Expression of Heparan Sulphate N-deacetylase/N-sulphotransferase by Vascular Smooth Muscle Cells

Heparan sulphate is an important mediator in determining vascular smooth muscle cell (SMC) phenotype. The sulphation pattern of the heparan sulphate chains is critical to their function. We have examined the initial step in the biosynthesis of the sulphated domains mediated by the enzyme heparan sulphate N-deacetylase/N-sulphotransferase (NDST). Rabbit aortic SMC in primary culture exhibited NDST enzyme activity and expressed NDST-1 in their Golgi apparatus, with maximal expression in SMC 2 days after dispersal in primary culture confirmed by Western blot analysis. Endothelial cells, macrophages and fibroblasts expressed NDST-1 but had generally less intense staining than SMC, although SMC expression decreased with culture. The uninjured rat aorta also showed widespread expression of NDST-1. After balloon de-endothelialisation, NDST-1 could not be detected in SMC of the neointima in the early stages of neointimal formation, but was re-expressed at later time points (after 12 weeks). In human coronary arteries, SMC of the media and the diffuse intimal thickening expressed NDST-1, while SMC in the atherosclerotic plaque were negative for NDST-1. We conclude that SMC may regulate their heparan sulphate sulphation at the level of expression of the enzyme heparan sulphate NDST in a manner related to their phenotypic state.

Will chymase inhibitors be the next major development for the treatment of cardiovascular disorders?

Chymase is contained in the secretory granules of mast cells. In addition to the synthesis of angiotensin II, chymase is involved in transforming growth factor-beta activation and cleaves Type I procollagen to produce collagen. NK301 and BCEAB are orally-active inhibitors of chymase. NK301 was tested in a dog model of vascular intimal hyperplasia after balloon injury and shown to reduce the increased chymase activity in the injured arteries and prevent intimal thickening. In a hamster model of cardiac fibrosis associated with cardiomyopathy, BCEAB reduced the increased cardiac chymase activity in cardiomyopathy and reduced fibrosis. Chymase inhibitors may be an important development for the treatment of cardiovascular injury associated with mast cell degranulation.

The Lake Tekapo experiment (LTEX): An investigation of atmospheric boundary layer processes in complex terrain

A research program on atmospheric boundary layer processes and local wind regimes in complex terrain was conducted in the vicinity of Lake Tekapo in the southern Alps of New Zealand, during two 1-month field campaigns in 1997 and 1999. The effects of the interaction of thermal and dynamic forcing were of specific interest, with a particular focus on the interaction of thermal forcing of differing scales. The rationale and objectives of the field and modeling program are described, along with the methodology used to achieve them. Specific research aims include improved knowledge of the role of surface forcing associated with varying energy balances across heterogeneous terrain, thermal influences on boundary layer and local wind development, and dynamic influences of the terrain through channeling effects. Data were collected using a network of surface meteorological and energy balance stations, radiosonde and pilot balloon soundings, tethered balloon and kite-based systems, sodar, and an instrumented light aircraft. These data are being used to investigate the energetics of surface heat fluxes, the effects of localized heating/cooling and advective processes on atmospheric boundary layer development, and dynamic channeling. A complementary program of numerical modeling includes application of the Regional Atmospheric Modeling System (RAMS) to case studies characterizing typical boundary layer structures and airflow patterns observed around Lake Tekapo. Some initial results derived from the special observation periods are used to illustrate progress made to date. In spite of the difficulties involved in obtaining good data and undertaking modeling experiments in such complex terrain, initial results show that surface thermal heterogeneity has a significant influence on local atmospheric structure and wind fields in the vicinity of the lake. This influence occurs particularly in the morning. However, dynamic channeling effects and the larger-scale thermal effect of the mountain region frequently override these more local features later in the day.

Avaliação do perfil hemodinâmico de válvulas aórticas percutâneas: análise comparativa entre os dois dispositivos disponíveis no mercado - válvula auto-expansível e válvula expansível por balão

Mestrado em Tecnologia de Diagnóstico e Intervenção Cardiovascular. Área de especialização: Intervenção Cardiovascular.

Intervenção coronária percutânea no enfarte agudo do miocárdio: influência no prognóstico dos doentes

Mestrado em Tecnologia de Diagnóstico e Intervenção Cardiovascular. Área de especialização: Intervenção Cardiovascular.

Adesão à terapêutica como determinante da efectividade dos cuidados de saúde: a problemática da não adesão à terapêutica em doentes submetidos a angioplastia transluminal percutânea coronária

Mestrado em Intervenção Sócio-Organizacional na Saúde - Área de especialização: Políticas de Administração e Gestão de Serviços de Saúde.

