Local delivery of sirolimus nanoparticles for the treatment of in-stent restenosis.

OBJECTIVES: To test the local delivery of sirolimus nanoparticles following percutaneous transluminal coronary angioplasty (PTCA) to treat in-stent restenosis (ISR) in a swine model. BACKGROUND: Coronary bare-metal stent (BMS) implantation reduces major adverse cardiac events when compared with PTCA; however, ISR rates remain high. METHODS: Eighteen swine underwent BMS deployment guided by intravascular ultrasound (IVUS). Of these, 16 developed ISR (1 stent/swine) and underwent angioplasty with a noncompliant balloon (PTCA-NC). The animals were then randomized into four groups for local infusion of sirolimus nanoparticles through a porous balloon catheter, as follows: (1) PTCA-NC alone (control); (2) PTCA-NC + (polylactic acid)-based nanoparticle formulation (anionic 1); (3) PTCA-NC + (polylactic-co-glycolic acid)-based nanoparticle formulation (anionic 2); and (4) PTCA-NC + Eudragit RS nanoparticle formulation (cationic). Coronary angiography and IVUS follow-up were performed 28 days after ISR treatment. RESULTS: There was one episode of acute coronary occlusion with the cationic formulation. Late area loss was similar in all groups at 28 days according to IVUS. However, luminal volume loss (control = 20.7%, anionic 1 = 4.0%, anionic 2 = 6.7%, cationic = 9.6%; P = 0.01) and neointimal volume gain (control = 68.7%, anionic 1 = 17.4%, anionic 2 = 29.5%, cationic = 31.2%; P = 0.019) were significantly reduced in all treatment groups, especially in anionic 1. CONCLUSIONS: PTCA-NC followed by local infusion of sirolimus nanoparticles was safe and efficacious to reduce neointima in this model, and this strategy may be a promising treatment for BMS ISR. Further studies are required to validate this method in humans.

Identificação de genes envolvidos na síntese de proteínas de células musculares lisas com expressão aumentada em placas ateromatosas associados a hiperplasia neointimal após implante de stents não-farmacológicos: estudo GENESIS-R / Identification of genes involved in smooth muscle cell protein synthesis with increased expression in atheromathous plaques associated to neointim al hyperplasia after bare-metal stenting: GENESISI-R Study

Introdução: A reestenose coronária é um fenômeno pouco compreendidoe que permanece como um desafio mesmo na era dos stents farmacológicos. Este estudo tem como objetivo identificar genes envolvidos na síntese de proteínas estruturais e funcionais de células musculares lisas com expressão aumentada em placas ateromatosas de humanos associadosa hiperplasia neointimal após o implante de stents não-farmacológicos. Métodos: Placas ateromatosas foram obtidasmediante aterectomia direcionada, previamente ao implante do stent. A análise da expressão dos genes foi realizada utilizando-se o sistema Affymetrix GeneChip. Os pacientes foramsubmetidos a ultrassom intracoronário 6 meses após o procedimento para análise volumétrica intrastent. Foi avaliada a correlação entre a expressão gênica de placas ateromatosas e o porcentual de hiperplasia intimal intrastent. Resultados: A maioria dos pacientes era do sexo masculino (85,7%), com60,2 ± 11,4 anos de idade, 35,7% eram diabéticos e o porcentual de hiperplasia intimal intrastent foi de 29,9 ± 18,7%.Não houve variação do porcentual de hiperplasia intimal intrastent entre os pacientes com ou sem diabetes (29,5% vs. 30,7%; P = 0,89). Não houve correlação entre a extensão do stent e o porcentual de hiperplasia intimal intrastent (r = -0,26; P = 0,26) ou entre o diâmetro do stent e o porcentual dehiperplasia intimal intrastent (r = 0,14; P = 0,56). Oito genes envolvidos na síntese de proteínas estruturais e funcionais de células musculares lisas apresentaram correlação positiva como porcentual de hiperplasia intimal intrastent. Conclusões: As lesões coronárias de novo apresentam expressão aumentada de genes relacionados com a síntese de proteínas estruturais e funcionais de células musculares lisas associados a futurahiperplasia neointimal intrastent significativa, surgindo como novos alvos terapêuticos.

First-in-man study of simvastatin-eluting stent in de novo coronary lesions: the SIMVASTENT study.

