Obesity induces upregulation of genes involved in myocardial Ca2+ handling

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Influence of educational level on myocardial hypertrophy of hemodialysis patients

Introduction: Chronic renal disease is associated with a high cardiovascular risk. Data from the general population associate cardiovascular diseases with low educational level, but no study has evaluated this association in patients on hemodialysis. Objective: This study aimed at evaluating the association between educational level, hypertension, and left ventricular hypertrophy in patients on chronic hemodialysis. Methods: A standard socioeconomic questionnaire was applied to 79 hemodialysis patients at the Hospital das Clínicas of Faculdade de Medicina de Botucatu, state of São Paulo. Clinical, laboratory and echocardiographic data were obtained from medical records. The patients were divided into two groups according to the median educational level, as follows: G1, patients with three or less years of schooling; G2, patients with more than three years of schooling. Results: Blood pressure, interdialytic weight gain, and variables statistically different in the two groups (p < 0.2) underwent multiple analysis. Independent associations were stated with p < 0.05 in multiple analysis. The mean age of patients was 57 ± 12.8 years, 46 were males (57%), and 53 white (67%). The variables selected for multiple analysis were: age (p = 0.004); educational level (p < 0.0001); body mass index (p = 0.124); left ventricular diameter (p = 0.048); and left ventricular mass index (p = 0.006). Antihypertensive drugs were similar in both groups. Systolic blood pressure (p = 0.006) and years of schooling (p = 0.047) had a significant and independent correlation with left ventricular mass index. Conclusion: In hemodialysis patients, left ventricular mass associated not only with blood pressure but also with educational level.

Comparative study between trimetazidine and ice slush hypothermia in protection against renal ischemia/reperfusion injury in a porcine model

Purpose: The aim of the study was to compare the effects of renal ice slush hypothermia and the use of trimetazidine in the protection against ischemia/reperfusion (I/R) injury.Materials and Methods: Fifteen farm pigs were submitted to left kidney ischemia and right nephrectomy during the same procedure. Animals were divided into three groups. Group 1 was submitted to warm ischemia; Group 2 was submitted to cold ischemia with ice slush; and Group 3 received trimetazidine 20 mg one day and 4 hours before surgery. Ischemia time was 120 minutes in all three groups. Serum creatinine (SCr) and plasma iohexol clearance (CLioh) were measured before surgery and on postoperative days (PODs) 1,3,7, and 14. Semi-quantitative analyses of histological alterations were performed by a pathologist. A p value of < 0.05 was considered significant.Results: All groups showed elevation of serum creatinine in the first week. Serum creatinine was higher in Group 3 in the first and third postoperative days (Mean Cr: 5.5 and 8.1 respectively). Group 2 showed a lower increase in creatinine and a lower decrease in iohexol clearance than the others. Renal function stabilized in the fourteenth POD in all three groups. Analyses of histological alterations did not reach statistical significance between groups.Conclusion: Trimetazidine did not show protection against renal I/R injury in comparison to warm ischemia or hypothermia in a porcine model submitted to 120 minutes of renal ischemia.

Systemic evaluation on ischemia and reperfusion injury of splanchnic organs in rats

OBJETIVO: Avaliar as alterações hemodinâmicas e sistêmicas decorrentes de isquemia e reperfusão (I/R) esplâncnica em ratos. MÉTODOS: Vinte ratos foram divididos em dois grupos: grupo controle: os animais foram submetidos à cirurgia, mas não a I/R e foram tratados com solução fisiológica (5 ml/kg/h) por 150 minutos; grupo I/R: os animais foram submetidos à administração contínua de solução fisiológica e à oclusão do tronco celíaco, artéria mesentérica superior e artéria mesentérica inferior por 30 minutos, seguidos por 120 minutos de reperfusão. Avaliou-se a pressão arterial média, pressão venosa, fluxo sangüíneo na aorta e na artéria mesentérica superior, freqüência cardíaca, temperatura esofágica e hematócrito. RESULTADOS: Durante a reperfusão, no grupo I/R, houve uma diminuição progressiva da pressão arterial média, fluxo sangüíneo na aorta e artéria mesentérica superior, freqüência cardíaca e temperatura esofágica; pressão venosa e hematócrito não sofreram alteração. CONCLUSÃO: O modelo de isquemia provocado por oclusão da artéria mesentérica superior, artéria mesentérica inferior e tronco celíaco por 30 minutos seguidos por 120 minutos de reperfusão provoca alterações sistêmicas evidenciadas por hipotensão, diminuição do fluxo sangüíneo mesentérico, da freqüência cardíaca e da temperatura esofágica.

