Avaliação da expressão de mediadores imunitários em amostras de cetáceos capturados acidentalmente em Portugal Continental

Dissertação de Mestrado Integrado em Medicina Veterinária

Immune cell changes in swimmers : response to acute exercise and training

O treino competitivo envolve exercício intenso e prolongado, capaz de modular o número e actividade das células imunitárias. Quando demasiado exigente poderá induzir fadiga e aumentar a susceptibilidade a doenças. Esta dissertação apresenta três estudos desenvolvidos no âmbito da Imunologia do Exercício, considerando a análise da resposta celular imunitária sistémica aguda e crónica ao exercício aplicada em situações reais do treino competitivo de natação, controlando factores passíveis de influenciar esta resposta. Pretendeu-se avaliar a resposta imunitária a uma sessão de treino prolongada e intensa, durante as 24h de recuperação (Estudo 1) e a uma época de treino com sete meses (Estudo 2), e estudar a influência de um macrociclo de treino de quatro meses sobre a resposta imunitária à mesma sessão de treino e período de recuperação (Estudo 3), controlando sexo, fases do ciclo menstrual, maturidade, escalão, especialidade, performance, cargas de treino e sintomas respiratórios superiores (URS). A sessão de treino induziu a diminuição da vigilância imunitária adquirida imediatamente e, pelo menos nas 2h seguintes. Juvenis e seniores recuperaram totalmente 24h depois, mas não os juniores, reforçando a ideia da existência de uma janela aberta para a infecção após exercícios prolongados e intensos e sugerindo uma recuperação menos eficiente para os juniores. No período de treino mais intenso da época observou-se uma imunodepressão e maior prevalência de URS. No final da época, a imunidade inata diminuiu aparentando maior sensibilidade aos efeitos cumulativos da carga de treino, enquanto a imunidade adquirida parece ter recuperado após o taper. O macrociclo de treino atenuou a resposta imunitária à sessão de treino e aumentou o período de janela aberta às infecções (efeitos mais acentuados nos adolescentes). Os resultados evidenciam a importância de controlar alterações imunitárias durante a época competitiva, especialmente em períodos de treino intenso e quando se realizam sessões de treino intensas consecutivas com recuperações inferiores a 24h.

Análise inicial do uso de enxerto tubular orgânico L-D-Hydro - (Eato L-D-Hydro) para realização de Blalock-Taussig modificado nas cardiopatias congênitas com hipofluxo pulmonar

OBJETIVO: Analisar os resultados iniciais da utilização do enxerto tubular orgânico, utilizados para anastomoses sistêmico-pulmonares. MÉTODOS: De março/2002 a abril/2003, 10 pacientes foram submetidos à realização de shunt sistêmico pulmonar tipo Blalock-Taussig modificado utilizando um novo tipo de enxerto biológico originado da artéria mesentérica bovina tratada com poliglicol denominado L-D-Hydro. A idade variou de 3 dias a 7 anos e 60% dos pacientes eram do sexo masculino. O diagnóstico das cardiopatias foi determinado pela ecocardiografia, todos apresentando sinais clínicos de hipóxia severa (cianose). As cardiopatias foram: tetralogia de Fallot (40%), atresia tricúspide (50%), defeito do septo atrioventricular (10%). RESULTADOS: Em 10 pacientes, ocorreu um óbito por sepse e em nove houve melhora imediata na saturação de O2 ao oxímetro de pulso e da pressão parcial de oxigênio à gasometria arterial. Nenhum paciente apresentou obstrução do shunt no pós-operatório imediato ou qualquer outra complicação. Todos os pacientes mostraram shunt pérvio ao exame ecocardiográfico no pós-operatório imediato e tardio, realizado no 3º mês de pós-operatório. Nenhum paciente apresentou sangramento no intra e pós-operatório. CONCLUSÃO: O enxerto tubular L-D-HYDRO demonstrou ser promissor para a realização de shunt sistêmico pulmonar, como alternativa para produtos inorgânicos existentes no mercado, entretanto, temos de ter maior número de implantes e acompanhamento tardio para uma avaliação definitiva.

