Endurance training modulates lymphocyte function in rats with post-MI CHF

Purpose: Exercise training restores innate immune system cell function in post-myocardial infarction (post-MI) rats. However, studies of the involvement of lymphocyte (Ly) in the setting of the congestive heart failure (CHF) are few. To address this issue, we investigated the function of Ly obtained from cervical lymph nodes from post-MI CHF rats submitted to treadmill running training. Methods: Twenty-five male Wistar rats were randomly assigned to the following groups: rats submitted to ligation of the left coronary artery, which were sedentary (MI-S, N= 7, only limited activity) or trained (MI-T, N= 6, on a treadmill (0% grade at 13-20 m.m(-1)) for 60 min.d(-1), 5 d.wk(-1), for 8-10 wk); or sham-operated rats, which were sedentary (sham-S, N = 6) or trained (sham-T, N = 6). The incorporation of [2-C-14]-thymidine by Ly cultivated in the presence of concanavalin A (Con A) and lipopolysaccharide (LPS), cytokine production by Ly cultivated in the presence of phytohemagglutinin (PHA), and plasma concentration of glutamine were assessed in all groups, 48 h after the last exercise session. Results: Proliferative capacity was increased, following incubation with Con-A in the MI groups, when compared with the sham counterparts. When incubated in the presence of PHA, MI-S produced more IL-4 (96%) than sham-S (P < 0.001). The training protocol induced a 2.2-fold increase in the production of interleukin-2 (P < 0.001) of the cells obtained from the cervical lymph nodes of MI-T, compared with MI-S. Conclusion: The moderate endurance training protocol caused an increase in IL-2 production, and a trend toward the reversion of the Th-1/Th-2 imbalance associated with IL-4 production increased in the post-MI CHF animal model.

TUMOR NECROSIS FACTOR IS NOT ASSOCIATED WITH INTESTINAL ISCHEMIA/REPERFUSION-INDUCED LUNG INFLAMMATION

Intestinal ischemia-reperfusion (I/R) injury may cause acute systemic and lung inflammation. Here, we revisited the role of TNF-alpha in an intestinal I/R model in mice, showing that this cytokine is not required for the local and remote inflammatory response upon intestinal I/R injury using neutralizing TNF-alpha antibodies and TNF ligand-deficient mice. We demonstrate increased neutrophil recruitment in the lung as assessed by myeloperoxidase activity and augmented IL-6, granulocyte colony-stimulating factor, and KC levels, whereas TNF-alpha levels in serum were not increased and only minimally elevated in intestine and lung upon intestinal I/R injury. Importantly, TNF-alpha antibody neutralization neither diminished neutrophil recruitment nor any of the cytokines and chemokines evaluated. In addition, the inflammatory response was not abrogated in TNF and TNF receptors 1 and 2-deficient mice. However, in view of the damage on the intestinal barrier upon intestinal I/R with systemic bacterial translocation, we asked whether Toll-like receptor (TLR) activation is driving the inflammatory response. In fact, the inflammatory lung response is dramatically reduced in TLR2/4-deficient mice, confirming an important role of TLR receptor signaling causing the inflammatory lung response. In conclusion, endogenous TNF-alpha is not or minimally elevated and plays no role as a mediator for the inflammatory response upon ischemic tissue injury. By contrast, TLR2/4 signaling induces an orchestrated cytokine/chemokine response leading to local and remote pulmonary inflammation, and therefore disruption of TLR signaling may represent an alternative therapeutic target.