The Prognostic Impact of Renal Failure in Patients with ST-Segment Elevation Acute Myocardial Infarction

INTRODUCTION: Renal insufficiency (RI) is associated with higher morbidity and mortality in patients (P) with coronary artery disease and in P submitted to angioplasty. In ST-segment elevation acute myocardial infarction (STEAMI), this impact has not been well demonstrated. AIM: To evaluate the impact of RI in P with STEAMI. METHODS: We evaluated 160 P admitted with STEAMI, mean age of 62+/-14 years, 76% male. We determined creatinine levels on admission. RI was defined as a level >1.5 mg/dl. Analysis of clinical, electrocardiographic and laboratory variables was performed, in relation to the endpoint defined as the occurrence of death at 30-day follow-up. RESULTS: There were 16 deaths (10%) at 30-day follow-up. P with RI (n=21) were older (68+/-11 vs 61+/-14 years, p<0.001), more often had diabetes (57 vs 24 %, p=0.004) and presented more often with Killip class > or =2 (57 vs 12%, p<0.001). The use of statins (62 vs 83%, p=0.05) and beta-blockers (24 vs 65%, p<0.001) was lower in P with RI. Mortality was higher in RI P (62 vs 2%, p<0.001). The univariate predictors of death were age > or =75 years, diabetes, Killip class > or =2 on admission, RI, non-use of statins and beta-blockers and use of diuretics. In multivariate analysis, independent predictors of death at 30 days were RI (HR 29.6, 95% CI 6.3-139.9, p<0.001) and non-use of beta-blockers (HR 0.13, 95% CI 0.02-1.01, p=0.01). CONCLUSION: In P admitted for STEAMI, the presence of RI was an independent predictor of death at 30 days whereas the usage of beta-blockers was protective.

Importância da Presença de Lesões Adicionais Complexas no Contexto de Angioplastia Primária no Enfarte Agudo do Miocárdio no Prognóstico a Médio-Prazo

Introdução: Existe alguma controvérsia respeitante ao tipo de revascularização a efectuar no contexto de angioplastia (PCI) primária no enfarte agudo do miocárdio (EAM). A presença de lesões coronárias adicionais, particularmente complexas, poderá ter impacto no prognóstico. Objectivos: Avaliar o prognóstico a médio-prazo (1 ano) face à presença de lesões adicionais complexas após PCI primária. População e Métodos: Estudaram-se retrospectivamente 138 doentes consecutivos admitidos na nossa Unidade por EAM com elevação do segmento ST e submetidos a PCI primária. Os doentes foram seguidos por um período de 1 ano e divididos em 2 grupos: sem lesões adicionais complexas (n=69, 61 ± 14 anos, 62% sexo masculino) e com lesões adicionais complexas (n=69, 65 ± 13 anos, 73% sexo masculino, p=NS). Avaliaram-se as características demográficas, factores de risco para doença coronária, história prévia cardíaca, e presença de sinais de insuficiência cardíaca na admissão. Foram também avaliadas características angiográficas, medicação efectuada e resultado da PCI. Avaliou-se o impacto das variáveis na ocorrência combinada de morte/re-enfarte/revascularização miocárdica ao primeiro ano. Resultados: A taxa de sucesso angiográfico foi de 96,4%. O grupo com idade igual ou superior a 75 anos representa 24% da população e 4,3% apresentaram-se em classe Killip IV. A localização anterior foi ligeiramente superior no grupo sem lesões adicionais complexas (60% vs. 44%, p=0,06), a inferior no grupo com lesões adicionais complexas (26% vs. 42%, p=0,07). A doença de 1 vaso foi mais prevalente no grupo sem lesões adicionais complexas como esperado (86% vs. 11%, p<0,001). A utilização de stent foi mais frequente no grupo sem lesões adicionais complexas (96% vs. 86%, p=0,08). Não houve diferenças nas restantes variáveis. A taxa de morte/re-enfarte/revascularização foi superior no grupo com lesões adicionais complexas (13% vs. 32%, p=0,014). Até aos 13 dias de seguimento, ocorreram 67% dos eventos. Na análise univariada, os factores predizentes de eventos foram a classe Killip 2, fluxo TIMI < 3 no vaso relacionado com enfarte após PCI, a não utilização de antagonistas da glicoproteína IIb/IIIa, bloqueadores beta e estatinas, doença multivaso e presença de lesões adicionais complexas (Log-rank, p=0,003). Na análise multivariável, os factores predizentes independentes de prognóstico a 1 ano foram a classe Killip 2 (Odds ratio 0,28%; IC 95% 0,08-0,93, p=0,037) e a presença de lesões adicionais complexas (OR 0,32; IC 95% 0,12-0,84, p=0,020). Conclusões: A presença de lesões adicionais complexas após PCI primária tem um pior prognóstico ao primeiro ano, sugerindo a necessidade de intervenção para a sua estabilização, particularmente nos primeiros 30 dias após enfarte.

