Carlos V. Serrano

Hydrogen peroxide and superoxide modulate leukocyte adhesion molecule expression and leukocyte endothelial adhesion

While endothelial oxidant generation and subsequent leukocyte chemotaxis and activation are important mechanisms of tissue damage in ischemic organs, it is not known if oxidant generation may be involved in triggering the subsequent leukocyte-mediated injury which occurs. Questions remain whether particular oxidants and oxygen-free radicals are capable of modulating the expression of leukocyte adhesion molecules and effecting leukocyte endothelial adhesion. Studies were performed to determine the effect of different biologically occurring oxidant molecules and oxygen free radicals including: .O2-, .OH, and H2O2 on the expression of integrin and selectin adhesion molecules on the surface of human PMNs and to determine the effect of these alterations on PMN adhesion to the endothelium. Adhesion molecule expression on the surface of human PMNs was measured by immunofluorescence flow cytometry. Electron paramagnetic resonance spectroscopy was applied to characterize the presence of exogenous free radical generation as well as that from activated PMNs. It was observed that these oxidants can cause up-regulation of CD11b and CD18 expression with shedding of L-selectin. The kinetics and dose-response of these effects were analyzed and their functional significance determined by measuring PMN adhesion to cultured human aortic endothelial monolayers. These studies demonstrate that oxygen free radicals and non-radical oxidants can directly trigger PMN activation and adhesion to vascular endothelium.

Cardioprotective actions of a monoclonal antibody against CD-18 in myocardial ischemia-reperfusion injury.

BackgroundPrevious studies have demonstrated that polymorphonuclear leukocytes (PMNs) are locally activated in reperfused myocardium and contribute to the myocardial cell injury associated with reperfusion. It has been suggested that the adhesion of activated PMNs in reperfused myocardium is mediated by the PMN adhesion molecule CD-18. In the present study, we performed experiments to determine if the specific anti-CD-18 monoclonal antibody (MAb) R15.7 can prevent PMN adhesion and PMN-mediated reperfusion injury in the heart. Methods and ResultsStudies were performed with isolated, Langendorff-perfused rat hearts (nine per group) in which the hearts were subjected to 20 minutes of global ischemia followed by 45 minutes of reperfusion. Human PMNs (50 million) and rat plasma (HNRP) were infused directly into the coronary circulation of nonischemic and postischemic hearts. When HNRP was administered to nonischemic hearts, no significant alterations in coronary flow, left ventricular developed pressure, or left ventricular end-diastolic pressure were observed. When hearts were reperfused in the presence of HNRP, however, marked impairment of contractile function was observed with more than 90%o reduction in coronary flow throughout the reperfusion period (P<.001 versus baseline). In addition, left ventricular developed pressure was significantly depressed (P<.001 versus baseline) throughout the reperfusion period in the HNRP group and recovered to only 13.0±3.0%o at 45 minutes of reperfusion. Moreover, left ventricular end-diastolic pressure was significantly elevated (P<.001) in the HNRP group throughout the reperfusion period. Treatment with the anti-CD-18 monoclonal antibody MAb R15.7 (20 pug/mL) at the time of reperfusion resulted in a 92.9±4.9%o recovery of coronary flow (P<.001 versus HNRP) as well as a 71.0±10.1% recovery of left ventricular developed pressure (P<.001 versus HNRP). Administration of MAb R15.7 also very significantly attenuated the elevation in left ventricular end-diastolic pressure that was observed in the untreated HNRP (30.2±7.8 versus 110.3±10.3 mm Hg, p<.001) at 45 minutes of reperfusion. Cardiac myeloperoxidase activity, an index of PMN accumulation, was markedly reduced in the MAb R15.7 group at 45 minutes of reperfusion compared with the HNRP group (0.03±0.01 versus 0.3±0.05, p<.001). To determine that the protective effect ofMAb R15.7 was based on functional blocking of CD-18, additional experiments were performed with identical concentrations of MAb 3.1, which binds to the a-subunit of LFA-1. This PMN-binding but non-CD-18-blocking antibody had little effect on the recovery of postischemic function or coronary flow and did not reduce tissue myeloperoxidase activity ConclusionsThe administration of a specific anti-CD-18 monoclonal antibody, MAb R15.7, attenuates much of the PMN-mediated contractile dysfunction associated with this in vitro model of myocardial ischemia-reperfusion injury by limiting PMN accumulation. We conclude that CD-18-mediated adhesion may play a critical role in the pathogenesis of PMN-induced myocardial injury.

