Diastolic function is associated with quality of life and exercise capacity in stable heart failure patients with reduced ejection fraction

Exercise capacity and quality of life (QOL) are important outcome predictors in patients with systolic heart failure (HF), independent of left ventricular (LV) ejection fraction (LVEF). LV diastolic function has been shown to be a better predictor of aerobic exercise capacity in patients with systolic dysfunction and a New York Heart Association (NYHA) classification ≥II. We hypothesized that the currently used index of diastolic function E/e' is associated with exercise capacity and QOL, even in optimally treated HF patients with reduced LVEF. This prospective study included 44 consecutive patients aged 55±11 years (27 men and 17 women), with LVEF<0.50 and NYHA functional class I-III, receiving optimal pharmacological treatment and in a stable clinical condition, as shown by the absence of dyspnea exacerbation for at least 3 months. All patients had conventional transthoracic echocardiography and answered the Minnesota Living with HF Questionnaire, followed by the 6-min walk test (6MWT). In a multivariable model with 6MWT as the dependent variable, age and E/e' explained 27% of the walked distance in 6MWT (P=0.002; multivariate regression analysis). No association was found between walk distance and LVEF or mitral annulus systolic velocity. Only normalized left atrium volume, a sensitive index of diastolic function, was associated with decreased QOL. Despite the small number of patients included, this study offers evidence that diastolic function is associated with physical capacity and QOL and should be considered along with ejection fraction in patients with compensated systolic HF.

Effect of felodipine on myocardial and renal injury induced by aldosterone-high salt hypertension in uninephrectomized rats

It has been recently shown that calcium channel blockers might have a protective effect on cardiac fibrogenesis induced by aldosterone. The objective of this study was to evaluate the protective effect of felodipine, a dihydropyridine calcium channel blocker, against heart and kidney damage caused by aldosterone-high sodium intake in uninephrectomized rats. Wistar rats were divided into three groups: CNEP (uninephrectomized + 1 percent NaCl in the drinking water, N = 9); ALDO (same as CNEP group plus continuous infusion of 0.75 µg/h aldosterone, N = 12); ALDOF (same as ALDO group plus 30 mg·kg-1·day-1 felodipine in the drinking water, N = 10). All results were compared with those of age-matched, untreated rats (CTL group, N = 10). After 6 weeks, tail cuff blood pressure was recorded and the rats were killed for histological analysis. Blood pressure (mmHg) was significantly elevated (P < 0.05) in ALDO (180 ± 20) and ALDOF (168 ± 13) compared to CTL (123 ± 12) and CNEP (134 ± 13). Heart damage (lesion scores - median and interquartile range) was 7.0 (5.5-8.0) in ALDO and was fully prevented in ALDOF (1.5; 1.0-2.0). Also, left ventricular collagen volume fraction ( percent) in ALDOF (2.9 ± 0.5) was similar to CTL (2.9 ± 0.5) and CNEP (3.4 ± 0.4) and decreased compared to ALDO (5.1 ± 1.6). Felodipine partially prevented kidney injury since the damage score for ALDOF (2.0; 2.0-3.0) was significantly decreased compared to ALDO (7.5; 4.0-10.5), although higher than CTL (null score). Felodipine has a protective effect on the myocardium and kidney as evidenced by decreased perivascular inflammation, myocardial necrosis and fibrosis.