Angioplastia Directa como Terapêutica de Reperfusão no Idoso Acima dos 75 Anos

Introdução: A angioplastia primária é a terapêutica de reperfusão com melhores resultados no enfarte agudo do miocárdio (EAM). Este facto assume particular relevância na população acima dos 75 anos, em que o risco hemorrágico relacionado com a trombólise se associa ao acréscimo de mortalidade condicionado pela idade. Objectivos: Avaliar em doentes com síndrome coronário agudo (SCA) com supradesnivelamento do segmento ST e submetidos a angioplastia directa, a influência da idade nos resultados, incluindo evolução clínica, morbilidade e mortalidade intrahospitalar. População e métodos: Análise retrospectiva de 245 doentes consecutivos admitidos entre Janeiro de 2000 e Dezembro de 2001 por SCA com supradesnivelamento ST, com idades entre os 31 e 90 anos (63+-13), submetidos a angioplastia primária. Destes, 46 doentes (18,8%) com idade superior a 75 anos foram comparados com os restantes. Avaliaram-se os seguintes parâmetros: factores de risco cardiovascular – hipertensão arterial (HTA), diabetes mellitus (DM), tabagismo, dislipidémia, história familiar -, antecedentes de angina ou EAM e angioplastia prévia; extensão de doença coronária, resultados, evolução clínica e mortalidade intrahospitalar. Resultados: Nos doentes com idade superior a 75 anos, o sexo feminino foi predominante (26 doentes, 56,5%), assim como a existência de HTA, angina e DM tipo2, embora sem significado estatístico. O tabagismo foi mais prevalente em idades inferiores (54,3% vs 13%;p<0,001), assim como EAM antigo (p<0,05). A taxa de sucesso primário global foi de 96,7% (93,5% no grupo acima de 75 anos). A doença de 3 vasos foi significativamente mais frequente na população idosa (41,3% vs 26,2%; p<0,05); a utilização de inibidores da glicoproteína IIb/IIIa foi menor (80,4% vs 91%;p<0,05). A evolução em classe clínica Killip (KK) foi mais favorável no grupo com menos de 75 anos (KKI: 88,4% vs 69,8%;p<0,001). Dos eventos estudados, observámos na população idosa maior ocorrência de complicações hemorrágicas minor (3,5% vs 13,0%; p<0,05) e de morte intrahospitalar (4,5% vs 19,6%; p<0,001). Conclusão: A angioplastia primária mantém nesta população uma taxa de sucesso primário semelhante. A maior incidência de complicações hemorrágicas implica um maior cuidado na selecção da terapêutica antitrombótica adjuvante. A mortalidade significativamente mais alta neste grupo etário mantém-se, mesmo quando a angioplastia é o método de reperfusão escolhido.

O Valor Prognóstico da Resposta Neutrofílica na Era da Reperfusão Mecânica do Enfarte Agudo do Miocárdico

BACKGROUND: In ST-segment elevation myocardial infarction (STEMI) patients treated with primary angioplasty, neutrophil response and its prognostic significance are not entirely understood. METHODS: We retrospectively studied 305 consecutive and non-selected STEMI patients. They were divided into three groups according to the maximum neutrophil percentage in the first 48 hours. We compared baseline demographic characteristics, coronary disease risk factors, cardiac history, clinical presentation, therapeutics administered and clinical evolution. We then assessed survival in the three groups and determined predictors of 30-day mortality. Group 1 (G1) had a mean age of 57 +/- 14 years and showed mean neutrophilia of 73.3%, Group 2 (G2) 61 +/- 13 years and 79.9%, and Group 3 (G3) 66 +/- 13 years and 84.2%. We compared outcomes and 30-day mortality between the groups. RESULTS: Mean age rose with increased neutrophil response. There were no statistically significant baseline differences between the groups except for more smokers in Groups 1 and 2, and more patients presenting with Killip class > or = 2 and fewer with uncomplicated evolution in Group 3. During 30-day follow-up there were 19 deaths (G1=1, G2=3 and G3=15). In univariate analysis mortality predictors were age > or = 75 years, anterior STEMI, maximum creatinine kinase > or = 2500 UI/L, culprit lesion in proximal anterior descending artery, incomplete revascularization, Killip > or = 2 at presentation, and being in G3. After multivariate regression analysis independent predictors were age > or = 75 years, incomplete revascularization and being in G3. CONCLUSION: In myocardial infarction patients undergoing mechanical revascularization, an intense neutrophil response (routinely, easily and inexpensively assessed) is related to worse short-term prognosis.