Utilização de terapêuticas comprovadamente úteis no tratamento da coronariopatia aguda: comparação entre diferentes regiões brasileiras. Análise do Registro Brasileiro de Síndromes Coronarianas Agudas (BRACE - Brazilian Registry on Acute Coronary Syndromes)

FUNDAMENTO: Pouco se sabe, em nosso meio, sobre diferenças regionais no tratamento da coronariopatia aguda. OBJETIVO: Analisar o comportamento regional relativamente à utilização de terapêuticas comprovadamente úteis na coronariopatia aguda. MÉTODOS: Foram selecionados aleatoriamente 71 hospitais, respeitando-se a proporcionalidade do país em relação à localização geográfica, entre outros critérios. Na população global, foi analisada regionalmente a utilização de AAS, clopidogrel, inibidor da ECA/bloqueador de AT1, betabloqueador e estatina, isoladamente e agrupados por escore individual que variou de 0 (nenhum medicamento utilizado) a 100 (todos utilizados). No infarto com supradesnivelamento de ST (IAMCSST) foram analisadas diferenças regionais sobre utilização de terapêuticas de recanalização (fibrinolíticos e angioplastia primária). RESULTADOS: No global da população, nas primeiras 24 horas de hospitalização, a média de escore na região Norte-Nordeste (70,5 ± 22,1) foi menor (p < 0,05) do que nas regiões Sudeste (77,7 ± 29,5), Centro-Oeste (82 ± 22,1) e Sul (82,4 ± 21). Por ocasião da alta, o escore da região Norte-Nordeste (61,4 ± 32,9) foi menor (p < 0,05) do que nas regiões Sudeste (69,2 ± 31,6), Centro-Oeste (65,3 ± 33,6), e Sul (73,7 ± 28,1); adicionalmente, o escore do Centro-Oeste foi menor (p < 0,05) do que o do Sul. No IAMCSST, o uso de terapêuticas de recanalização foi maior no Sudeste (75,4%, p = 0,001 em relação ao restante do país), e menor no Norte-Nordeste (52,5%, p < 0,001 em relação ao restante do país). CONCLUSÃO: O uso de terapêuticas comprovadamente úteis no tratamento da coronariopatia aguda está aquém do desejável no país, com importantes diferenças regionais.

Impact of Different Obesity Assessment Methods after Acute Coronary Syndromes

Background: Abdominal obesity is an important cardiovascular risk factor. Therefore, identifying the best method for measuring waist circumference (WC) is a priority. Objective: To evaluate the eight methods of measuring WC in patients with acute coronary syndrome (ACS) as a predictor of cardiovascular complications during hospitalization. Methods: Prospective study of patients with ACS. The measurement of WC was performed by eight known methods: midpoint between the last rib and the iliac crest (1), point of minimum circumference (2); immediately above the iliac crest (3), umbilicus (4), one inch above the umbilicus (5), one centimeter above the umbilicus (6), smallest rib and (7) the point of greatest circumference around the waist (8). Complications included: angina, arrhythmia, heart failure, cardiogenic shock, hypotension, pericarditis and death. Logistic regression tests were used for predictive factors. Results: A total of 55 patients were evaluated. During the hospitalization period, which corresponded on average to seven days, 37 (67%) patients had complications, with the exception of death, which was not observed in any of the cases. Of these complications, the only one that was associated with WC was angina, and with every cm of WC increase, the risk for angina increased from 7.5 to 9.9%, depending on the measurement site. It is noteworthy the fact that there was no difference between the different methods of measuring WC as a predictor of angina. Conclusion: The eight methods of measuring WC are also predictors of recurrent angina after acute coronary syndromes.

Validation of the Killip-Kimball Classification and Late Mortality after Acute Myocardial Infarction

Background: The classification or index of heart failure severity in patients with acute myocardial infarction (AMI) was proposed by Killip and Kimball aiming at assessing the risk of in-hospital death and the potential benefit of specific management of care provided in Coronary Care Units (CCU) during the decade of 60. Objective: To validate the risk stratification of Killip classification in the long-term mortality and compare the prognostic value in patients with non-ST-segment elevation MI (NSTEMI) relative to patients with ST-segment elevation MI (STEMI), in the era of reperfusion and modern antithrombotic therapies. Methods: We evaluated 1906 patients with documented AMI and admitted to the CCU, from 1995 to 2011, with a mean follow-up of 05 years to assess total mortality. Kaplan-Meier (KM) curves were developed for comparison between survival distributions according to Killip class and NSTEMI versus STEMI. Cox proportional regression models were developed to determine the independent association between Killip class and mortality, with sensitivity analyses based on type of AMI. Results: The proportions of deaths and the KM survival distributions were significantly different across Killip class >1 (p <0.001) and with a similar pattern between patients with NSTEMI and STEMI. Cox models identified the Killip classification as a significant, sustained, consistent predictor and independent of relevant covariables (Wald χ2 16.5 [p = 0.001], NSTEMI) and (Wald χ2 11.9 [p = 0.008], STEMI). Conclusion: The Killip and Kimball classification performs relevant prognostic role in mortality at mean follow-up of 05 years post-AMI, with a similar pattern between NSTEMI and STEMI patients.