Association between depression and development of coronary artery disease: pathophysiologic and diagnostic implications.

Depression and coronary artery disease (CAD) are both extremely prevalent diseases. In addition, compromised quality of life and life expectancy are characteristics of both situations. There are several conditions that aggravate depression and facilitate the development of CAD, as well as provoke a worse prognosis in patients with already established CAD: inferior adherence to medical orientations (medications and life style modifications), greater platelet activation and aggregation, endothelial dysfunction, and impaired autonomic dysfunction (lowered heart rate variability). Recent literature has shown that depression alone is becoming an independent risk factor for cardiac events both in primary and secondary prevention. As the diagnosis of depression in patients with heart disease is difficult, due to similarities of symptoms, the health professional should perform a careful evaluation to differentiate the clinical signs of depression from those related with general heart diseases. After a myocardial infarction, depression is an independent risk factor for mortality. Successful therapy of depression has been shown to improve patients’ quality of life and cardiovascular outcome. However, multicentric clinical trials are needed to support this inference. A practical liaison between qualified professionals is necessary for the better management of depressed patients with excess risk in developing CAD. Accordingly, pathophysiological and clinical implications between depression and CAD are discussed in this article.

The role of gender in the long-term prognosis of patients with myocardial infarction submitted to fibrinolytic treatment.

PURPOSEnTo determine the role of gender in short- and long-term survival after a thrombolytic-treated myocardial infarction.nnnMETHODSnA total of 686 consecutive patients with ST-elevation acute myocardial infarction, admitted to a single center and treated with intravenous streptokinase, were studied prospectively and consecutively. Assessment of clinical and in-hospital variables permitted comparison of baseline characteristics and both in-hospital and long-term survival between men and women.nnnRESULTSnA significantly (odds ratio=0.48, P=0.009) lower 14-day mortality rate for males (8.5%) relative to females (16%) was noted. However, this difference became non-significant after adjustment for age (odds-ratio male/female=0.62, P=0.097) or age and other variables (odds ratio=0.71, P=0.17). At the end of the follow-up (up to 12 years), survival rates for the whole population were 59.6% and 54.4% for men and women, respectively (chi-square=1.4, P=0.24); excluding in-hospital deaths, the rates were 65.1% and 64.8%, respectively (chi-square=0.21, P=0.65).nnnCONCLUSIONSnIn the short-term follow-up, women have a significantly higher mortality relative to men in an unadjusted analysis. This difference became non-significant after adjusting for age, or age and other variables. In the long-term follow-up, sex was not correlated with prognosis.

Infarto agudo do miocárdio: síndrome coronariana aguda com supradesnível do segmento ST

Cardiovascular diseases continue to be the first cause of death in Brazil - responsible for almost 32% of all deaths. In addition, they are the third major cause of admission in the country. Among them, acute myocardial infarction is still one of the major causes of morbidity and mortality. Despite of the last decades therapeutic advances, acute myocardial infarction still shows remarkable rates of mortality, and great part of the patients do not receive the adequate treatment. The opening of the Coronary Care Units and the introduction of reperfusion treatment with fibrinolytics or primary angioplasty were fundamental to reduce mortality and complications related to myocardial infarction. Important beneficial effects to the current treatment include less ventricular dysfunction and better control of ventricular arrhythmias. The need of early reperfusion is crucial for the good prognosis after a myocardial infarction. The objective of this review is to emphasize the modern basic concepts of the pathophysiology, diagnosis and treatment of acute myocardial infarction, according to national and international guidelines.