BACKGROUND: Statins have anti-inflammatory and antiproliferative properties irrespective of their cholesterol-lowering effects. The aim of the present study was to evaluate a simvastatin-eluting stent (SimvES) in the treatment of de novo coronary lesions. METHODS AND RESULTS: Forty-two patients with de novo coronary artery lesions were assigned to SimvES, bare-metal stent (BMS) or everolimus-eluting stent (EES) implantation followed by intravascular ultrasound (IVUS) for neointimal quantitative analysis. Six months later, quantitative coronary angiography (QCA) and IVUS were repeated. QCA showed no binary restenosis, a mean in-stent late loss of 1.05 ± 0.25 mm (BMS, 1.12 ± 0.48 mm; EES, 0.20 ± 0.16 mm) and a diameter stenosis of 33.5 ± 7.1% (BMS, 35.5 ± 15.30%; EES, 7.2 ± 3.12%). Control IVUS showed a mean in-stent obstruction of 18.3 ± 9.4% (BMS, 32.8 ± 19.1%; EES, 9.8 ± 2.4%) and a neointimal volume index of 1.58 ± 0.75 mm(3)/mm (BMS, 2.93 ± 1.76 mm(3)/mm; EES, 0.80 ± 0.16 mm(3)/mm). Thrombus, late incomplete apposition and major adverse cardiac events were not observed. CONCLUSIONS: In this sample of patients with de novo coronary lesions, the use of a SimvES was not related to major adverse cardiac events, but it was associated with a higher level of neointimal proliferation than expected.

Endovascular repair of ascending aorta and coronary stent implantation.

Endovascular treatment of ascending aorta pseudoaneurysms with coronary stents implantation at the same procedure was feasible, although longer followup is necessary.

Racional e desenho do registro brasileiro de implante de bioprótese aórtica por cateter / Rationale and design of the Brazilian transcatheter aortic valve implantation registry

Introdução: A substituição cirúrgica da valva aórtica é o tratamento de eleição para pacientes com estenose aórtica acentuada. Entretanto, o risco cirúrgico aumenta expressivamente com o avançar da idade e com a associação de comorbidades. Recentemente, iniciou-se a experiência com o implante por cateter de biopróteses aórticas no Brasil. Justifica-se, portanto, a criação de um registro nacional para conhecimento dos resultados desse tipo de procedimento em nosso meio. Descrevemos o racional e o desenho do Registro Brasileiro de Implante de Bioprótese Aórtica por Cateter. Métodos: Trata-se de um registro multicêntrico, prospectivo, que incluirá 200 pacientes portadores de estenose valvar aórtica sintomática de alto risco cirúrgico submetidos a implante por cateter de bioprótese valvular aórtica em centros brasileiros. O desfecho primário do estudo é a mortalidade por qualquer causa aos 30 dias, 12 meses e 24 meses. Os desfechos secundários avaliados incluem, entre outros: 1) sucesso técnico do implante da bioprótese;2) mortalidade cardiovascular aos 30 dias, 12 meses e 24 meses; 3) desfecho combinado de segurança aos 30 dias; e 4) desfecho combinado de eficácia aos 12 meses e 24 meses. Conclusões: A análise dos resultados desse registro nacional permitirá avaliar os defechos do implante percutâneo de biopróteses aórticas em nosso meio.

Background: Surgical replacement of the aortic valve is the therapy of choice for patients with severe aortic stenosis.However, the surgical risk increases dramatically as age advances and with the association of comorbidities. Recently, transcatheter aortic valve implantation has been introduced in Brazil. Therefore, it was important to create a national registry to determine the outcomes of this procedure in our country. The rationale and design of the Brazilian Transcatheter Aortic Valve Implantation Registry is described.Methods: This is a multicenter prospective registry, including 200 patients with symptomatic aortic valve stenosis and high surgical risk submitted to transcatheter aortic valve implantation in Brazilian institutions. The primary endpoint of the study is all cause mortality at 30 days, 12 and 24 months. Secondary endpoints, among others, are: 1) technical success of transcatheter valve implantation; 2)cardiovascular mortality at 30 days, 12 and 24 months; 3) composite safety endpoint at 30 days; and 4) compositeefficacy endpoint at 12 and 24 months. Conclusions: The analysis of the results of this national registry will enable us to evaluate the outcomes of transcatheter aortic valve implantation in our country.