Do Diabetic Patients with Acute Coronary Syndromes Have a Higher Threshold for Ischemic Pain?

Background: Data from over 4 decades have reported a higher incidence of silent infarction among patients with diabetes mellitus (DM), but recent publications have shown conflicting results regarding the correlation between DM and presence of pain in patients with acute coronary syndromes (ACS). Objective: Our primary objective was to analyze the association between DM and precordial pain at hospital arrival. Secondary analyses evaluated the association between hyperglycemia and precordial pain at presentation, and the subgroup of patients presenting within 6 hours of symptom onset. Methods: We analyzed a prospectively designed registry of 3,544 patients with ACS admitted to a Coronary Care Unit of a tertiary hospital. We developed multivariable models to adjust for potential confounders. Results: Patients with precordial pain were less likely to have DM (30.3%) than those without pain (34.0%; unadjusted p = 0.029), but this difference was not significant after multivariable adjustment, for the global population (p = 0.84), and for subset of patients that presented within 6 hours from symptom onset (p = 0.51). In contrast, precordial pain was more likely among patients with hyperglycemia (41.2% vs 37.0% without hyperglycemia, p = 0.035) in the overall population and also among those who presented within 6 hours (41.6% vs. 32.3%, p = 0.001). Adjusted models showed an independent association between hyperglycemia and pain at presentation, especially among patients who presented within 6 hours (OR = 1.41, p = 0.008). Conclusion: In this non-selected ACS population, there was no correlation between DM and hospital presentation without precordial pain. Moreover, hyperglycemia correlated significantly with pain at presentation, especially in the population that arrived within 6 hours from symptom onset.

Left Atrial Volume Index and Prediction of Events in Acute Coronary Syndrome: Solar Registry

Background: According to some international studies, patients with acute coronary syndrome (ACS) and increased left atrial volume index (LAVI) have worse long-term prognosis. However, national Brazilian studies confirming this prediction are still lacking. Objective: To evaluate LAVI as a predictor of major cardiovascular events (MCE) in patients with ACS during a 365-day follow-up. Methods: Prospective cohort of 171 patients diagnosed with ACS whose LAVI was calculated within 48 hours after hospital admission. According to LAVI, two groups were categorized: normal LAVI (≤ 32 mL/m2) and increased LAVI (> 32 mL/m2). Both groups were compared regarding clinical and echocardiographic characteristics, in- and out-of-hospital outcomes, and occurrence of ECM in up to 365 days. Results: Increased LAVI was observed in 78 patients (45%), and was associated with older age, higher body mass index, hypertension, history of myocardial infarction and previous angioplasty, and lower creatinine clearance and ejection fraction. During hospitalization, acute pulmonary edema was more frequent in patients with increased LAVI (14.1% vs. 4.3%, p = 0.024). After discharge, the occurrence of combined outcome for MCE was higher (p = 0.001) in the group with increased LAVI (26%) as compared to the normal LAVI group (7%) [RR (95% CI) = 3.46 (1.54-7.73) vs. 0.80 (0.69-0.92)]. After Cox regression, increased LAVI increased the probability of MCE (HR = 3.08, 95% CI = 1.28-7.40, p = 0.012). Conclusion: Increased LAVI is an important predictor of MCE in a one-year follow-up.

Heat and mass transfer in tubular inorganic membranes

Inorganic membranes, permeation, diffusion, heat transfer, mass transfer, axial dispersion

Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats

Background: In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Objective: Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Methods: Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. Results: No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Conclusion: Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN.

