Metalloproteinases-2 and -9 predict left ventricular remodeling after myocardial infarction

Background: The role of serum metalloproteinases (MMP) after myocardial infarction (MI) is unknown. Objective: The aim of this study was to evaluate the role of serum MMP-2 and -9 as predictors of ventricular remodeling six months after anterior MI. Methods: We prospectively enrolled patients after their first anterior MI. MMP activity was assayed 12 to 72 hours after the MI. An echocardiogram was performed during the hospitalization and six months later. Results: We included 29 patients; 62% exhibited ventricular remodeling. The patients who exhibited remodeling had higher infarct size based on creatine phosphokinase (CPK) peak values (p = 0.037), higher prevalence of in-hospital congestive heart failure (p = 0.004), and decreased ejection fraction (EF) (p = 0.007). The patients with ventricular remodeling had significantly lower serum levels of inactive MMP-9 (p = 0.007) and significantly higher levels of the active form of MMP-2 (p = 0.011). In a multivariate logistic regression model, adjusted by age, CPK peak, EF and prevalence of heart failure, MMP-2 and -9 serum levels remained associated with remodeling (p = 0.033 and 0.044, respectively). Conclusion: Higher serum levels of inactive MMP-9 were associated with the preservation of left ventricular volumes, and higher serum levels of the active form of MMP-2 were a predictor of remodeling 6 months after MI. (Arq Bras Cardiol. 2013;100(4):315-321).

Mechanical, biochemical, and morphological changes in the heart from chronic food-restricted rats

Food restriction (FR) has been shown to induce important morphological changes in rat myocardium. However, its influence on myocardial performance is not completely defined. We examined the effects of chronic FR on cardiac muscle function and morphology. Sixty-day-old Wistar-Kyoto rats were fed a control (C) or a restricted diet (daily intake reduced to 50% of the amount of food consumed by the control group) for 90 days. Myocardial performance was studied in isolated left ventricular (LV) papillary muscle. Fragments of the LV free wall were analysed by light microscopy, and the ultrastructure of the myocardium was examined in the LV papillary muscle. The myocardial collagen concentration was also evaluated. FR decreased body weight (BW) and LV weight (LVW); the LVW/BW ratio was higher in the restricted group (C, 1.86 +/- 0.17 mg/g; FR, 2.19 +/- 0.31 mg/g; p < 0.01). In the FR animals, the cardiac fibers were polymorphic, some of them were of small diameter and others presented lateral infoldings; the ultrastructural alterations were focal and included reduction of sarcoplasmic content, absence and (or) disorganization of myofilaments and Z line, numerous electron dense and polymorphic mitochondria, and deep infoldings of the plasma membrane. The hydroxyproline concentration was higher in the FR animals (p < 0.01). FR prolonged the contraction and relaxation time of the papillary muscle and did not change its ability to contract and shorten. In conclusion, although a 90-day period of FR caused striking myocardial ultrastructural alterations and increased the collagen concentration, it only minimally affected the mechanical function.

O bloqueio do sistema renina-angiotensina atenua a remodelação cardíaca de ratos submetidos a estenose aórtica

OBJETIVO: Avaliar o papel do bloqueador dos receptores AT1 e do inibidor da enzima conversora da angiotensina na remodelação cardíaca induzida por estenose aórtica em ratos. MÉTODOS: Ratos Wistar foram divididos em 4 grupos: controle (C, n=13), estenose aórtica (EAo, n=11), EAo com lisinopril, 20 mg/kg/dia (LIS, n=11) e EAo com losartan, 40 mg/kg/dia (LOS, n=9). Os tratamentos foram iniciados 3 dias antes da cirurgia. Após 6 semanas, os animais foram submetidos ao estudo ecocardiográfico, quantificação da concentração de hidroxiprolina e da área seccional (CSA) miocitária do ventrículo esquerdo (VE). RESULTADOS: A EAo induziu aumento da espessura da parede do VE. Os animais LIS e LOS não apresentaram diferença em relação aos animais controles. Os ratos EAo e LIS apresentaram maiores diâmetros do átrio esquerdo que os ratos controles, enquanto nos animais LOS não houve diferença. Os animais com EAo apresentaram maiores valores da porcentagem de encurtamento que os controle. Esse fato não foi modificado com LIS ou LOS. A CSA dos animais do grupo EAo foi maior que a dos controle. Entretanto, o tratamento com LOS e com LIS atenuou o aumento da área induzida pela EAo. A EAo resultou em aumento na concentração de HOP, enquanto o grupo LOS não apresentou diferença em relação ao grupo controle. CONCLUSÃO: O bloqueio do sistema renina-angiotensina, com bloqueador AT1 e com IECA, pode atenuar o desenvolvimento de hipertrofia cardíaca, porém só o bloqueio dos receptores AT1 atenua a fibrose intersticial do VE.

Combined exercise training in asymptomatic elderly with controlled hypertension: Effects on functional capacity and cardiac diastolic function

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Heart Failure After Myocardial Infarction: Clinical Implications and Treatment

Heart failure is a frequent complication of myocardial infarction. Several factors, such as recurrent myocardial ischemia, infarct size, ventricular remodeling, stunned myocardium, mechanical complications, and hibernating myocardium influence the appearance of left ventricular systolic dysfunction after myocardial infarction. Importantly, its presence increases the risk of death by at least 3- to 4-fold. The knowledge of the mechanisms and clinical features are essential for the diagnosis and treatment of left ventricular dysfunction and heart failure after myocardial infarction. Therefore, this review will focus on the clinical implications and treatment of heart failure after myocardial infarction.