Cardiovascular risks of androgen deprivation therapy

O adenocarcinoma de prostata e o câncer mais comum no sexo masculino apos o câncer de pele. Entre as varias formas de tratamento do câncer de prostata, a terapia de bloqueio androgenico e uma modalidade consagrada nos pacientes com doenca metastatica ou localmente avancada, que provavelmente resulta em aumento de sobrevida. No entanto, o bloqueio androgenico e causador de uma serie de consequencias adversas. Complicacoes como osteoporose, disfuncao sexual, ginecomastia, anemia e alteracoes na composicao corporal sao bem conhecidas. Recentemente, uma serie de complicacoes metabolicas foi descrita como aumento da circunferencia abdominal, resistencia a insulina, hiperglicemia, diabete, dislipidemia e sindrome metabolica com consequente aumento do risco de eventos coronarianos e mortalidade cardiovascular nessa populacao especifica. Este artigo de atualizacao apresenta uma revisao bibliografica realizada no MEDLINE de toda literatura publicada em ingles no periodo de 1966 ate junho de 2009, com as seguintes palavras-chave: androgen deprivation therapy, androgen supression therapy, hormone treatment, prostate cancer, metabolic syndrome e cardiovascular disease, no intuito de analisar quais seriam os reais riscos cardiovasculares da terapia de deprivacao androgenica, tambem chamada bloqueio androgenico, nos pacientes com câncer de prostata.Prostate adenocarcinoma is the most common cancer type in the male sex after skin cancer. Among the several types of treatment for prostate cancer, the androgen deprivation therapy has been highly recommended in patients with metastatic or locally advanced disease, which probably results in increased survival. However, the androgen deprivation is the cause of several adverse effects. Complications such as osteoporosis, sexual dysfunction, gynecomastia, anemia and body composition alterations are well-known effects of the therapy. Recently, a number of metabolic complications have been described, such as increase in the abdominal circumference, insulin resistance, hyperglycemia, diabetes, dyslipidemia and metabolic syndrome, with a consequent increase in the risk of coronary events and cardiovascular mortality in this specific population. This update article presents a literature review carried out at MEDLINE database of all literature published in English from 1966 to June 2009, using the following key words: androgen deprivation therapy, androgen suppression therapy, hormone treatment, prostate cancer, metabolic syndrome and cardiovascular disease, with the objective of analyzing which would be the actual cardiovascular risks of androgen deprivation therapy, also called androgen suppression, in patients with prostate cancer.

Intracardiac embolization of inferior vena cava filter associated with right atrium perforation and cardiac tamponade

Insertion of inferior vena cava filters has been well established in literature, reducing occurrence of pulmonary embolism after an episode of deep venous thrombosis in patients with contraindication to anticoagulation. There are a small number of complications related to procedure and embolization is rare. In this context, we described a case of intracardiac embolization associated with cardiac tamponade.

Takayasu arteritis: stenosis after bare-metal and drug-eluting stent implantation

Introducao Arterite de Takayasu (AT) e uma arterite inflamatoria cronica de etiologia desconhecida que acomete grandes vasos, principalmente aorta e seus principais ramos, vasos pulmonares e coronarias1. Devido a raridade dos casos a monitoracao da atividade da doenca e o melhor esquema terapeutico ainda tem sido um desafio para todos os que tratam esses pacientes. Especificamente em casos de sindromes coronarias agudas (SCA), a melhor forma de tratamento intervencionista mantem-se indefinido. Algumas series de casos apresentam sua experiencia com angioplastia coronaria (ATC) e/ou cirurgia de revascularizacao miocardica (CRM), porem com pouca consistencia1. Nesse contexto, o relato da evolucao de uma mesma paciente submetida a implante de stent coronario convencional e, posteriormente, farmacologico de forma consecutiva, associado a estenose coronaria intrastent nos dois procedimentos na ausencia de inflamacao, com subsequente realizacao de CRM, e unico e reforca a dificuldade de manejo de SCA nessa doenca.

THE PROGNOSTIC VALUE OF DIABETES AND OF ACUTE HYPERGLYCEMIA IS DIFFERENT DURING THE IN-HOSPITAL AND CHRONIC PHASES AFTER MYOCARDIAL INFARCTION