Upregulation of gp91(phox) Subunit of NAD(P)H Oxidase Contributes to Erectile Dysfunction Caused by Long-term Nitric Oxide Inhibition in Rats: Reversion by Regular Physical Training

OBJECTIVES To test the hypothesis that glyco protein 91phox (gp91(phox)) subunit of nicotinamide adenine dinucleotide phosphate [NAD(P) H] oxidase is a fundamental target for physical activity to ameliorate erectile dysfunction (ED). Vascular risk factors are reported to contribute to ED. Regular physical exercise prevents cardiovascular diseases by increasing nitric oxide (NO) production and/or decreasing NO inactivation. METHODS Male Wistar rats received the NO synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) for 4 weeks, after which animals were submitted to a run training program for another 4 weeks. Erectile functions were evaluated by in vitro cavernosal relaxations and intracavernous pressure measurements. Expressions of gp91(phox) subunit and neuronal nitric oxidase synthase in erectile tissue, as well as superoxide dismutase activity and nitrite/nitrate (NO(x)) levels were determined. RESULTS The in vitro acetylcholine-and electrical field stimulation-induced cavernosal relaxations, as well as the increases in intracavernous pressure were markedly reduced in sedentary rats treated with L-NAME. Run training significantly restored the impaired cavernosal relaxations. No alterations in the neuronal nitric oxidase synthase protein expression (and its variant penile neuronal nitric oxidase synthase) were detected. A reduction of NO(x) levels and superoxide dismutase activity was observed in L-NAME-treated animals, which was significantly reversed by physical training. Gene expression of subunit gp91(phox) was enhanced by approximately 2-fold in erectile tissue of L-NAME-treated rats, and that was restored to basal levels by run training. CONCLUSIONS Our study shows that ED seen after long-term L-NAME treatment is associated with gp91(phox) subunit upregulation and decreased NO bioavailability. Exercise training reverses the increased oxidative stress in NO-deficient rats, ameliorating the ED. UROLOGY 75: 961-967, 2010. (C) 2009 Elsevier Inc.

NITRIC OXIDE MEDIATES LUNG VASCULAR PERMEABILITY AND LYMPH-BORNE IL-6 AFTER AN INTESTINAL ISCHEMIC INSULT

Acute lung injury following intestinal I/R depends on neutrophil-endothelial cell interactions and on cytokines drained from the gut through the lymph. Among the mediators generated during I/R, increased serum levels of IL-6 and NO are also found and might be involved in acute lung injury. Once intestinal ischemia itself may be a factor of tissue injury, in this study, we investigated the presence of IL-6 in lymph after intestinal ischemia and its effects on human umbilical vein endothelial cells (HUVECs) detachment. The involvement of NO on the increase of lung and intestinal microvascular permeability and the lymph effects on HUVEC detachment were also studied. Upon anesthesia, male Wistar rats were subjected to occlusion of the superior mesenteric artery during 45 min, followed by 2-h intestinal reperfusion. Rats were treated with the nonselective NO synthase (NOS) inhibitor L-NAME (N(omega)-nitro-L-arginine methyl ester) or with the selective inhibitor of iNOS aminoguanidine 1 h before superior mesenteric artery occlusion. Whereas treatment with L-NAME during ischemia increased both IL-6 levels in lymph and lung microvascular permeability, aminoguanidine restored the augmented intestinal plasma extravasation due to ischemia and did not induce IL-6 in lymph. On the other hand, IL-6 and lymph of intestinal I/R detached the HUVECs, whereas lymph of ischemic rats upon L-NAME treatment when incubated with anti-IL-6 prevented HUVEC detachment. It is shown that the intestinal ischemia itself is sufficient to increase intestinal microvascular permeability with involvement of iNOS activation. Intestinal ischemia and absence of constitutive NOS activity leading to additional intestinal stress both cause release of IL-6 and increase of lung microvascular permeability. Because anti-IL-6 prevented the endothelial cell injury caused by lymph at the ischemia period, the lymph-borne IL-6 might be involved with endothelial cell activation. At the reperfusion period, this cytokine does not seem to be modulated by NO.