Endovascular approach to treat ascending aortic pseudoaneurysm in a patient with previous CABG and very high surgical risk.

Pseudoaneurysm of the ascending aorta is an uncommon pathology and a challenge in high-risk patients who undergo conventional surgery because of high operative morbidity and mortality. Endovascular exclusion of an aortic pseudoaneurysm using an endoprosthesis is a less invasive approach, but few such cases have been reported. Moreover, the use of this approach poses unique therapeutic challenges because there is no specific endoprosthesis for ascending aortic repair, particularly to treat patients with previous coronary artery bypass graft (CABG). We describe the case of a 74-year-old patient who had undergone CABG and later presented with an iatrogenic ascending aortic pseudoaneurysm that occurred during an angiography. This patient was at very high risk for surgical treatment and, therefore, an endovascular approach was adopted: percutaneous coronary intervention for the left main coronary artery, left anterior descending and left circumflex native coronary arteries followed by endovascular endoprosthesis deployment in the ascending aorta to exclude the pseudoaneurysm. Both procedures were successfully performed, and the patient was discharged without complications 4 days later. At 5 months' clinical follow-up, his clinical condition was good and he had no complications.

Erectile dysfunction and coronary artery disease: an association of higher risk in younger men.

INTRODUCTION: The association between erectile dysfunction (ED) and coronary artery disease (CAD) has been described in various settings, but it is unclear if there is an independent interaction with age. AIM: To investigate the interaction of age in the association between ED and CAD. METHODS: This case-control study was conducted among 242 patients referred for elective coronary angiography. One hundred fourteen patients with significant CAD were identified as cases and 128 controls without significant CAD. ED was evaluated by the erectile function domain of the International Index of Erectile Function (IIEF) questionnaire, determined by a score ≤ 25 points. MAIN OUTCOME MEASURES: Significant CAD was based on stenosis of 50% or greater in the diameter in at least one of the major epicardial vessels or their branches. The analysis was conducted in the whole sample and according to the age strata, controlling for the effects of cardiovascular risk factors, testosterone, and C-reactive protein. Results. Patients had on average 58.3 ± 8.9 years. CAD and ED were associated exclusively in patients younger than 60 years (ED in 68.8% of patients with CAD vs. 46.7% of patients without CAD, P = 0.009). The association was independent of cardiovascular risk factors, testosterone and C-reactive protein (risk ratio 2.3, 95% confidence interval from 1.04 to 5.19). Severity of CAD was higher in patients younger than 60 years with ED. CONCLUSIONS: Men with less than 60 years of age who report ED presented a higher risk of having chronic CAD and more severe disease diagnosed by coronary angiography.

Modelo experimental de reestenose intrastent em artérias coronárias de suínos: efeito do implante de stent sobredimensionado / Experimental model of in-stent restenosis in swine coronary arteries: effect of oversized stent deployment

INTRODUÇÃO: Há múltiplos modelos experimentais em animais, entretanto o modelo suíno é o que apresenta características anatômicas e funcionais mais próximas às humanas. Assim sendo, esse trabalho foi realizado com o objetivo de desenvolverr e implementar um protocolo experimental de indução de hiperproliferação neointimal em suínos, visando à criação de técnicasw de lesão vascular simulando a reestenose. Método: De agosto de 2006 a março de 2009, 69 suínos jovens da raça Large White foram submetidos a cinecoronariografia seguida de lesão vascular com implante de 102 stents sobredimensionados, guiados por ultrassom intracoronário. Em 28 dias foi realizado reestudo com nova cinecoronariografia e ultrassom intracoronário. Resultados: O diâmetro luminal mínimo e a área luminal mínima imediatamente após o implante de stent no grupo stent sobredimensionado foram maiores em comparação ao grupo controle...