Prevalence of Burnout Syndrome in Patients Admitted with Acute Coronary Syndrome

Background: Burnout Syndrome is the extreme emotional response to chronic occupational stress, manifesting as physical and mental exhaustion. Although associated with higher prevalence of cardiovascular risk factors, no study so far has evaluated whether the Burnout Syndrome could be a prevalent factor in non-elderly individuals active in the labor market, admitted for acute coronary syndrome (ACS). Objective: To evaluate the prevalence of the Burnout Syndrome in non-elderly, economically active patients, hospitalized with ACS. Methods: Cross-sectional study conducted in a tertiary and private cardiology center, with economically active patients aged <65 years, hospitalized with diagnosis of ACS. The Burnout Syndrome was evaluated with the Burnout Syndrome Inventory (BSI), which assesses workplace conditions and four dimensions that characterize the syndrome: emotional exhaustion (EE), emotional distancing (EmD), dehumanization (De) and professional fulfillment (PF). The Lipp’s Stress Symptoms Inventory for Adults (LSSI) was applied to evaluate global stress. Results: Of 830 patients evaluated with suspected ACS, 170 met the study criteria, 90% of which were men, overall average age was 52 years, and 40.5% had an average income above 11 minimum wages. The prevalence of the Burnout Syndrome was 4.1%. When we evaluated each dimension individually, we found high EE in 34.7%, high De in 52.4%, high EDi in 30.6%, and low PF in 5.9%. The overall prevalence of stress was 87.5%. Conclusion: We found a low prevalence of Burnout Syndrome in an economically active, non-elderly population among patients admitted for ACS in a tertiary and private hospital.

Serum Potassium Levels Inversely Correlate with D-Dimer In Patients with Acute-Onset Atrial Fibrillation

Background: D-dimer values are frequently increased in patients with atrial fibrillation (AF) compared to subjects in sinus rhythm. Hypokalemia plays a role in several cardiovascular diseases, but little is known about the association with AF. Objective: D-dimer values are frequently increased in patients with atrial fibrillation (AF) compared with subjects in sinus rhythm. Hypokalemia plays a role in several cardiovascular diseases, but little is known about the association with AF. The aim of this study was to investigate correlations between D-dimer and serum potassium in acute-onset AF (AAF). Methods: To investigate the potential correlation between the values of serum potassium and D-dimer in patients with AAF, we retrospectively reviewed clinical and laboratory data of all emergency department visits for AAF in 2013. Results: Among 271 consecutive AAF patients with D-dimer assessments, those with hypokalemia (n = 98) had significantly higher D-dimer values than normokalemic patients (139 versus 114 ng/mL, p = 0.004). The rate of patients with D-dimer values exceeding the diagnostic cut-off was higher in the group of patients with hypokalemia than in those with normal serum potassium (26.5% versus 16.2%; p = 0.029). An inverse and highly significant correlation was found between serum potassium and D-dimer (r = −0.21; p < 0.001), even after adjustments for age and sex (beta coefficient −94.8; p = 0.001). The relative risk for a positive D-dimer value attributed to hypokalemia was 1.64 (95% CI, 1.02 to 2.63; p = 0.040). The correlation remained statistically significant in patients free from antihypertensive drugs (r = −0.25; p = 0.018), but not in those taking angiotensin-receptor blockers, angiotensin-converting enzyme inhibitors, or diuretics. Conclusions: The inverse correlation between values of potassium and D-dimer in patients with AAF provides important and complementary information about the thromboembolic risk of these patients.

Influence of Spironolactone on Matrix Metalloproteinase-2 in Acute Decompensated Heart Failure

Background: Matrix metalloproteinases (MMPs) are a family of enzymes important for the resorption of extracellular matrices, control of vascular remodeling and repair. Increased activity of MMP2 has been demonstrated in heart failure, and in acutely decompensated heart failure (ADHF) a decrease in circulating MMPs has been demonstrated along with successful treatment. Objective: Our aim was to test the influence of spironolactone in MMP2 levels. Methods: Secondary analysis of a prospective, interventional study including 100 patients with ADHF. Fifty patients were non-randomly assigned to spironolactone (100 mg/day) plus standard ADHF therapy (spironolactone group) or standard ADHF therapy alone (control group). Results: Spironolactone group patients were younger and had lower creatinine and urea levels (all p < 0.05). Baseline MMP2, NT-pro BNP and weight did not differ between spironolactone and control groups. A trend towards a more pronounced decrease in MMP2 from baseline to day 3 was observed in the spironolactone group (-21 [-50 to 19] vs 1.5 [-26 to 38] ng/mL, p = 0.06). NT-pro BNP and weight also had a greater decrease in the spironolactone group. The proportion of patients with a decrease in MMP2 levels from baseline to day 3 was also likely to be greater in the spironolactone group (50% vs 66.7%), but without statistical significance. Correlations between MMP2, NT-pro BNP and weight variation were not statistically significant. Conclusion: MMP2 levels are increased in ADHF. Patients treated with spironolactone may have a greater reduction in MMP2 levels.