Myocardial dysfunction induced by food restriction is related to morphological damage in normotensive middle-aged rats

Previous works from our laboratory have revealed that food restriction (FR) promotes discrete myocardial dysfunction in young rats. We examined the effects of FR on cardiac function, in vivo and in vitro, and ultrastructural changes in the heart of middle-aged rats. Twelve-month-old Wistar- Kyoto rats were fed a control (C) or restricted diet (daily intake reduced to 50% of the control group) for 90 days. Cardiac performance was studied by echocardiogram and in isolated left ventricular (LV) papillary muscle by isometric contraction in basal condition, after calcium chloride (5.2 mM) and beta- adrenergic stimulation with isoproterenol (10(-6) M). FR did not change left ventricular function, but increased time to peak tension, and decreased maximum rate of papillary muscle tension development. Inotropic maneuvers promoted similar effects in both groups. Ultrastructural alterations were seen in most FR rat muscle fibers and included, absence and/or disorganization of myofilaments and Z line, hyper-contracted myofibrils, polymorphic and swollen mitochondria with disorganized cristae, and a great quantity of collagen fibrils. In conclusion, cardiac muscle sensitivity to isoproterenol and elevation of extracellular calcium concentration is preserved in middle-aged FR rats. The intrinsic muscle performance depression might be related to morphological damage.

Exercise training increases myocardial inotropic response in food restricted rats

This study evaluated the effects of exercise training on myocardial function and ultrastructure of rats submitted to different levels of food restriction (FR). Male Wistar-Kyoto rats, 60 days old, were submitted to free access to food, light FR (20%), severe FR (50%) and/or to swimming training (one hour per day with 5% of load, five days per week for 90 days). Myocardial function was evaluated by left ventricular papillary muscle under basal condition (calcium 1.25 mM), and after extracellular calcium elevation to 5.2 mM and isoproterenol (I PM) addition. The ultrastructure of the myocardium was examined in the papillary muscle. The training effectiveness was verified by improvement of myocardial metabolic enzyme activities. Both 20% and 50% food restriction protocols presented minor body and ventricular weights gain. The 20%-FR, in sedentary or trained rats, did not alter myocardial function or ultrastructure. The 50%-FR, in sedentary rats, caused myocardial dysfunction under basal condition, decreased response to inotropic stimulation, and promoted myocardial ultrastructural damage. The 50%-FR, in exercised rats, increased myocardial dysfunction under basal condition but increased response to inotropic stimulation although there was myocardial ultrastructural damage. In conclusion, the exercise training in severe restriction caused marked myocardial dysfunction at basal condition but increased myocardial response to inotropic stimulation. (c) 2005 Elsevier B.V.. All rights reserved.

Myocardial dysfunction induced by food restriction is related to calcium cycling and beta-adrenergic system changes

Food restriction (FR) has been shown to promote myocardial dysfunction in rats. The aim of this study was to verify the participation of calcium and beta-adrenergic system on myocardial mechanical alteration in rats submitted to FR. Myocardial performance was studied in isolated left ventricular papillar muscle from young Wistar-Kyoto rats (WKY) submitted to FR or to control diet. The groups subjected to FR were fed 50% less food than the control group for 90 days. Mechanical function was studied in isometric contraction at post-rest contraction of 30 seconds (PRC), calcium chloride concentration 5.20 mM, and beta-adrenergic stimulation with isoproterenol 10(-6) M. FR decreased the body weight, and left and right ventricular weight. In basal condition (1.25 MM of calcium) time to peak tension (TPT) and time from peak tension to 50% relaxation (RT50) were greater in the FR group. Muscle function was. The same in both PRC groups. TPT decrease in both high calcium groups, more in FR rats; RT50 dropped only in FR animals. TPT decreased in both Isoproterenol groups, more intensely in the FR group. This result suggests that food restriction impairs myocardial performance and these changes may be attributed to alterations in the intracellular calcium cycling and beta-adrenergic system. (C) 2003 Elsevier B.V. All rights reserved.