Impacto da Obesidade nos Resultados após Angioplastia Primária em Doentes com Enfarte Agudo do Miocárdio com Elevação do Segmento ST

INTRODUCTION: Obesity is an important risk factor for the development of diabetes, hypertension, coronary disease, left ventricular dysfunction, stroke and cardiac arrhythmias. Paradoxically, previous studies in patients undergoing elective coronary angioplasty showed a reduction in hospital and long-term mortality in obese patients. The relation with body mass index (BMI) has been less studied in the context of primary angioplasty. OBJECTIVES: To evaluate the impact of obesity on the results of ST-segment elevation acute myocardial infarction treated by primary angioplasty. METHODS: This was a study of 464 consecutive patients with ST-segment elevation acute myocardial infarction undergoing primary angioplasty, 78% male, mean age 61 +/- 13 years. We assessed in-hospital, 30-day and one-year mortality according to BMI. Patients were divided into three groups according to BMI: normal--18-24.9 kg/m2 (n = 171); overweight--25-29.9 kg/m2 (n = 204); and obese-- > 30 kg/m2 (n = 89). RESULTS: Obese patients were younger (ANOVA, p < 0.001) and more frequently male (p = 0.014), with more hypertension (p = 0.001) and dyslipidemia (p = 0.006). There were no differences in the prevalence of diabetes, previous cardiac history, heart failure on admission, anterior location, multivessel disease, peak total CK or medication prescribed, except that obese patients received more beta-blockers (p = 0.049). In-hospital mortality was 9.9% for patients with normal BMI, 3.4% for overweight patients and 6.7% for obese patients (p = 0.038). Mortality at 30 days was 11 4.4% and 7.8% (p = 0.032) and at one year 12.9%, 4.9% and 9% (p = 0.023), respectively. On univariate analysis, overweight was the only BMI category with a protective effect; however, after multivariate logistic regression analysis, adjusted for confounding variables, none of the BMI categories could independently predict outcome. CONCLUSIONS: Overweight patients had a better prognosis after primary angioplasty for ST-segment elevation acute myocardial infarction compared with other BMI categories, but this was dependent on other potentially confounding variables.

Serial Changes in Oxidized Low-Density Lipoprotein Associated with Culprit Vessel in ST - Elevation Myocardial Infarction - a Promising Marker?

The aim of the present study was to investigate variations in oxidized LDL (oxLDL) at the onset of acute myocardial infarction (AMI) and over the recovery period, exploring their relationship with coronary disease severity. A follow-up of 50 AMI patients was evaluated against 25 healthy volunteers (reference group). The AMI patients were evaluated at three time points: at admission before the administration of IIb/IIIa inhibitors and angioplasty, and two and 40 days after intervention. Plasma oxLDL concentrations were measured by ELISA. oxLDL was found to be significantly higher in AMI patients in the acute phase relative to reference levels, decreasing progressively over the recovery period. The results also demonstrated that oxLDL levels were decreased in patients with the left circumflex artery (LCX) as culprit vessel compared to the left anterior descending coronary (LAD) or right coronary artery (RCA). The results highlight a significant increase in oxLDL concentration related to coronary artery disease severity, as conditions such as LCX lesions are usually associated with a favorable prognosis, contrasting with LAD-associated conditions that can compromise large areas of myocardium. The results thus suggest that oxLDL may constitute a promising marker in assessment of AMI evolution.

Utilização de Stents Revestidos com Fármaco em Angioplastia Primária - Resultados Clínicos a Longo Prazo