The renin-angiotensin system is modulated by swimming training depending on the age of spontaneously hypertensive rats

Aim: To investigate the effects of swimming training on the renin-angiotensin system (RAS) during the development of hypertensive disease. Main methods: Male spontaneously hypertensive rats (SHR) were randomized into: sedentary young (SY), trained young (TV), sedentary adult (SA), and trained adult (TA) groups. Swimming was performed 5 times/wk/8wks. Key findings: Trained young and adult rats showed both decreased systolic and mean blood pressure, and bradycardia after the training protocol. The left ventricular hypertrophy (LVH) was observed only in the TA group (12.7%), but there was no increase on the collagen volume fraction. Regarding the components of the RAS, TV showed lower activity and gene expression of angiotensinogen (AGT) compared to SY. The TA group showed lower activity of circulatory RAS components, such as decreased serum ACE activity and plasma renin activity compared to SA. However, depending on the age, although there were marked differences in the modulation of the RAS by training, both trained groups showed a reduction in circulating angiotensin II levels which may explain the lower blood pressure in both groups after swimming training. Significance: Swimming training regulates the RAS differently in adult and young SHR rats. Decreased local cardiac RAS may have prevented the LVH exercise-induced in the TV group. Both groups decreased serum angiotensin II content, which may, at least in part, contribute to the lowering blood pressure effect of exercise training. (C) 2011 Elsevier Inc. All rights reserved.

Autoantibody response to chromatographic fractions from oxidized LDL in unstable angina patients and healthy controls

Levels of autoantibodies to oxidized low-density lipoprotein (oxLDL) have been correlated to atherosclerosis; however, contradictory results have been shown. To better understand the role of autoantibodies to oxLDL in atherogenesis, and their potential to predict risk of developing coronary artery disease we investigated the antibody response of unstable angina (UA) patients and healthy controls against chromatographic separated fractions of oxLDL. Five major peaks were detected after chromatographic separation of oxLDL and 10 fractions were collected. Surprisingly, when the response to high molecular weight fractions was analysed, we observed a significant increase in the levels of autoantibodies in controls compared to UA. In contrast, when the autoantibody response to intermediate and low molecular weight fractions was analysed, we observed that the UA group showed consistently higher levels compared with controls. Our data demonstrates that within oxLDL there are major fractions that can be recognized by autoantibodies from either UA patients or healthy individuals, and that the use of total oxLDL as an antigen pool may mask the presence of some antigenic molecules and their corresponding antibodies. Further studies are needed, but the analysis of antibody profiles may indeed open up a novel approach for evaluation and prevention against atherosclerosis.

Angiotensin II modulates CD40 expression in vascular smooth muscle cells

The signalling pathway CD40/CD40L (CD40 ligand) plays an important role in atherosclerotic plaque formation and rupture. AngII (angiotensin II), which induces oxidative stress and inflammation, is also implicated in the progression of atherosclerosis. In the present study, we tested the hypothesis that AngII increases CD40/CD40L activity in vascular cells and that ROS (reactive oxygen species) are part of the signalling cascade that controls CD40/CD40L expression. Human CASMCs (coronary artery smooth muscle cells) in culture exposed to IL (interleukin)-1 beta or TNF-alpha (tumour necrosis factor-a) had increased superoxide generation and enhanced CD40 expression, detected by EPR (electron paramagnetic resonance) and immunoblotting respectively. Both phenomena were abolished by previous incubation with membrane-permeant antioxidants or cell transfection with P22(phox) antisense. AngII (50-200 nmol/l) induced an early and sustained increase in CD40 mRNA and protein expression in CASMCs, which was blocked by treatment with antioxidants. Increased CD40 expression led to enhanced activity of the pathway, as AngII-treated cells stimulated with recombinant CD40L released higher amounts of IL-8 and had increased COX-2 (cyclo-oxygenase-2) expression. We conclude that AngII stimulation of vascular cells leads to a ROS-dependent increase in CD40/CD40L signalling pathway activity. This phenomenon may be an important mechanism modulating the arterial injury observed in atherosclerosis-related vasculopathy.

