ischemic preconditioning has two distinct windows designed as classical and late. The improvement of ST depression induced by classical preconditioning is well documented, however its scintigraphy expression is still controversial. The aim of this research was to assess whether the reduction of ST depression induced by preconditioning during these sequencial exercise testing are associated to simultaneous alterations of the scintigraphy images of myocardial perfusion in individuals with coronary artery disease. From March 2009 to July 2011, 23 patients were selected, mean age 64,5 (sd=7,0), 19(82,6%) male. All patients had coronary artery stenosis at least 60% in one vessel. The anti ischemic therapy was discontinued for three days. Patients underwent three exercises testing after screening process; two of these tests were in a sequence and the other one performed after seven days. Tc-99m-sestamibi radiotracer injection was applied in the preconditioning test as well as for the third test at the time of development of ST depression 2,0 mm in the CM5 lead and/or chest pain estabilished in the screening process or first test. The scintigraphy image was obtained from 60 to 90 minutes after exertion. The results of the preconditioning test showed a significant increase of time for manifestation of the ST depression 1,0 mm (338±130) and 2,0 mm (431±126) regarding the first test (245±96; 366±103), p<0,001. There was a significant difference in the decrease of maximum value of ST depression among the three tests (3,8±0,8; 2,3±0,6; 3,1±1,0), p<0,001. A significant reduction in stress perfusion score (p=0,045) occurred between the first and second test as well as for the difference score between stress and rest (p=0,03). However, there was not a significant difference in the total defect size among the three stages detected by myocardial scintigraphy (p=0,691). In conclusion, there was a significant decrease of electrocardiographic alterations resulting from early preconditioning in greater proportion than the observed in scintigraphy images. It was not observed an association between the decrease of ST depression with the stress perfusion score during the preconditioning period nor the correlation between the magnitude of the maximum value of ST depression and the decrease of perfusion score (r=0,07 and p=0,75).

INTRODUÇÃO: A encefalopatia hipóxico-isquêmica (EHI) corresponde a uma das maiores causas de morbidade e mortalidade neonatal. Ocorre em consequência à asfixia perinatal aguda, representada por baixo escore de Apgar e evidências de distúrbios neurológicos ao nascimento. A hipotermia terapêutica (HT) tem mostrado benefícios relevantes no prognóstico neurológico a longo prazo, por reduzir o metabolismo cerebral, retardando o início da despolarização hipóxica celular. Os efeitos da HT no sistema cardiovascular foram pouco estudados, suscitando questionamentos quanto à adequada interpretação dos achados ecocardiográficos nesta condição terapêutica. OBJETIVO: avaliar o comportamento hemodinâmico e da função ventricular de recém-nascidos com EHI na vigência de HT, utilizando-se técnicas ecocardiográficas convencionais e avançadas. MÉTODO: trata-se de um estudo observacional desenvolvido em três instituições, em que 22 recém-nascidos com EHI foram avaliados por meio da ecocardiografia nas duas fases da HT (durante a hipotermia e após o reaquecimento). O grupo controle foi composto por 22 recém-nascidos saudáveis. Os bebês foram submetidos a HT seguindo critérios do protocolo de hipotermia de cada um dos serviços. RESULTADOS: Função ventricular esquerda: as frações de ejeção (FE) e de encurtamento foram maiores após o reaquecimento (74 ± 5% e 41 ± 5% respectivamente) em relação ao grupo controle (70 ± 5%, p = 0,003 e 37 ± 4%, p = 0,002). O índice de performance miocárdica (IPM) do ventrículo esquerdo (VE) avaliado pelo Doppler pulsado se manteve constante nas duas fases da HT (0,51 ± 0,13, hipotermia = reaquecimento) e foi menor na comparação destas com o grupo controle (0,63 ± 0,18, p = 0,02). Os valores do strain circunferencial e radial, do twist, da torção e do strain longitudinal global do VE (STLGLVE) foram semelhantes entre o grupo controle e o grupo