THE PROGNOSTIC VALUE OF DIABETES AND OF ACUTE HYPERGLYCEMIA IS DIFFERENT DURING THE IN-HOSPITAL AND CHRONIC PHASES AFTER MYOCARDIAL INFARCTION José C. Nicolau, Felipe G. Lima, Marcelo Franken, Carlos V. Serrano Jr., Roberto R. Giraldez, Luciano M. Baracioli, Fernando Ganem, Caio F. Fernandes, Karin D. Campos, Thiago F. Pinto, José A.F. Ramires Background: Diabetes (DM) and hyperglycemia are both powerful risk factors for pts with acute myocardial infarction (AMI). However, the relationship between them and their individual role during the in-hospital phase and in the long-term after hospital discharge are not clearly understood. Methods: We analyzed retrospectively 1429 pts with AMI (mean age 64.5 + 0.34 y.o., 72.5% men) treated in a single tertiary institution, included prospectively in a dedicated databank and followed for up to 11.7 years (mean survival time=8.7 years). Correlations with mortality were carried out utilizing the Chi-square/log-rank tests and logistical/Cox stepwise regression models as indicated. Results: (1) In-hospital phase: Death rates for diabetics and nondiabetics were, respectively, 12.7% and 9.6% (P=0.08); by univariate logistic regression, glucose level (as continuous variable) at hospital arrival was highly correlated with mortality (P<0.001); putting together both variables in a multivariate model, the figures were P=0.74 for DM and P<0.001 for glucose level (GL); in the adjusted model with 15 baseline variables included, GL remained correlating significantly with mortality (P<0.001), along with age (P<0.001), ST-elevation AMI (P=0.03), and history of heart failure (P<0.001) and hypertension (P=0.005). (2) Long-term outcome: The mean survival time for nondiabetics and diabetics were, respectively, 9.02 and 7.88 years (P<0.001); GL showed a borderline correlation with mortality (P=0.046); with both variables in the same model, the figures were P= 0.001 for DM and P=0.75 for GL; in the multivariate model with all 15 variables included, history of DM remained correlating significantly with mortality (P=0.022), along with age (P<0.001) and history of previous AMI (P<0.001), heart failure (P=0.01) and stroke (P=0.013). In a multivariate model excluding in-hospital deaths, DM remained correlating significantly with mortality (P=0.041). Conclusions: During the in-hospital phase the glucose level at hospital arrival is a better mortality predictor than DM; on the other hand, DM is a good mortality predictor in the long-term follow up after AMI, contrary to glucose level.

Riscos cardiovasculares do bloqueio androgênico

O adenocarcinoma de prostata e o câncer mais comum no sexo masculino apos o câncer de pele. Entre as varias formas de tratamento do câncer de prostata, a terapia de bloqueio androgenico e uma modalidade consagrada nos pacientes com doenca metastatica ou localmente avancada, que provavelmente resulta em aumento de sobrevida. No entanto, o bloqueio androgenico e causador de uma serie de consequencias adversas. Complicacoes como osteoporose, disfuncao sexual, ginecomastia, anemia e alteracoes na composicao corporal sao bem conhecidas. Recentemente, uma serie de complicacoes metabolicas foi descrita como aumento da circunferencia abdominal, resistencia a insulina, hiperglicemia, diabete, dislipidemia e sindrome metabolica com consequente aumento do risco de eventos coronarianos e mortalidade cardiovascular nessa populacao especifica. Este artigo de atualizacao apresenta uma revisao bibliografica realizada no MEDLINE de toda literatura publicada em ingles no periodo de 1966 ate junho de 2009, com as seguintes palavras-chave: androgen deprivation therapy, androgen supression therapy, hormone treatment, prostate cancer, metabolic syndrome e cardiovascular disease, no intuito de analisar quais seriam os reais riscos cardiovasculares da terapia de deprivacao androgenica, tambem chamada bloqueio androgenico, nos pacientes com câncer de prostata.Prostate adenocarcinoma is the most common cancer type in the male sex after skin cancer. Among the several types of treatment for prostate cancer, the androgen deprivation therapy has been highly recommended in patients with metastatic or locally advanced disease, which probably results in increased survival. However, the androgen deprivation is the cause of several adverse effects. Complications such as osteoporosis, sexual dysfunction, gynecomastia, anemia and body composition alterations are well-known effects of the therapy. Recently, a number of metabolic complications have been described, such as increase in the abdominal circumference, insulin resistance, hyperglycemia, diabetes, dyslipidemia and metabolic syndrome, with a consequent increase in the risk of coronary events and cardiovascular mortality in this specific population. This update article presents a literature review carried out at MEDLINE database of all literature published in English from 1966 to June 2009, using the following key words: androgen deprivation therapy, androgen suppression therapy, hormone treatment, prostate cancer, metabolic syndrome and cardiovascular disease, with the objective of analyzing which would be the actual cardiovascular risks of androgen deprivation therapy, also called androgen suppression, in patients with prostate cancer.