Enhancement on the Europium emission band of Europium chlortetracycline complex in the presence of LDL

Low-density lipoprotein (LDL) particles are the major cholesterol-carrying lipoprotein in the human circulation from the liver to peripheral tissues. High levels of LDL-Cholesterol (LDL-C) are known risk factor for the development of coronary artery disease (CAD). The most common approach to determine the LDLC in the clinical laboratory involves the Friedewald formula. However, in certain situations, this approach is inadequate. In this paper we report on the enhancement on the Europium emission band of Europium chlortetracycline complex (CTEu) in the presence of LDL. The emission intensity at 615 nm of the CTEu increases with increasing amounts of LDL. This phenomenon allowed us to propose a method to determine the LDL concentration in a sample composed by an aqueous solution of LDL. With this result we obtained LDL calibration curve, LOD (limit of detection) of 0.49 mg/mL and SD (standard deviation) of 0.003. We observed that CTEu complex provides a wider dynamic concentration-range for LDL determination than that from Eu-tetracycline previously. The averaged emission lifetimes of the CTEu and CTEu with LDL (1.5 mg/mL) complexes were measured as 15 and 46 Its, respectively. Study with some metallic interferents is presented. (C) 2010 Elsevier Inc. All rights reserved.

Early Increase in Autoantibodies Against Human Oxidized Low-Density Lipoprotein in Hypertensive Patients After Blood Pressure Control

BACKGROUND Oxidized lipoproteins and antioxidized low-density lipoprotein (anti-oxLDL) antibodies (Abs) have been detected in plasma in response to blood pressure (BP) elevation, suggesting the participation of the adaptive immune system. Therefore, treatment of hypertension may act on the immune response by decreasing oxidation stimuli. However, this issue has not been addressed. Thus, we have here analyzed anti-oxLDL Abs in untreated (naive) hypertensive patients shortly after initiation of anti hypertensive therapeutic regimens. METHODS Titers of anti-oxLDL Abs were measured in subjects with recently diagnosed hypertension on stage 1 (n = 94), in primary prevention of coronary disease, with no other risk factors, and naive of anti hypertensive medication at entry. Subjects were randomly assigned to receive perindopril, hydrochlorothiazide (HCTZ), or indapamide (INDA) for 12 weeks, with additional perindopril if necessary to achieve BP control. Abs against copper-oxidized LDL were measured by enzyme-linked immunosorbent assay. RESULTS Twelve-week antihypertensive treatment reduced both office-based and 24-h ambulatory BP measurements (P < 0.0005). The decrease in BP was accompanied by reduction in thiobarbituric acid-reactive substances (TBARS) (P < 0.05), increase in anti-oxLDL Ab titers (P < 0.005), and improvement in flow-mediated dilation (FMD) (P < 0.0005), independently of treatment. Although BP was reduced, we observed favorable changes in anti-oxLDL titers and FMD. CONCLUSIONS We observed that anti-oxLDL Ab titers increase after antihypertensive therapy in primary prevention when achieving BP targets. Our results are in agreement with the concept that propensity to oxidation is increased by essential hypertension and anti-oxLDL Abs may be protective and potential biomarkers for the follow-up of hypertension treatment.

Investigation of the Europium Emission Spectra of the Europium-Oxytetracycline Complex in the Presence of Human Low-Density Lipoproteins

Low-Density Lipoprotein (LDL), often known as ""bad cholesterol"" is one of the responsible to increase the risk of coronary arterial diseases. For this reason, the cholesterol present in the LDL particle has become one of the main parameters to be quantified in routine clinical diagnosis. A number of tools are available to assess LDL particles and estimate the cholesterol concentration in the blood. The most common methods to quantify the LDL in the plasma are the density gradient ultracentrifugation and nuclear magnetic resonance (NMR). However, these techniques require special equipments and can take a long time to provide the results. In this paper, we report on the increase of the Europium emission in Europium-oxytetracycline complex aqueous solutions in the presence of LDL. This increase is proportional to the LDL concentration in the solution. This phenomenum can be used to develop a method to quantify the number of LDL particles in a sample. A comparison between the performances of the oxytetracycline and the tetracycline in the complexes is also made.