estudo, tanto durante a hipotermia quanto após o reaquecimento. Função ventricular direita: Observou-se incremento da velocidade da onda s´ do ventrículo direito (VD) após o reaquecimento (de 0,07 ± 0,02 m/s durante a hipotermia para 0,09 ± 0,01 m/s, p < 0,001), sendo esta também mais elevada quando comparada aos valores do grupo controle (0,07 ± 0,01 m/s, p < 0,001). Houve queda dos valores da variação fracional das áreas (FAC) do VD após o reaquecimento (38 ± 11% durante a hipotermia, 36 ± 11% após o reaquecimento e 43 ± 10% grupo controle), com diferenças significativas entre esses dois últimos (p = 0,03). Quanto ao IPM do VD, o grupo controle apresentou médias menores (0,29 ± 0,13) que o grupo caso durante a hipotermia (0,46 ± 0,33, p = 0,03). O strain longitudinal global do VD (STLGLVD) foi significativamente pior tanto durante a hipotermia (-18 ± -5%, p = 0,02) quanto após o reaquecimento (-18 ± 4%, p = 0,01) quando comparados ao grupo controle (-21 ± 2%). Parâmetros hemodinâmicos: A pressão sistólica na artéria pulmonar foi mais elevada no grupo estudo durante as duas fases do tratamento (hipotermia 45 ± 24 mmHg, p = 0,02 e reaquecimento 53 ± 34 mmHg, p = 0,01 versus grupo controle 29 ± 11 mmHg). A FC foi significativamente mais baixa durante a hipotermia comparada ao período após o reaquecimento (FC 111 ± 19 bpm versus 144 ± 20 bpm, p < 0,001) e ao grupo controle (FC 130 ± 16 bpm, p < 0,001). Durante o reaquecimento, observou-se elevação do débito cardíaco (DC) esquerdo e direito em relação ao período de hipotermia (DC esquerdo 214 ± 39 ml/kg/min versus 155 ± 47 ml/kg/min, p < 0,001; DC direito 369 ± 141 ml/kg/min versus 269 ± 113 ml/Kg/min, p = 0,005) sendo significativamente mais elevado que no grupo controle (DC Esquerdo 174 ± 47 ml/kg/min, p = 0,004 e DC direito 288 ± 74 ml/Kg/min, p = 0,02). CONCLUSÕES: A função ventricular esquerda permanece estável nas duas fases da HT, demonstrando o baixo comprometimento cardíaco esquerdo do resfriamento induzido. Os valores da FE, da fração de encurtamento e da onda s´ do VD, maiores após o reaquecimento, podem ser consequentes a um estado hiperdinâmico do coração. Disfunção ventricular direita foi observada nos momentos em que a pressão pulmonar estava elevada. O STLGLVD foi a única ferramenta capaz de identificar o comprometimento da função sistólica do VD durante a HT. / INTRODUCTION: The hypoxic-ischemic encephalopathy (HIE) corresponds to one of the biggest causes of neonatal morbidity and mortality. It occurs in consequence to acute perinatal asphyxia, represented by low Apgar score and evidences of neurological disorders in birth. The therapeutic hypothermia (TH) has shown significant benefits in long term neurological prognosis, by reducing the cerebral metabolism, delaying the onset of the hypoxic depolarization in cellular level. The TH effects in cardiovascular system have been insufficiently researched, raising questions regarding the adequate reading of the echocardiographic results in this condition. OBJECTIVE: to evaluate the hemodynamic and the ventricular performance of neonates with HIE submitted to TH, using conventional and advanced echocardiographic techniques. METHODS: this research is an observational study developed in three institutions, in which 22 neonates with HIE were evaluated by echocardiography in the two phases of TH (during hypothermia and after rewarming). The control group was composed by 22 healthy neonates. The infants were submitted to TH following hypothermia protocol criteria of each services. RESULTS: Left ventricular function: the ejection fraction (EF) and the shortening fraction were higher after rewarming (74 ± 5% and 41 ± 5% respectively) compared to the control group (70 ± 5%, p = 0.003 and 37 ± 4%, p = 0.002). The myocardial performance index (MPI) of the left ventricle (LV), evaluated by pulsed wave Doppler, remained constant in the two phases of TH (0.51 ± 0.13, hypothermia = rewarming) and this MPI was lower in comparison to the control group (0.63 ± 0.18, p = 0.02). The values of the circumferential and radial strain, the twist, the torsion and the global longitudinal strain (GLS) of the LV were similar between the control group and the study group, as during