BACKGROUND: There are several experimental animal models, but, the swine model is the most similar to human anatomic and physiologic characteristics. Therefore, this study was carried out to develop and implement an experimental protocol of vascular neointimal hyperplasia induction in swine, aiming at creating vascular injury techniques simulating restenosis. METHOD: From August 2006 to March 2009, 69 young Large White swine underwent coronary angiography followed by vascular injury and implantation of 102 oversized stents guided by intravascular ultrasound. After 28 days a new coronary angiography and intravascular ultrasound was performed. RESULTS: The minimal luminal diameter and the minimal luminal area immediately after the stent deployment in the group treated with an oversized stent were significantly higher when compared to the control group (3.5 ± 0.3 mm vs. 3 ± 0.2 mm, P < 0.0001 and 40.7 ± 0.3 mm² vs. 30.2 ± 0.2 mm², P < 0.0001). The binary restenosis rate in the group treated with an oversized stent was 92% (69/75 stents), whereas it was 12% (3/25 stents) in the control group, with a statistically significant difference (P < 0.0001). The neointimal hyperplasia volume was significantly higher in the group treated with an oversized stent in comparison to the control group (5.9 ± 0.8 mm³/stent mm vs. 1.8 ± 0.7 mm³/stent mm, P < 0.0001). CONCLUSION: The proposed experimental model of neointimal proliferation induction in swine is effective in inducing instent hyperplasia, and therefore it may be used for the study of the pathophysiologic mechanisms of in-stent restenosis as well as for therapeutic purposes, such as the evaluations of new drugs, new devices and new drug-eluting stents for the prevention and treatment of in-stent restenosis.

Thoracic endovascular aortic repair - a Brazilian experience in 255 patients over a period of 112 months.

The aim of this study is to analyze the immediate and late evolution for death and reintervention in a thoracic endovascular aortic repair (TEVAR) group, over a follow-up period of 112 months. Retrospective data of 255 patients, from 1998 to 2007, were obtained. The most prevalent diseases were thoracic aortic aneurysms (89), thoracic and abdominal aneurysms (85) and thoracic aortic dissections (61). The mean age was 63.2 years and 67.1% were male. Three hundred and three endoprostheses were used. Causes of morbidity, in the immediate postoperative period, were hyperthermia (45.9%), endoleaks (9.8% - being 7.1% type I), vascular complications (5.2%), renal insufficiency (3.1%) and neurological complications (3.1%). There were two (0.8%) hospital deaths and 17 (6.7%) late deaths. Time of follow-up was up to 112 months (mean of 60 months). The Kaplan-Meier curve analysis showed an increase of reintervention, compared with death, after a follow-up period of 42 months. Freedom from death at 36, 60 and 112 months was 96%, 89.1%, 85.1% and for reintervention, for the same periods was 93.6%, 82.7%, 57.2%, respectively. This study showed low incidence of prostheses related morbidity and immediate mortality. After a period of 42 months there was an increase on the percentual tax of reintervention.

Endovascular repair of an abdominal aortic aneurysm in patient with horseshoe kidney: a case report.

Horseshoe kidney is a rare congenital anomaly that may cause various technical problems during conventional repairs of abdominal aortic aneurysms. We report the case of a 68-year-old woman with a horseshoe kidney, symptomatic abdominal aortic aneurysm and mild renal failure. The patient underwent endovascular repair using a bifurcated endoprosthesis. The postoperative was uneventful. We describe the diagnosis and the endovascular technique and literature review.

Correção endovascular de aneurisma de aorta abdominal em paciente com rim em ferradura: relato de caso / Endovascular repair of an abdominal aortic aneurysm in patient with horseshoe kidney: a case report

O rim em ferradura é uma anomalia congênita rara que pode causar várias dificuldades técnicas durante a correção convencional de aneurisma de aorta abdominal. Relatamos o caso de uma paciente de 68 anos com rim em ferradura, aneurisma de aorta abdominal sintomático e disfunção renal leve. A paciente foi submetida a correção endovascular, sendo utilizada uma endoprótese bifurcada. O pós-operatório foi livre de complicações. O diagnóstico e a técnica endovascular são discutidos, assim como a literatura revisada.

Horseshoe kidney is a rare congenital anomaly that may cause various technical problems during conventional repairs of abdominal aortic aneurysms. We report the case of a 68-year-old woman with a horseshoe kidney, symptomatic abdominal aortic aneurysm and mild renal failure. The patient underwent endovascular repair using a bifurcated endoprosthesis. The postoperative was uneventful. We describe the diagnosis and the endovascular technique and literature review.

Coronary artery bypass grafting in a patient with situs inversus totalis and dextrocardia.