Cardiovascular Disease Parameters in Periodontitis

Background: Recently, there has been an increasing in the impact of oral health on atherosclerosis and subsequent cardiovascular disease. The aim of this study is to investigate the association between chronic periodontitis and cardiovascular risk markers. Methods: Forty patients with periodontitis and 40 healthy gender-, body mass index-, and age-matched individuals were compared by measuring total cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, levels of cytokines, antibodies against oxidized low-density lipoprotein, thiobarbituric acid reactive substances, total and differential white blood cell counts, and the non-linear index of refraction. Results: The levels of triglycerides and high-density lipoprotein in periodontitis patients were significantly higher and lower, respectively (P=0.002 and P=0.0126), compared to controls. Total cholesterol, low-density lipoprotein, and lipid peroxide levels were the same in both groups (P = 0.2943, P = 0.1284, and P = 0.067, respectively). Interleukin (IL)-6 and -8, antibodies against oxidized low-density lipoprotein, and leukocyte and neutrophil counts were significantly higher in periodontitis patients (P<0.05). The value of the non-linear index of refraction of low-density lipoprotein solutions was higher in the controls (P = 0.015) compared to individuals with periodontitis. Conclusion: Our results confirmed and further strengthened the suggested association between coronary artery disease and periodontitis. J Periodontol 2009;80:378-388.

Evidence that OGG1 glycosylase protects neurons against oxidative DNA damage and cell death under ischemic conditions

7,8-Dihydro-8-oxoguanine DNA glycosylase (OGG1) is a major DNA glycosylase involved in base-excision repair (BER) of oxidative DNA damage to nuclear and mitochondrial DNA (mtDNA). We used OGG1-deficient (OGG1(-/-)) mice to examine the possible roles of OGG1 in the vulnerability of neurons to ischemic and oxidative stress. After exposure of cultured neurons to oxidative and metabolic stress levels of OGG1 in the nucleus were elevated and mitochondria exhibited fragmentation and increased levels of the mitochondrial fission protein dynamin-related protein 1 (Drp1) and reduced membrane potential. Cortical neurons isolated from OGG1(-/-) mice were more vulnerable to oxidative insults than were OGG1(+/+) neurons, and OGG1(-/-) mice developed larger cortical infarcts and behavioral deficits after permanent middle cerebral artery occlusion compared with OGG1(+/+) mice. Accumulations of oxidative DNA base lesions (8-oxoG, FapyAde, and FapyGua) were elevated in response to ischemia in both the ipsilateral and contralateral hemispheres, and to a greater extent in the contralateral cortex of OGG1(-/-) mice compared with OGG1(+/+) mice. Ischemia-induced elevation of 8-oxoG incision activity involved increased levels of a nuclear isoform OGG1, suggesting an adaptive response to oxidative nuclear DNA damage. Thus, OGG1 has a pivotal role in repairing oxidative damage to nuclear DNA under ischemic conditions, thereby reducing brain damage and improving functional outcome. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 680-692; doi:10.1038/jcbfm.2010.147; published online 25 August 2010

Contribuição da Endotelina-1 para o tônus coronariano de seres humanos: experimentos com o antagonista dos receptores ET-A