hypothermia as after rewarming. Right ventricular function: it was noted increment of the right ventricle (RV) s´ wave velocity after rewarming (from 0.07 ± 0.02 m/s during hypothermia to 0.09 ± 0.01 m/s, p < 0.001), also it was higher when compared to the control group (0.07 ± 0.01 m/s, p < 0.001). There was decrease of the RV fractional area change (FAC) values after rewarming (38 ± 11% during hypothermia, 36 ± 11% after rewarming and 43 ± 10% in control group), with significant differences between these two last values (p = 0.03). Regarding RV\'s MPI, the control group presented lower averages (0.29 ± 0.13) than the case group during hypothermia (0.46 ± 0.33, p = 0.03). The RV GLS was worse as during hypothermia (-18 ± -5%, p = 0.02) as after rewarming (-18 ± 4%, p = 0.01) when compared to the control group (-21 ± 2%). Hemodynamic parameters: The pulmonary artery systolic pressure was higher in the study group during the two phases of the treatment (hypothermia 45 ± 24 mmHg, p = 0.02 and rewarming 53 ± 34 mmHg, p = 0.01 versus control group 29 ± 11 mmHg). The heart rate (HR) was significantly lower during hypothermia compared to the after rewarming period (HR 111 ± 19 bpm versus 144 ± 20 bpm, p < 0.001) and to the control group (HR 130 ± 16 bpm, p < 0.001). After rewarming it was seen increase of the left and right cardiac output (CO) compared to the hypothermia period (left CO 214 ± 39 ml/kg/min versus 155 ± 47 ml/kg/min, p < 0.001; right CO 369 ± 141 ml/kg/min versus 269 ± 113 ml/Kg/min, p = 0.005), remaining significantly higher than in the control group (left CO 174 ± 47 ml/kg/min, p = 0.004 and right CO 288 ± 74 ml/Kg/min, p = 0.02). CONCLUSIONS: The LV function remains stable in the two phases of TH, showing low left cardiac impairment of the induced cooling. The values of EF, shortening fraction and RV s´ wave were higher after rewarming, possibly due to a hyperdynamic heart state. A right ventricular dysfunction was observed when the pulmonary artery systolic pressure was high. The RV GLS was the only tool able to identify the RV systolic impairment during TH.

INTRODUÇÃO: A asfixia perinatal é uma das principais causa de óbito nos recémnascidos (RN) de termo acima de 2500g no Brasil, sendo também a causa mais importante de encefalopatia e lesão cerebral permanente em crianças. Não existindo ainda um consenso acerca de qual seria o melhor critério para seu diagnóstico. OBJETIVOS: Verificar a prevalência de asfixia e de encefalopatia hipóxico-isquêmica segundo dois critérios diagnósticos, avaliar influência do tipo de parto e a evolução neurológica. MÉTODO: Corte transversal prospectivo, onde foram incluídos 30 recém-nascidos que apresentaram asfixia segundo dois critérios diagnósticos: critério 1 foi preconizado pela AAP/ACOG de 1996 (pH de cordão 7,0, disfunção múltipla de órgãos, manifestações neurológicas na primeira semana de vida além do Apgar entre 0-3 no quinto minuto); o critério 2 foi de Buonocore em 2002, modificado (pH de cordão 7,2, Apgar de 4-6 no quinto minuto e necessidade de fração de oxigênio inspirada 0,40 manter saturação de 86%); num período de dois anos (2004/2006) sendo excluídos aqueles que pudessem apresentar encefalopatia por outras causas como malformações, infecções congênitas, erro inato do metabolismo. Para realizar o diagnóstico foram colhida gasometria de cordão dos recémnascidos a termo que apresentaram Apgar de quinto minuto 6 e feitas provas de função cardíaca, hepática, renal e controle hematológico além da avaliação neurológica pelos critérios clínicos de Sarnat e Sarnat de 1976, para verificar o grau de encefalopatia. RESULTADOS: Durante este período a prevalência observada de asfixia foi de 3,2 por 1000 nascimentos a termo (IC a 95% - [2,1 por mil; 4,5 por mil]) e de encefalopatia de 1,7 por 1000 nascimentos a termo (IC a 95% - [0,8 por mil; 2,5 por mil]). A taxa de mortalidade foi de 16,7% e 36,7% evoluíram com encefalopatia grave. Não houve correlação estatística da asfixia e nem da encefalopatia quanto às características maternas, exceto uma tendência maior nas nulíparas e primíparas com parto normal. Quanto à indicação do parto 46,7% apresentava trabalho de parto sem intercorrências, mas pelo critério 1 