Situs inversus totalis is a rare congenital anomaly. We report a case of a 78-year-old woman with this condition and ischemic coronary artery disease who underwent myocardial revascularization. The cardiac catheterism showed severe proximal stenosis with aneurysms in the anterior interventricular branch, diagonal artery, and right coronary artery. The procedure was done with the surgeon positioned in the left hand side of the patient, with the right internal thoracic artery anastomosed to the anterior interventricular branch, and to two more vein grafts. Very few cases have been reported in the world and this is the third case in Brazil, and the first in the world with coronary aneurysms.

Revascularização do miocárdio em pacientes com situs inversus totalis e dextrocardia / Coronary artery bypass grafting in a patient with situs inversus totalis and dextrocardia

O situs inversus totalis com dextrocardia é uma situação congênita rara. Relatamos o caso de uma paciente de 78 anos com esta anomalia, em síndrome coronariana aguda. A cinecoronariografia demonstrou lesões proximais graves, com aneurismas em artérias interventricular anterior, diagonal e coronária direita. Foram utilizados a artéria torácica interna direita anastomosada na artéria interventricular anterios e...

Anticoagulação ambulatorial / Outpatient anticoagulation

Por mais de 50 anos, a disponibilidade de anticoagulantes orais tem tornado possível a prevenção primária e secundária efetiva de tromboembolismo arterial e venoso. O maior dilema do uso de anticoagulantes na prática clínica é balançar o benefício da prevenção de eventos tromboembólicos e o risco de complicações hemorrágicas. Apresenta-se neste artigo de revisão um enfoque do uso dos anticoagulantes orais nas seguintes entidades clínicas: tromboembolismo venoso, síndromes coronarianas agudas, fibrilação atrial e próteses valvares cardíacas

For more than 50 years, the availability of oral anticoagulants has promoted effective primary and secondary prevention of arterial and venous thromboembolism. A major dilemma of using anticoagulants in clinical practice is balancing the benefits of preventing thromboembolic events and the risks of hemorrhagic complications. This review article presents an approach to the use of oral anticoagulants in the following diseases: venous thromboembolism, acute coronary syndromes, atrial fibrillation and prosthetic heart valves

Vulnerable plaque detection by temperature heterogeneity measured with a guidewire system: clinical, intravascular ultrasound and histopathologic correlates.

Diagnosing plaque vulnerability may have therapeutic and prognostic implications. We used a heat sensor-tipped thermography guidewire to identify temperature variations in atherosclerotic coronary arteries in patients undergoing stent placement. This study is the first human experience with the ThermoCoil Guidewire (TG). TG consists of a 0.014 inch wire which rotates as it is retracted so as to interrogate the arterial lumen in a helical path. The wire has a temperature sensor in the distal tip with a sensitivity of 0.03 degrees Celcius. In 13 patients presenting with either acute or chronic coronary syndromes as indications for percutaneous coronary intervention, the following parameters were assessed: thermography, intravascular ultrasound (IVUS), angiography and serum markers for inflammation (C-reactive protein) and ischemia (troponin). Directional atherectomy was performed in 2 patients and tissue was analyzed histopathologically. Two patients had unstable angina, 2 had myocardial infarction, and 9 had stable angina as indications for coronary intervention. There were no device-related adverse events or system failures. Thermography was performed on all patients prior to any other intervention. Intra-arterial temperature rises between 0.1 degrees Celcius and 0.3 degrees Celcius were noted in 4 subjects. Intravascular ultrasound findings and atherectomy tissue histology showed correlates of plaque vulnerability in plaques with elevated temperature. In conclusion, thermography using a guidewire-based system can be performed safely, and detected lesions whose IVUS and/or atherectomy findings suggested plaques at high risk for rupture. Further studies will determine the predictive value of thermography or other techniques for assessing plaque composition and risk through noninvasive or invasive means.

Tratamento endovascular dos aneurismas de aorta abdominal: experiência inicial e resultados a curto e médio prazo / Endovascular treatment of abdominal aortic aneurysms: initial experience and short and mid-term results