Myocardial contractility of the isovolumetrically beating isolated rat heart

Several indexes of myocardial contractility have been proposed to assess ventricular function in the isovolumetrically beating isolated heart. However, the conclusions reached on the basis of these indexes may be influenced by ventricular geometry rather than contractility itself. The objective of the present study was to assess the performance of widely used contractility indexes in the isovolumetrically beating isolated heart in two experimental models of hypertrophy, the spontaneously hypertensive rat (SHR) and infrarenal aortocava fistula. Compared to normotensive controls (N = 8), SHRs with concentric hypertrophy (N = 10) presented increased maximum rate of ventricular pressure rise (3875 ± 526 vs 2555 ± 359 mmHg/s, P < 0.05) and peak of isovolumetric pressure (187 ± 11 vs 152 ± 11 mmHg, P < 0.05), and decreased developed stress (123 ± 20 vs 152 ± 26 g/cm², P < 0.05) and slope of stress-strain relationship (4.9 ± 0.42 vs 6.6 ± 0.77 g/cm²/ percent). Compared with controls (N = 11), rats with volume overload-induced eccentric hypertrophy (N = 16) presented increased developed stress (157 ± 38 vs 124 ± 22 g/cm², P < 0.05) and slope of stress-strain relationship (9 ± 2 vs 7 ± 1 g/cm²/ percent, P < 0.05), and decreased maximum rate of ventricular pressure rise(2746 ± 382 vs 3319 ± 352 mmHg, P < 0.05) and peak of isovolumetric pressure (115 ± 14 vs 165 ± 13 mmHg/s, P < 0.05). The results suggested that indexes of myocardial contractility used in experimental studies may present opposite results in the same heart and may be influenced by ventricular geometry. We concluded that several indexes should be taken into account for proper evaluation of contractile state, in the isovolumetrically beating isolated heart.

Food restriction induces in vivo ventricular dysfunction in spontaneously hypertensive rats without impairment of in vitro myocardial contractility

Cardiac structures, function, and myocardial contractility are affected by food restriction (FR). There are few experiments associating undernutrition with hypertension. The aim of the present study was to analyze the effects of FR on the cardiac response to hypertension in a genetic model of hypertension, the spontaneously hypertensive rat (SHR). Five-month-old SHR were fed a control or a calorie-restricted diet for 90 days. Global left ventricle (LV) systolic function was evaluated in vivo by transthoracic echocardiogram and myocardial contractility and diastolic function were assessed in vitro in an isovolumetrically beating isolated heart (Langendorff preparation). FR reduced LV systolic function (control (mean ± SD): 58.9 ± 8.2; FR: 50.8 ± 4.8 percent, N = 14, P < 0.05). Myocardial contractility was preserved when assessed by the +dP/dt (control: 3493 ± 379; FR: 3555 ± 211 mmHg/s, P > 0.05), and developed pressure (in vitro) at diastolic pressure of zero (control: 152 ± 16; FR: 149 ± 15 mmHg, N = 9, P > 0.05) and 25 mmHg (control: 155 ± 9; FR: 150 ± 10 mmHg, N = 9, P > 0.05). FR also induced eccentric ventricular remodeling, and reduced myocardial elasticity (control: 10.9 ± 1.6; FR: 9.2 ± 0.9 percent, N = 9, P < 0.05) and LV compliance (control: 82.6 ± 16.5; FR: 68.2 ± 9.1 percent, N = 9, P < 0.05). We conclude that FR causes systolic ventricular dysfunction without in vitro change in myocardial contractility and diastolic dysfunction probably due to a reduction in myocardial elasticity.

Lipid peroxidation, antioxidant enzymes and glutathione levels in human erythrocytes exposed to colloidal iron hydroxide in vitro