houve maior número com sofrimento fetal relacionado à maior gravidade da asfixia. O sexo mais freqüente foi o masculino e em ambos os grupos apresentaram acidose metabólica e respiratória e alterações enzimáticas principalmente cardíacas e hepáticas e, função renal com aumento da creatinina. Foi observado que para Sarnat estágios 1 e 2, leve e moderada, houve uma maior proporção de recém-nascidos no critério 2 enquanto que para o Sarnat estágio 3, grave, a maior proporção foi com o critério 1 Resumo (p = 0,016). Enquanto o Apgar de primeiro minuto não mostrou correlação com a gravidade da encefalopatia, 85% dos recém-nascidos com encefalopatia leve/moderada tiveram Apgar de quinto minuto entre 4-6 e a maioria com quadro grave o Apgar foi entre 0-3 (p = 0,018). Houve uma tendência de acordo com o aumento da gravidade da encefalopatia a uma redução do dióxido de carbono sanguíneo, bicarbonato e aumento negativo do excesso de base além do aumento de enzima cardíaca (creatina fosfoquinase), mas não foi estatisticamente significante. CONCLUSÃO: Não houve correlação estatística entre asfixia e a gravidade da encefalopatia com fatores maternos. Todos os recém-nascidos apresentaram acidose respiratória e metabólica e entre as alterações enzimáticas cardíacas foram as mais importante. Em relação ao índice de Apgar, a nota de quinto minuto mostrou melhor correlação com a gravidade evolutiva dos pacientes. Com o critério 1 (Academia Americana de Pediatria) houve melhor correlação com a mortalidade, no entanto por ser muito rigoroso acaba por excluir recém-nascidos que evoluem com quadros de encefalopatia grave / INTRODUCTION: The perinatal asphyxia is one of the main causes of death in newborns and also the most important cause of encephalopathy and permanent cerebral lesion in children. OBJECTIVES: To check the prevalence of asphyxia and of hypoxic-ischemic encephalopathy in term newborns, using two diagnostic criteria; to assess whether the diagnostic criterion used and the type of obstetric assistance are related to the grade of seriousness of the asphyxia and of the encephalopathy. Methods: Prospective transversal cut study carried out in a public hospital in the East Zone of São Paulo, in which 30 term newborns with perinatal asphyxia were included and classified in two groups, according to two diagnostic criteria adopted: criterion 1 recommended by American Academy of Pediatrics (1996), and which considers as bearer of perinatal asphyxia the newborn presenting: cord pH 7.0, multiple organ dysfunction, neurological manifestations in the first week of life and Apgar value in the fifth minute of life between 0-3. Criterion 2 defined by Buonocore in 2002 and which consists in: cord pH 7.2, Apgar value in the fifth minute of life between 4-6 and fraction inspired of oxygen need 0.40 to maintain a saturation of 86%. To confirm the diagnosis, the following laboratorial examinations were carried out: gasometry, hepatic, renal and cardiac function tests, besides the hematological control. To assess the neurological function and verify the grade of hypoxic-ischemic encephalopathy, the clinical criteria of Sarnat and Sarnat were used. RESULTS: The prevalence of perinatal asphyxia observed in this case was of 3.2 per 1,000 term births (IC at 95% - [2.1 per one thousand; 4.5 per one thousand]) and of hypoxic-ischemic encephalopathy was of 1.7 per 1,000 term births (IC at 95% - [0.8 per one thousand; 2.5 per one thousand]). As regards the criteria used, the newborns of criterion 1 statistically presented more fetal suffering when compared to those of criterion 2, and this fact was also related to the grade of seriousness of the asphyxia. The newborns of the two groups presented cardiac changes with elevation of the specific enzyme, hepatic changes with elevation of the glutamic pyruvic and oxaloacetic transaminases and renal changes proven by elevation of creatinine, besides the relevant respiratory and metabolic acidosis. The newborns with serious metabolic acidosis and high levels of creatine phosphokinase had a greater degree of neurological impairment. In 85% of newborns with light/moderate encephalopathy was verified an Apgar value at fifth minute of life between 4-6, and