Introdução. A endotelina-1, o mais potente vasoconstritor endógeno, atua através de dois receptores de afinidades distintas, conhecidos como ETA e ETB. Os receptores ETA estão localizados predominantemente na musculatura lisa vascular e são os principais mediadores do efeito vasoconstritor da endotelina-1. Diversos estudos demonstraram que a endotelina-1 exerce um papel importante na manutenção do tônus arterial basal. Entretanto, a contribuição da endotelina-1 para o tônus coronariano basal em seres humanos, especialmente em coronárias com lesões ateroscleróticas, permanece alvo de interesse. Objetivos. Os objetivos deste estudo foram avaliar a contribuição da endotelina-1 no tônus coronariano epicárdico e na microcirculação em coronárias livres de lesões obstrutivas e em coronárias com lesões ateroscleróticas e comparar o método da contagem TIMI com o Doppler intracoronário na detecção de alterações do fluxo sangüíneo em resposta à adenosina. Métodos. Um total de 16 pacientes, sendo oito destes no grupo com coronárias livres de lesões obstrutivas e oito pacientes com lesões coronarianas obstrutivas, foram incluídos neste estudo. Todos pacientes receberam a infusão seletiva intracoronária de BQ-123, um inibidor específico dos receptores ETA da endotelina-1, durante 60 minutos. Adenosina e nitroglicerina foram administradas em bolus no tronco da coronária esquerda. O efeito do BQ-123 no diâmetro coronário epicárdico foi avaliado por angiografia quantitativa realizada a cada 15 minutos ao longo da infusão da droga. O efeito na microcirculação coronária foi avaliado por variações no fluxo sangüíneo medido por guia-Doppler e pelo método da contagem TIMI. Resultados. A infusão de BQ-123 resultou em aumento de 7% do diâmetro coronário e de 19% no fluxo sangüíneo volumétrico em pacientes com artérias livres de lesões obstrutivas (P < 0,001 para comparação com basal). O aumento do calibre do vaso ocorreu de forma progressiva e uniforme ao longo do vaso. Os pacientes com lesão aterosclerótica apresentaram um aumento de 16% (P < 0,001 para comparação com artérias livres de lesões obstrutivas) no diâmetro coronário e 28% no local da estenose. A velocidade do fluxo sangüíneo em coronárias livres de lesões obstrutivas não se alterou significativamente tanto na medida por Doppler como pelo método de contagem TIMI. Houve uma correlação de 0,67 (P < 0,05) entre o método da contagem TIMI e o Doppler para detecção de alterações na velocidade do fluxo sangüíneo em resposta à adenosina. Conclusões. A infusão seletiva intracoronária do inibidor específico dos receptores ETA da endotelina-1 em seres humanos pode ser feita de maneira segura. A endotelina-1 exerce um papel importante na manutenção do tônus coronariano basal em artérias livres de lesões obstrutivas, sendo responsável pela quase totalidade do tônus constritor aumentado presente em coronárias com lesões ateroscleróticas. O método da contagem TIMI apresenta uma boa correlação com o Doppler para medida do fluxo sangüíneo em condições de hiperêmia.

Estudo comparativo da viabilidade miocárdica em áreas dissinérgicas ao ecocardiograma basal : cintilografia tomográfica com Tecnécio 99m-mibi sob baixa dose de Dobutamina versus Tálio em repouso-redistribuição

A cintilografia com radioisótopos em repouso tem despertado muito interesse nos últimos anos para pesquisa da viabilidade miocárdica na disfunção isquêmica avançada do VE, porque esta pode ser reversível e porque há melhora prognóstica neste contexto. O objetivo desse trabalho é buscar identificar a acurácia da cintilografia tomográfica Tc-99m-Sestamibi, sob a infusão de dobutamina em baixa dose. Foram protocolados trinta pacientes que sofreram um infarto do miocárdio com padrão “Q”, com dissinergia ao ecocardiograma, e submetidos a estudos perfusionais em dias diferentes, com Tc-99m-Sestamibi − dobutamina e Tl-201 em repouso-redistribuição 4 horas, usado como padrão ouro. Não ocorreram complicações com nenhum paciente submetido ao protocolo do estudo. Os resultados revelaram: sensibilidade = 85%, especificidade = 87%, valor preditivo positivo = 96%, valor preditivo negativo = 65 % e acurácia de = 85,2%. A razão de probabilidade positiva foi de 6,68 e a razão de probabilidade negativa de 0,17. Confrontando-se nossos dados com uma metanálise de resultados para o Tc-99m-Sestamibi em repouso, a sensibilidade no presente estudo foi 85% vs. 81% e a especificidade de 87% vs. 60%. Em relação aos dados da literatura para Tl-201: 85% vs. 90% e 87% vs. 54%, sensibilidade e especificidade, respectivamente. Em conclusão, o Tc-99m-Sestamibi sob a infusão de dobutamina parece ser um método promissor para detectar viabilidade superior a esta modalidade de cintilografia em repouso, com valores preditivos comparáveis à literatura disponível para esse mesmo método: 85,2% vs. 87%, 96% vs. 90% e 65% vs. 83%, para acurácia, valor preditivo positivo e valor preditivo negativo, respectivamente.