The free form of the iron ion is one of the strongest oxidizing agents in the cellular environment. The effect of iron at different concentrations (0, 1, 5, 10, 50, and 100 µM Fe3+) on the normal human red blood cell (RBC) antioxidant system was evaluated in vitro by measuring total (GSH) and oxidized (GSSG) glutathione levels, and superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) and reductase (GSH-Rd) activities. Membrane lipid peroxidation was assessed by measuring thiobarbituric acid reactive substance (TBARS). The RBC were incubated with colloidal iron hydroxide and phosphate-buffered saline, pH 7.45, at 37oC, for 60 min. For each assay, the results for the control group were: a) GSH = 3.52 + ou - 0.27 µM/g Hb; b) GSSG = 0.17 + ou - 0.03 µM/g Hb; c) GSH-Px = 19.60 + ou - 1.96 IU/g Hb; d) GSH-Rd = 3.13 + ou - 0.17 IU/g Hb; e) catalase = 394.9 + ou - 22.8 IU/g Hb; f) SOD = 5981 + ou - 375 IU/g Hb. The addition of 1 to 100 µM Fe3+ had no effect on the parameters analyzed. No change in TBARS levels was detected at any of the iron concentrations studied. Oxidative stress, measured by GSH kinetics over time, occurs when the RBC are incubated with colloidal iron hydroxide at concentrations higher than 10 µM of Fe3+. Overall, these results show that the intact human RBC is prone to oxidative stress when exposed to Fe3+ and that the RBC has a potent antioxidant system that can minimize the potential damage caused by acute exposure to a colloidal iron hydroxide in vitro.

Disfunção arterial como possível mecanismo de agressão cardíaca empacientes com Diabetes Mellitus tipo II: estudo doppler-ecocardiográfico / Arterial dysfunction as a possible mechanism od cardiac injury in type II Diabetic Patients: a doppler-echocardiography study

Objetivo - Avaliar a estrutura e função do ventrículo esquerdo (VE) e a rigidez arterial em portadores de diabetes mellitus tipo II. Métodos - Foram estudados 13 doentes diabéticos de ambos os sexox (55 "mais ou menos" 8 anos) sem outras doenças. A estrutura e funçäo do VE foram avaliadas por meio de ecodopplercardiografia associada à monitorizaçäo näo invasiva da pressäo arterial (PA). Os resultados foram comparados aos obtidos em grupo de indivíduos normais de mesma idade (n=12). Resultados - Näo houve diferenças entre os grupos quanto a PA diastólica, dimensöes das câmaras esquerdas e índices de funçäo sistólica e diastólica. Os pacientes diabéticos apresentaram índice de massa do VE (101 "mais ou menos" 10 vs 80 "mais ou menos" 14 g/m2; p "menor" 0,001) e índice de rigidez arterial sistêmica ( 0,86 "mais ou menos" 0,26 vs 0,69 "mais ou menos" 0,19 mmHg/mL; P "menor" 0,05) significantemente maiores que os controles. Conclusäo - O diabets mellitus está associado a aumento da rigidez arterial sistêmica e esse fator poderia contribuir para seus efeitos adversos sobre o VE.

Myocyte necrosis is the basis for fibrosis in renovascular hypertensive rats

The pathogenesis of fibrosis and the functional features of pressure overload myocardial hypertrophy are still controversial. The objectives of the present study were to evaluate the function and morphology of the hypertrophied myocardium in renovascular hypertensive (RHT) rats. Male Wistar rats were sacrificed at week 4 (RHT 4) and 8 (RHT8) after unilateral renal ischemia (Goldblatt II hypertension model). Normotensive rats were used as controls. Myocardial function was analyzed in isolated papillary muscle preparations, morphological features were defined by light microscopy, and myocardial hydroxyproline concentration (HOP) was determined by spectrophotometry. Renal artery clipping resulted in elevated systolic arterial pressure (RHT4: 178 + 19 mmHg and RHT8: 194 + 24 mmHg, P<0.05 vs control: 123 + 7 mmHg). Myocardial hypertrophy was observed in both renovascular hypertensive groups. The myocardial HOP concentration was increased in the RHT8 group (control: 2.93 + 0.38 mug/mg; RHT4: 3,02 + 0.40 mug/mg; RHT8: 3,44 + 0.45 mug/mg of dry tissue, P<0.05 vs control and RHT4 groups). The morphological study demonstrated myocyte necrosis, vascular damage and cellular inflammatory response throughout the experimental period. The increased cellularity was more intense in the adventitia of the arterioles. As a consequence of myocyte necrosis, there was an early, local conjunctive stroma collapse with disarray and thickening of the argyrophilic interstitial fibers, followed scarring. The functional data showed an increased passive myocardial stiffness in the RHT4 group. We conclude that renovascular hypertension induces myocyte and arteriole necrosis. Reparative fibrosis occurred as a consequence of the inflammatory response to necrosis. The mechanical behavior of the isolated papillary muscle was normal, except for an early increased myocardial passive stiffness.