in newborns with serious encephalopathy this value was between 0-3 (p = 0.018). A positive trend for Summary the presence of asphyxia and encephalopathy was found in children of primiparous mothers and born during normal parturition. When assessing the degree of neurological impairment through the criteria of Sarnat and Sarnat, A greater proportion of newborns of criterion 2 were found in the lighter degrees. In degree 3, which is the most serious, a greater proportion of newborns of criterion 1 (p = 0,016) was found. The mortality rate in these cases was of 16.7%, and most of the newborn were of criterion 1. CONCLUSION: The prevalence of perinatal asphyxia and hypoxic -ischemic encephalopathy is as mentioned in the world literature, and smaller than found in Brazil. Criterion 1 was the one that showed a better correlation with the mortality of patients. However, as it is too rigorous, it may exclude the newborn that survive and develop hypoxic-ischemic encephalopathy. As regards the type of obstetric assistance, despite the fact that no statistically significant difference was observed, there was a positive trend to the presence of asphyxia and encephalopathy in children of primiparous mothers born during normal parturition

INTRODUÇÃO E HIPÓTESE: A epinefrina é um potente vasoconstritor com efeitos inotrópico e arritmogênico, é utilizada em protocolos de reanimação cardiopulmonar e como fármaco de primeira escolha em alguns casos de choque. Contudo, o seu uso pode ser seguido por lesões do miocárdio e disfunção cardíaca. Modelos experimentais têm mostrado efeitos cardioprotetores do fentanil por meio de mecanismos antiarrítmicos e anti-isquêmicos. O objetivo deste estudo foi avaliar o efeito cardioprotetor do fentanil em suínos expostos a altas doses de epinefrina. MÉTODOS: Após aprovação do comitê de ética institucional, 26 porcos Large White e Landrace foram alocados aleatoriamente em três grupos: grupo fentanil (n = 10), no qual os porcos receberam 20 ug/kg de fentanil 5 minutos antes de 5 doses de 20 ug/kg de epinefrina, as quais foram intercaladas por intervalos de 5 minutos entre cada dose; grupo salina (n = 10), no qual os porcos receberam solução salina volume-equivalente ao fentanil 5 minutos antes das 5 doses de epinefrina e grupo Sham (n = 6), que não recebeu fentanil ou epinefrina. Foram coletadas variáveis hemodinâmicas, ecocardiográficas, gasométricas e marcadores cardíacos durante as 6 horas de experimento. Ao final do estudo, o coração e os pulmões dos porcos foram removidos para análise por microscopia óptica, microscopia eletrônica e imuno-histoquímica (caspase-3). Os dados foram analisados usando equações de estimação generalizadas (GEE) e a significância estatística foi estabelecida em p < 0,05. RESULTADOS: Os níveis de troponina-I entre os grupos foram inicialmente equivalentes. Ao final do experimento, foi observado menor nível de troponina-I no grupo fentanil, em comparação com o grupo salina (1,91 ± 1,47 versus 5,44 ± 5,35 ng.ml-1, p = 0,019). Adicionalmente, a microscopia eletrônica e a imunohistoquímica demonstraram menor lesão miocárdica no grupo fentanil. Não houve diferença significativa entre o grupo fentanil e o salina para as variáveis hemodinâmicas, ecocardiográficas e gasométricas. CONCLUSÃO: O fentanil promove cardioproteção aos efeitos de altas doses de epinefrina sem prejudicar o efeito hemodinâmico da mesma / INTRODUCTION AND HYPOTHESIS: Epinephrine is a powerful vasopressor with inotropic and arrhythmogenic effects that is used in cardiopulmonary resuscitation protocols and as first choice drug in some cases of shock. However, its use could be followed by myocardial injury and dysfunction. Experimental models have shown cardioprotective effects of fentanyl through antiarrhythmic and anti-ischaemic mechanisms. The objective of this study was to evaluate the cardioprotective effect of fentanyl on myocardial function in swine exposed to high doses of epinephrine. METHODS: After institutional ethics committee approval, twenty-six Large White and Landrace pigs were allocated randomly into three groups: Fentanyl group (n=10), which received 20ug/kg of fentanyl five minutes before five doses of 20ug/kg of epinephrine