OBJETIVO: O estudo visa a apresentar os resultados a curto e médio prazo do tratamento endovascular dos aneurismas de aorta abdominal (AAA). Trata-se de uma experiência inicial com uma equipe multidisciplinar. MÉTODO: No período entre julho de 2003 e outubro de 2005, 42 pacientes foram submetidos a tratamento endovascular de doenças da aorta, sendo 25 por aneurismas de aorta abdominal (AAA). A idade média foi de 74 ± 10,2 anos e 92 por cento dos pacientes eram do sexo masculino. Os procedimentos foram realizados por uma equipe multidisciplinar, no Hospital de Clínicas de Porto Alegre e Hospital Luterano (ULBRA). Vinte e quatro pacientes foram submetidos à colocação de endoprótese bifurcada e um, reta. Em todos os pacientes, o procedimento foi realizado por dissecção das artérias femorais, em laboratório de hemodinâmica. Em nenhum caso houve necessidade de conversão para cirurgia aberta. RESULTADOS: Não houve óbito nesta série. Até 2 anos e 3 meses de acompanhamento, todos os pacientes estão vivos e 24 (96 por cento) livres de reintervenção relacionada ao aneurisma. Um (4 por cento) paciente necessitou novo procedimento endovascular por vazamento tipo I, um ano após, sendo colocadas três extensões. Dois outros necessitaram derivação femoro-femoral cruzada, um no momento do procedimento endovascular e o outro, 24 horas após, por apresentar isquemia de membro inferior direito. CONCLUSÃO: O tratamento endovascular dos AAA representa uma nova alternativa à cirurgia convencional, menos invasiva, principalmente para pacientes com alto risco cirúrgico. Como o procedimento é relativamente novo, estudos prospectivos e randomizados são necessários para avaliar resultados a longo prazo. Excelentes resultados a curto e médio prazo podem ser obtidos em nosso meio.

OBJECTIVE: The purpose of this study is to present the short and mid-term results of the endovascular treatment of abdominal aortic aneurysms (AAA). This is an initial experience of a multidisciplinary team. METHOD: Between July 2003 and October 2005, 42 patients (25 of whom suffered from AAAs) were treated with endovascular therapy for aortic diseases. The mean patient age was 74 ±10.2 years with 92 percent men. The endovascular precedures were performed by a multidisciplinary team in the Hospital de Clínicas de Porto Alegre and Hospital Luterano (ULBRA). In twenty-four of the AAA patients, bifurcated grafts were used and only one had a straight graft. In all patients the procedure was carried out by femoral artery dissection in a catheterization laboratory. There was no need to convert to open repair. RESULTS: There were no operative or postoperative deaths. The survival rate free from reintervention is 96 percent after two years and three months. One (4 percent) patient needed a new endovascular procedure for type I endoleak one year after, and three extensions were used successfully. Two other patients needed femoro-femoral bypasses, one at the same time as the endovascular procedure and the other one 24 hours later because of lower limb ischemia. CONCLUSION: The endovascular treatment of AAAs represents a new less invasive alternative to conventional surgery, especially for high risk patients. Further prospective and randomized studies to evaluate the long term outcomes are needed. Excellent results in short and mid-terms can be obtained by a multidisciplinary teams in our country.

O polimorfismo 894G>T do gene da óxido nítrico sintase endotelial e sua associação com doença coronária / The 894G>T polymorphism of the endothelial constitutive nitric oxide synthase gene and its association with coronary artery disease

O endotélio cumpre um papel fundamental na vasodilatação fisiológica e na proteção da parede arterial frente aos processos de trombose e aterosclerose, assim como na resposta à lesão provocada pela angioplastia ou implante de stent intracoronário. Essa função protetora é exercida, entre outros mecanismos, através da síntese e liberação de óxido nítrico (NO) pela célula endotelial. O NO inibe a adesão e a agregação plaquetária, assim como provoca a desagregação de agregado plaquetário. Inibe também a mitogênese e a proliferação de células de músculo liso vascular, assim como a quimiotaxia e a adesão de polimorfonucleares neutrófilos ao endotélio. O NO é sintetizado na célula endotelial, a partir da L-Arginina, pela NO sintase endotelial constitutiva (NOSec), uma enzima constitutiva codificada por um gene localizado no cromossomo 7q35-36, contendo 26 éxons que ocupam 21 quilobases. Foram descritos alguns polimorfismos deste gene, entre os quais, o polimorfismo 894G>T, presente no éxon 7 do gene da NOSec. Este polimorfismo consiste na substituição de uma base guanina por uma timina no nucleotídeo 894 do gene; esta mutação resulta na substituição de um aminoácido glutamato por aspartato na posição 298 da NOSec (Glu298Asp). Nesta revisão, descreve-se a possível associação desse polimorfismo com a doença coronária, destacando algumas contribuições de nosso grupo de pesquisa.