Influence of diabetes mellitus on the glutathione redox system of human red blood cells

Several components of the erythrocyte-dependent glutathione redox system (reduced glutathione, GSH; oxidized glutathione, GSSG; glutathione peroxidase, GSH-Px; glutathione reductase, GSH-Red) were determined in patients with types I and II diabetes mellitus (DM). All groups studied were male subjects: G1, 200 young healthy individuals (aged 23.7 ñ 4.2 years); G2, 15 young insulin-treated type I DM patients; G3, 20 older older insulin-treated type II DM patiens; G4, 21 older oral hypoglycemic agent-treated type II DM patients; G5, 28 aged healthy individuals (aged 68.9 ñ 11.5 years). There were no differences between G1 and G3 or G4 regarding erythrocyte GSH, GSSG, and GSH-Red (without FAD) levels. GSH-Px activity was significantly lower in G2 when compared to G1 (15.2 ñ 4.9 vs 20.6 ñ 6.6 IU/g Hb). The GSH-Red and GSH-Px activities and GSH levels were significantly higher in G3 (4.6 ñ 1.7 IU/g Hb, 20.2 ñ 8.7 IU/g Hb and 3.5 ñ 1.3 uM/g Hb) and G4 (5.0 ñ 2.2 IU/g Hb, 16.9 ñ 6.1 IU/g Hb and 5.0 ñ 2.3 uM/g Hb) when compared to G5 (3.4 ñ 0.9 IU/g Hb, 12.0 ñ 3.6 IU/g Hb and 2.3 ñ 0.9 uM/g Hb). The findings suggest that treatment of DM can stimulate the redox activity of red blood cells in aged subjects

Age-related changes of glutathione content, glutathione reductase and glutathione peroxidase activity of human erythrocytes

In order to investigate the effect of aging on the erythrocyte glutathione system, total glutathione (GSH), glutathione reductase (GSH-red) and glutathione peroxidase (GSH-px) levels were measured in erythrocyte from 33 young (mean age=30.5ñ9.7 years) and 28 aged (mean age+68.9ñ11.4 years) healthy individuals. GSH was 3.5ñ1.8 *M/g Hb for the young group, a value significantly greater (P<0.01) than 2.3ñ0.9 *M/g Hb found for the aged group. Similary, GSH-red activity, 5.5ñ1.8 IU/g Hb, was higher (P,0.05) for the young group than 3.4ñ0.9 IU/g Hb found for the aged group. The GSH-px activity levels for the young group, 21.1ñ5.9 IU/g Hb, were significantly greater (P<0.01) than 12.0ñ3.3 IU/g Hb for the age group. The lower activity detected in the aged group for all of these parameters of the glutathione redox system was not related to low levels of hematocrit or hemoglobin. There was no statistical difference in the activation coefficient (AC) of reductase (+FAD/-FAD) between groups, which seems to indicate that the lower activity of glutathione reductase observed in the aged group was not due to riboflavin deficiency. Additional information is required to determine the mechanisms controlling the glutathione redox system and its role in the aging process

Estudo de hemoglobinopatia S em portadores de doenca de Chagas. / Hemoglobinopathy S in patients with Chagas' disease