interspersed with 5 minute intervals between each dose; Saline group (n=10), which received saline in a volume-equivalent manner of fentanyl five minutes before 20ug/kg of epinephrine doses; and Sham group (n=6), which did not receive fentanyl nor epinephrine. We assessed hemodynamics, transesophageal echocardiography, cardiac markers, and gasometry for 6 h. At the end of the experiment, the heart and lungs were removed for analysis by optical and electron microscopy and immunohistochemical (Caspase-3) assay. Data was analyzed using generalized estimating equations (GEE) and statistical significance was assumed at p < 0.05. RESULTS: Troponin levels among the groups were initially equivalent. Fentanyl group showed lower levels of troponin at the end of the sixth hour compared to the saline group (1.91 ± 1.47 vs. 5.44 ± 5.35 ng.mL-1, p=0.019). There were no significantly difference between fentanyl and saline group for hemodynamic, echocardiographic and gasometrical data. Transmission electron microscopy and immunohistochemistry also showed less myocardial injury in the fentanyl group. CONCLUSION: We concluded that fentanyl promotes effective cardioprotection to high-dose epinephrine without blunting the hemodynamic effect of epinephrine

Made available in DSpace on 2016-04-27T18:47:18Z (GMT). No. of bitstreams: 1 Dissertacao Ana Claudia Gomes.pdf: 285611 bytes, checksum: b837fc73ac49097ed9faeb3a2e1c4bf1 (MD5) Previous issue date: 2006-02-16 / This study has as objective to verify the mental and compartmental state, and elderly subjects functionality and social interaction that underwent a right ischemic cerebral vascular accident (AVCID). The research was accomplished through studying four patients after suffering AVCID, among them, three were women and one man, aged between 60 to 70 years old. The profile of each one was verified and analyzed through an identification questionnaire, then, it was applied other six questionnaires directed to cognitive, compartmental, mood functionality and also social analyses. To accomplish this study, it was used the qualitative and descriptive methodology. This methodology was applied and used to describe and analyze all the studied subject subjectivity. Among the results obtained it was pointed out the motor implication of the left hemi body from all subjects, with damage on its functionality mainly in accomplishing tasks, few cognitive changes, besides affective and social changes. The physiotherapist treatments accomplished by a professional interested and also offer a more consistent psychological support can propitiate motor and functional progress reached faster. However the sequels and physical limitations caused by AVC resound intensively on each elderly subject studied, altering his daily life and his life quality / Este estudo teve como objetivo verificar o estado mental, comportamental, a funcionalidade e a interação social de indivíduos idosos que sofreram acidente vascular cerebral isquêmico direito (AVCID). Participaram da pesquisa quatro pacientes após o AVCID, entre os quais três eram mulheres e um homem, com idade variando entre 60 e 70 anos. O perfil de cada um deles foi verificado e analisado através de um questionário de identificação, e em seguida, foram aplicados outros seis questionários direcionados à análise cognitiva, comportamental, de humor, de funcionalidade e também social. Para a realização do estudo, utilizou-se a metodologia qualitativa e descritiva. Essa metodologia foi aplicada e usada para descrever e analisar toda a subjetividade dos sujeitos estudados. Entre os resultados obtidos salientaram-se o comprometimento motor do hemicorpo esquerdo de todos os indivíduos, com prejuízo de sua funcionalidade principalmente na realização de tarefas, poucas alterações cognitivas, além de alterações afetivas e sociais. O tratamento fisioterápico realizado por um profissional interessado em também oferecer apoio psicológico e social mais consistente poderá propiciar progressos motores e funcionais mais rapidamente alcançados. No entanto as seqüelas e limitações físicas provocadas pelo AVC repercutiram intensamente na vida de cada um dos idosos estudados, alterando seu cotidiano e sua qualidade de vida.