Fatores de risco para morte em pacientes diabéticos e não diabéticos em tratamento hemodialítico

A mortalidade dos pacientes diabéticos, quando iniciam tratamento hemodialítico, ainda é muito elevada, significativamente maior do que a dos pacientes não diabéticos. As doenças cardíacas são a principal causa de morte nestes pacientes. O diabetes, por si só, está associado a uma alta prevalência de hipertensão, doença cardiovascular e insuficiência cardíaca, resultando em morbi-mortalidade significativas. Tradicionalmente, a mortalidade tem sido associada à cardiopatia isquêmica. A mortalidade cardiovascular, entretanto, não está relacionada apenas à isquemia, mas também à insuficiência cardíaca e à morte súbita. O objetivo deste estudo foi analisar o papel da doença cardiovascular como fator prognóstico para a morte de pacientes diabéticos e não diabéticos, que iniciam hemodiálise, levando em consideração outros fatores. Este foi um estudo prospectivo de uma coorte de 40 pacientes diabéticos e 28 não diabéticos, que iniciaram programa de hemodiálise, de agosto de 1996 a junho de 1999, em 5 hospitais de Porto Alegre, Brasil. O tempo total de acompanhamento foi de 4,25 anos. A avaliação inicial, realizada entre o 20 e o 30 mês de hemodiálise, incluiu: um questionário com características demográficas, história do diabetes e suas complicações, história de hipertensão e acidente vascular cerebral; o exame físico incluindo avaliação nutricional e exame oftalmológico; e avaliação laboratorial com medidas de parâmetros nutricionais, bioquímicos, hormonais, perfil lipídico, e controle metabólico do diabetes, além da avaliação da adequação da diálise. Para a avaliação cardiovascular foram utilizados: questionário Rose, ECG em repouso, cintilografia em repouso e sob dipiridamol, e ecocardiograma bi-dimensional e com Doppler. A mortalidade foi analisada ao final dos 51 meses, e as causas de morte, definidas pelos registros médicos, atestados de óbito ou informações do médico assistente ou familiar. Na análise estatística, foram empregados o teste t de Student, o qui-quadrado (χ2) ou teste exato de Fisher. Para a análise da sobrevida, o método de Kaplan-Meier foi utilizado, e, para identificar os principais fatores associados à mortalidade, construiu-se um modelo de regressão múltipla de Cox. O nÍvel de significância adotado foi de 5%. Ao final do estudo, os pacientes diabéticos tiveram um índice de mortalidade significativamente mais elevado do que os pacientes sem diabetes (47,5% vs. 7,1%; P=0,0013, log rank test). Na análise de Cox, o padrão pseudonormal ou restritivo de disfunção diastólica esteve associado a um risco de 3,2 (IC 95%:1,2-8,8; P=0,02), e a presença de diabetes, a um risco de 4,7 (IC 95%:1,03-21,4; P=0,04) para a morte. Concluiu-se que a disfunção diastólica do ventrículo esquerdo foi o principal preditor de mortalidade nesta coorte de pacientes que estão iniciando tratamento hemodialítico.