Reacao de Machado-Guerreiro (MG) e eletroforesse de hemoglobina, para deteccao de hemoglobinopatia S, foram realizadas em amostras de sangue de 384 individuos residentes em Bambui (MG), regiao endemica de doenca de Chagas. Observou-se prevalencia de 73,9% de MG positivo e 3,l% de hemoglobinopatia S na amostra analisada. Nao se verificou nenhuma relacao entre presenca de hemoglobina S e reacao de Machado-Guerreiro, tampouco influencia do sexo nas prevalencias de Machado-Guerreiro e hemoglobinopatia S. A prevalencia de MachadoGuerreiro positivo foi maior nas faixas etarias mais avancadas e diminuiu acentuadamente na faixa mais jovem. Os autores sugerem que houve diminuicao da incidencia de doenca de Chagas na populacao, atribuida a melhoria das condicoes socio-economicas e vigilancia epidemiologica local, e que os portadores de hemoglobina S nao sao diferentemente susceptiveis a infestacao pelo Trypanosoma cruzi que a populacao normal

Malaria no municipio de Humaita, Estado do Amazonas. XIV - Inquerito coprologico em habitantes da regiao em relacao as taxas de hemoglobina. / Malaria in the municipality of Humaita, State of Amazonas. XIV - Coprological survey in inhabitants of the region in relation to hemoglobin levels

Em outubro de 1981, foram estudados 213 individuos do Municipio de Humaita, Estado do Amazonas, dos quais 91 eram habitantes de localidades situadas ao longo da calha do Rio Madeira e 122 do Bairro da Olaria, na zona urbana. Todos foram submetidos a inquerito clinico, epidemiologico e parasitologico de fezes pelas tecnicas de BAERMANN, FAUST & col. e HOFFMAN, PONS & JANER. De 65 habitantes da zona urbana e de 43 do Rio Madeira, foi feita determinacao da hemoglobina. De 25 habitantes da zona urbana e de 16 Rio Madeira, foi feita determinacao hemoglobina A2 pela cromatografia em microcoluna de D.E.A.E. celulose Os resultados revelaram que houve maior proporcao de infestacao parasitaria unica ou multipla entre os habitantes do Rio Madeira. Estes achados pode ser explicado pela diferenca das condicoes de higiene locais, pois, os habitantes do Rio Madeira nao dispoe de qualquer elemento de saneamento basico. Essas diferencas, contudo, nao influiram nos niveis de hemoglobina e de hemoglobina A2 que se mostraram semelhantes nos dois grupos

Malaria no municipio de Humaita, Estado do Amazonas. VIII - Comportamento das taxas de hemoglobina A2 em habitantes da regiao e em doentes. / Malaria en the municipality of Humaita, State of Amazonas VIII - Behavior of hemoglobin A2 level in inhabitants of the region and in patients

Em agosto de 1979 foram estudados 25 doentes com diagnostico confirmado de malaria e 45 individuos da populacao geral do Municipio de Humaita, Estado do Amazonas, 22 dos quais eram habitantes de localidades situadas ao longo do Rio Madeira, ll indios da tribo Tenhairim residentes no Km 126 da rodovia Transamazonica e, 12 do bairro da Olaria na zona urbana. Em todos eles foi determinado o nivel de hemoglobina A2 pela cromatografia em microcoluna de D.E.A.E. celulose. Os resultados observados revelaram o seguinte nivel de hemoglobina A2: 3,13% (mais ou menos 0,67%) entre os indios, 2,79% (mais ou menos 0,59%) nos habitantes do Rio Madeira; 2,18% (mais ou menos 0,44%) nos da zona urbana; e 3,06% (0,62%) nos doentes com malaria. A analise dos resultados mostrou que nao houve diferenca de comportamento do nivel de hemoglobina A2 na comparacao entre os doentes com malaria os habitantes do Rio Madeira e os indios. Os habitantes da zona urbana, entretanto, apresentaram nivel maior de hemoglobina A2. Esse fato poderia estar relacionado talvez, a um mais baixo padrao de vida e maior infestacao parasitaria dos habitantes do bairro da Olaria, que estariam acarretando deficiencia de ferro, com consequente menor sintese de hemoglobina A2