The endothelium plays a major role in the physiological vasodilatation, in the protection of the arterial wall against atherosclerotic and thrombotic process, as well as in the response to vessel injury after coronary angioplasty and stenting. This protective function is mediated, among others, by the synthesis and release of nitric oxide (NO) by endothelial cells. The NO has been shown to inhibit platelet adhesion and aggregation, and also to stimulate disaggregation of preformed platelet aggregates. It also inhibits mitogenesis and the proliferation of vascular smooth muscle cells, as well as polymorphonuclear adhesion and chemotaxis. The NO is synthesized in the endothelial cell from L-arginine, by endothelial constitutive nitric oxide synthase (ecNOS), which is a constitutive enzyme codified by a gene located in locus 7q35-36, containing 26 exons that occupy 21 kilobases. Some polymorphisms in this gene have been described. Among these, the 894G>T polymorphism present in the exon 7 of the ecNOS gene. This polymorphism consists of the substitution of a guanine base by a thymine at nucleotide 894 of the gene; this mutation results in the substitution of the glutamate amino acid by aspartate at the 298th position of the ecNOS protein (Glu298Asp). In this review, we describe the possible association of this polymorphism with coronary artery disease and the contributions of our research group.

Plasma endothelin-1 levels after coronary stenting in humans.

Endothelin (ET)-1 levels were analyzed in patients who underwent elective coronary stenting. There was a significant increase in systemic ET-1 levels immediately after the procedure, which is probably a marker of endothelial dysfunction that is associated with arterial injury. However, there was no association between ET-1 levels and in-stent restenosis in humans.

Behavior of inflammatory markers of myocardial injury in cardiac surgery: laboratory correlation with the clinical picture of postpericardiotomy syndrome.

OBJECTIVE: To verify the association of serum markers of myocardial injury, such as troponin I, creatinine kinase, and creatinine kinase isoenzyme MB, and inflammatory markers, such as tumor necrosis factor alpha (TNF-alpha), C-reactive protein, and the erythrocyte sedimentation rate in the perioperative period of cardiac surgery, with the occurrence of possible postpericardiotomy syndrome. METHODS: This was a cohort study with 96 patients undergoing cardiac surgery assessed at the following 4 different time periods: the day before surgery (D0); the 3rd postoperative day (D3); between the 7th and 10th postoperative days (D7-10); and the 30th postoperative day (D30). During each period, we evaluated demographic variables (sex and age), surgical variables (type and duration, extracorporeal circulation), and serum dosages of the markers of myocardial injury and inflammatory response. RESULTS: Of all patients, 12 (12.5%) met the clinical criteria for a diagnosis of postpericardiotomy syndrome, and their mean age was 10.3 years lower than the age of the others (P=0.02). The results of the serum markers for tissue injury and inflammatory response were not significantly different between the 2 assessed groups. No significant difference existed regarding either surgery duration or extracorporeal circulation. CONCLUSION: The patients who met the clinical criteria for postpericardiotomy syndrome were significantly younger than the others were. Serum markers for tissue injury and inflammatory response were not different in the clinically affected group, and did not correlate with the different types and duration of surgery or with extracorporeal circulation.

Common variants in the lipoprotein lipase gene in Brazil: association with lipids and angiographically assessed coronary atherosclerosis.

Lipoprotein lipase is the rate-limiting enzyme in the lipolysis of plasma triglyceride-rich lipoproteins. We studied six variants (T-93G, D9N, N291S, PvuII, HindIII and S447X) in the lipoprotein lipase (LPL) gene in 309 non-diabetic patients with angiographically assessed coronary artery disease and in 197 controls in a southern Brazilian population of European descent. The HindIII H-allele was associated with lower triglycerides (p < 0.01) and higher high-density lipoprotein cholesterol (p = 0.03) levels, and the S447X mutation was associated with lower triglyceride levels (p < 0.01) in males, but not females. No other significant lipid associations were observed. Haplotypes were derived from these two sites (HindIII/S447X), and carriers of H-S and H-X haplotypes showed lower triglycerides (p < 0.01) and increased high-density lipoprotein cholesterol (p = 0.01) levels when compared to the H+S haplotype in males. In this gender, the H-X haplotype was associated with a protective effect (OR = 0.36, 95%CI = 0.13-0.97) for significant disease (> or = 60% of luminal coronary stenosis), even controlling for other classical risk factors.