INTRODUCTION: The use of drug-eluting stents in the context of mechanical reperfusion following ST-segment elevation myocardial infarction (MI) was initially viewed with concern. The main fear was that the drugs' action in unstable lesions could increase the risk of thrombotic stent occlusion. Furthermore, there was no evidence that the proven benefit of reduced instent restenosis could be extended to such patients, since they were excluded from the initial clinical trials. OBJECTIVES: To assess the safety and long-term clinical outcomes of the use of drug-eluting stents in primary angioplasty. METHODS: The first 100 consecutive and non-selected patients admitted for MI and treated by primary angioplasty with drug-eluting stent implantation in the target lesion were analyzed retrospectively. The efficacy and safety of the procedure, in-hospital clinical evolution and the occurrence of major adverse cardiac events in the first year were assessed. RESULTS: Patients' mean age was 58.2 +/- 11.5 years, and 78 were male. The success rate of primary angioplasty was 99%. Stents coated with sirolimus were used in 67 patients, paclitaxel in 19 and dexamethasone in 16. In-hospital mortality was 3%. The follow-up rate at 12 months was 98%. During this period, the rate of target vessel revascularization was 1% (with no patient requiring target lesion revascularization), MI 2%, and overall mortality 3.9%. Fourteen patients had clinical indication for repeat coronary angiography, which showed no significant in-stent restenosis. One event was considered to be due to acute stent thrombosis. The incidence of major adverse events was 5.9%. CONCLUSION: The use of drug-eluting stents in MI patients undergoing primary mechanical revascularization is safe and is associated with a reduced incidence of major adverse events, thrombosis and clinical restenosis at one year.

Trombose Muito Tardia de Stent Coronário Após Suspensão de Terapêutica Antiagregante Plaquetária

Percutaneous transluminal coronary angioplasty (PTCA) with stent placement is widely used to achieve myocardial revascularization in patients with symptomatic ischemic heart disease and significant coronary artery stenosis. Drug-eluting stents are used in most patients undergoing percutaneous angioplasty. Stent thrombosis is an uncommon but serious complication, manifested mostly by sudden death or acute ST-elevation myocardial infarction. The authors report the case of a 68-year-old patient with acute anterior ST-elevation myocardial infarction. Five years previously, she had had a similar presentation and underwent primary angioplasty of the left anterior descending artery with implantation of a drug-eluting stent. The patient was discharged under antithrombotic therapy. She discontinued antiplatelet therapy and two days later suffered an acute anterior myocardial infarction. Primary angioplasty revealed stent thrombosis.

Existem Diferenças nos Resultados da Angioplastia Directa no Sexo Feminino?

Introdução: Em doentes com enfarte agudo do miocárdio (EAM), a angioplastia percutânea (ACTP) é de forma crescente aceite como a terapêutica de reperfusão mais eficaz. No sexo feminino estão descritos factores com implicação prognóstica na evolução do EAM. Existem diferenças detectáveis de morbilidade e mortalidade, após ACTP directa, no sexo feminino? Objectivos: Avaliar o perfil clínico e os resultados, em termos de morbilidade e mortalidade intrahospitalar, em mulheres submetidas a angioplastia directa por síndrome coronário agudo (SCA) com supradesnivelamento do segmento ST. Metodologia: Análise retrospectiva de 245 doentes consecutivos, 72 dos quais do sexo feminino (29,4 %), admitidos entre Janeiro de 2000 a Dezembro de 2001 por SCA com supradesnivelamento do segmento ST e submetidos a ACTP directa. Avaliámos a prevalência dos vários factores de risco cardiovascular – hipertensão arterial (HTA), tabagismo, dislipidémia, diabetes mellitus, história familiar –; antecedentes pessoais de angina, EAM e angioplastia prévios; horas de evolução do enfarte; características angiográficas e evolução clínica.Resultados: Do estudo descritivo dos dados, verificou-se que os doentes do sexo feminino eram mais idosos (67,9 ± 11,6 vs 59,6 ± 13; p < 0,001), com maior prevalência de HTA (65,3% vs 47,4 %; p < 0,05) e angina (29,0% vs 16,0 %; p < 0,05) e menor prevalência de tabagismo (27,8% vs 54,3 %; p < 0,001). A demora média (horas) entre o início da sintomatologia e a ACTP foi significativamente maior nas mulheres (6,8 ± 4,1 vs 5,4 ± 3,7; p < 0,05). Angiograficamente, o número de lesões existentes e abordadas foi semelhante nos dois grupos. Utilizaram-se inibidores da glicoproteína IIb/IIIa em 84,7% das mulheres e 90,8% dos homens. Dos eventos considerados, verificou-se maior ocorrência de complicações hemorrágicas minor (5,6% vs 5,2 %), arritmias (15,3% vs 10,4 %) e mortalidade intrahospitalar (9,7% vs 6,4 %) no sexo feminino, sem no entanto apresentar significado estatístico. A demora média intra- -hospitalar foi semelhante nos dois grupos. Conclusão: Apesar da crescente preocupação com a homogeneidade de abordagens diagnósticas e terapêuticas nos dois sexos, particularmente no acesso a terapêutica de reperfusão, a morbilidade e mortalidade são tendencialmente superiores na nossa população, sem contudo atingir significado estatístico. A idade mais avançada e a maior demora até à realização da angioplastia, podem explicar esta discrepância.