Food restriction impairs myocardial inotropic response to calcium and beta-adrenergic stimulation in spontaneously hypertensive rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

GROWTH HORMONE ATTENUATES MYOCARDIAL FIBROSIS IN RATS WITH CHRONIC PRESSURE OVERLOAD-INDUCED LEFT VENTRICULAR HYPERTROPHY

1. The role of growth hormone (GH) in cardiac remodelling and function in chronic and persistent pressure overload-induced left ventricular hypertrophy has not been defined. The aim of the present study was to assess short-term GH treatment on left ventricular function and remodelling in rats with chronic pressure overload-induced hypertrophy.2. Twenty-six weeks after induction of ascending aortic stenosis (AAS), rats were treated with daily subcutaneous injections of recombinant human GH (1 mg/kg per day; AAS-GH group) or saline (AAS-P group) for 14 days. Sham-operated animals served as controls. Left ventricular function was assessed by echocardiography before and after GH treatment. Myocardial fibrosis was evaluated by histological analysis.3. Before GH treatment, AAS rats presented similar left ventricular function and structure. Treatment of rats with GH after the AAS procedure did not change bodyweight or heart weight, both of which were higher in the AAS groups than in the controls. After GH treatment, posterior wall shortening velocity (PWSV) was lower in the AAS-P group than in the control group. However, in the AAS-GH group, PWSV was between that in the control and AAS-P groups and did not differ significantly from either group. Fractional collagen (% of total area) was significantly higher in the AAS-P and AAS-GH groups compared with control (10.34 +/- 1.29, 4.44 +/- 1.37 and 1.88 +/- 0.88%, respectively; P < 0.05) and was higher still in the AAS-P group compared with the AAS-GH group.4. The present study has shown that short-term administration of GH to rats with chronic pressure overload-induced left ventricular hypertrophy induces cardioprotection by attenuating myocardial fibrosis.

Severe food restriction induces myocardial dysfunction related to SERCA2 activity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Tissue Vitamin A Insufficiency Results in Adverse Ventricular Remodeling after Experimental Myocardial Infarction

Background/Aims: The role of tissue vitamin-A insufficiency on post-infarction ventricular remodeling is unknown. We tested the hypothesis that cardiac vitamin A insufficiency on post-infarction is associated with adverse myocardial remodeling. Methods: After infarction, rats were allocated into two groups: C (controls, n=25); VA (dietary vitamin A restriction, n= 26). After 3 months, the animals were submitted to echocardiogram, morphometric and biochemical analysis. Results: Rats fed the vitamin-A-deficient diet had lower heart and liver retinol concentration and normal plasma retinol. There were no differences in infarct size between the groups. VA showed higher diastolic left ventricular area normalised by body weight (C= 1.81 +/- 0.4 cm2/kg, VA= 2.15 +/- 0.3 cm2/kg; p=0.03), left ventricular diameter (C= 9.4 +/- 1.4 mm, VA= 10.5 +/- 1.2 mm; p=0.04), but similar systolic ventricular fractional area change (C= 33.0 +/- 10.0 %, VA= 32.1 +/- 8.7 %; p=0.82). VA showed decreased isovolumetric relaxation time normalised by heart rate (C= 68.8 +/- 11.4 ms, VA= 56.3 +/- 16.8 ms; p=0.04). VA showed higher interstitial collagen fraction (C= 2.8 +/- 0.9 %, VA= 3.7 +/- 1.1 %; p=0.05). There were no differences in myosin heavy chain expression, metalloproteinase 2 and 9 activation, or IFN-gamma and TNF-alpha cardiac levels. Conclusion: Local tissue vitamin A insufficiency intensified ventricular remodeling after MI, worsening diastolic dysfunction. Copyright (C) 2010 S. Karger AG, Basel

Influence of AIN-93 diet on mortality and cardiac remodeling after myocardial infarction in rats

Background: The AIN-93 diet was proposed by the American Institute of Nutrition with the objective of standardising studies in experimental nutrition. Our objective was to analyze the effects of AIN-93 diet after myocardial infarction in rats.Methods: Post weaning, the animals were divided into two groups: control (C, n=62), fed the standard diet of our laboratory (Labina); AIN-93 Group (n=70), fed the AIN-93 diet. Achieving 250 g, the animals were subjected to myocardial infarction.Results: Early mortality was increased in AIN-93 animals, associated with lower serum levels of calcium, magnesium, potassium, sodium, and phosphorus. on the other hand, after 90 days, AIN-93 showed smaller normalized left ventricular dimensions. The caloric and carbohydrate intake was smaller, but the fat intake was higher in AIN-93 rats. AIN-93 group also showed increased levels of beta-hydroxyacylcoenzyme A dehydrogenase and citrate synthase. In addition, serum levels of insulin and cardiac levels of malondialdehyde, metalloproteinases-2 and -9, and TNF-alpha and IFN-gamma were decreased in the AIN-93 group.Conclusion: AIN-93 diet increased early mortality, while attenuated the chronic remodeling process after experimental coronary occlusion. Therefore, this diet has biological effects and should be use with attention in this model. (C) 2010 Elsevier B.V. All rights reserved.