Effect of lycopene on doxorubicin-induced cardiotoxicity: An echocardiographic, histological and morphometrical assessment

Doxorubicin is an excellent chemotherapeutic agent utilized for several types of cancer but the irreversible doxorubicin-induced cardiac damage is the major limitation for its use. Oxidative stress seems to be associated with some phase of the toxicity mechanism process. To determine if lycopene protects against doxorubicin-induced cardiotoxicity, male Wistar rats were randomly assigned either to control, lycopene, doxorubicin or doxorubicin + lycopene groups. They received corn oil (control, doxorubicin) or lycopene (5 mg/kg body weight a day) (lycopene, doxorubicin + lycopene) by gavage for a 7-week period. They also received saline (control, lycopene) or doxorubicin (4 mg/kg) (doxorubicin, doxorubin + lycopene) intraperitoneally by week 3, 4 5 and 6. Animals underwent echocardiogram and were killed for tissue analyses by week 7. Mean lycopene levels (nmol/kg) in liver were higher in the doxorubicin + lycopene group (5822.59) than in the lycopene group (2496.73), but no differences in lycopene were found in heart or Plasma of these two groups. Lycopene did not prevent left ventricular systolic dysfunction induced by doxorubicin. However, morphologic examination revealed that doxorubicin-induced myocyte damage was significantly suppressed in rats treated with lycopene. Doxorubicin treatment was followed by increase of myocardium interstitial collagen volume fraction. Our results show that: (i) doxorubicin-induced cardiotoxicity was confirmed by echocardiogram and morphological evaluations; (ii) lycopene absorption was confirmed by its levels in heart, liver and plasma; (iii) lycopene supplementation provided myocyte protection without preventing interstitial collagen accumulation increase; (iv) doxorubicin-induced cardiac dysfunction was not prevented by lycopene supplementation; and (v) lycopene depletion was not observed in plasma and tissues from animals treated with doxorubicin.

Growth hormone attenuates skeletal muscle changes in experimental chronic heart failure

Objective: This study evaluated the effects of growth hormone (GH) on morphology and myogenic regulatory factors (MRF) gene expression in skeletal muscle of rats with ascending aortic stenosis (AAS) induced chronic heart failure.Design: Male 90-100 g Wistar rats were subjected to thoracotomy. AAS was created by placing a stainless-steel clip on the ascending aorta. Twenty five weeks after surgery, rats were treated with daily subcutaneous injections of recombinant human GH (2 mg/kg/day; AAS-GH group) or saline (AAS group) for 14 days. Sham-operated animals served as controls. Left ventricular (LV) function was assessed before and after treatment. IGF-1 serum levels were measured by ELISA. After anesthesia, soleus muscle was frozen in liquid nitrogen. Histological sections were stained with HE and picrosirius red to calculate muscle fiber cross-sectional area and collagen fractional area, respectively. MRF myogenin and MyoD expression was analyzed by reverse transcription PCR.Results: Body weight was similar between groups. AAS and AAS-GH groups presented dilated left atrium, left ventricular (LV) hypertrophy (LV mass index: Control 1.90 +/- 0.15; AAS 3.11 +/- 0.44; AAS-GH 2.94 +/- 0.47 g/kg; p < 0.05 AAS and AAS-GH vs. Control), and reduced LV posterior wall shortening velocity. Soleus muscle fiber area was significantly lower in AAS than in Control and AAS-GH groups; there was no difference between AAS-GH and Control groups. Collagen fractional area was significantly higher in MS than Control; AAS-GH did not differ from both Control and AAS groups. Serum IGF-1 levels decreased in AAS compared to Control. MyoD mRNA was significantly higher in AAS-GH than AAS; there was no difference between AAS-GH and Control groups. Myogenin mRNA levels were similar between groups.Conclusion: In rats with aortic stenosis-induced heart failure, growth hormone administration increases MyoD gene expression above non-treated animal levels, preserves muscular trophism and attenuates interstitial fibrosis. These results suggest that growth hormone may have a potential role as an adjuvant therapy for chronic heart failure. (C) 2009 Elsevier Ltd. All rights reserved.

Papel relativo da remodelação geométrica do ventrículo esquerdo, morfológica e funcional do miocárdio na transição da hipertrofia compensada para a falência cardíaca em ratos com estenose aórtica supravalvar

OBJETIVO: Avaliar a contribuição relativa da remodelação geométrica do ventrículo esquerdo (VE) e das alterações morfológicas e funcionais do miocárdio, em ratos com estenose aórtica supravalvar (EAS), na fase de transição da hipertrofia compensada para a insuficiência cardíaca congestiva (ICC). MÉTODOS: Vinte e uma semanas após a indução da EAS os ratos foram classificados como controles (GC,n=13), não portadores (GE,n=11) ou portadores de insuficiência cardíaca congestiva (GE-IC,n=12).Todos os grupos foram avaliados com estudo ecocardiográfico, hemodinâmico e morfológico do miocárdio. RESULTADOS: Vinte e uma semanas após EAS: índice de massa (GE-IC>GE>GC,p<0.05); pressão sistólica: (GE-IC = GE>GC, p<0,05); pressão diastólica: (GE-IC>GE>GC, p<0,05); estresse meridional sistólico e diastólico: (GE-IC>GE>GC,p<0.05); área de secção dos miócitos: (GE-IC>GE>GC, p<0,05) e conteúdo de hidroxiprolina: (GE-IC>GE>GC, p<0,05) do VE. No grupo GE-IC o remodelamento geométrico do VE foi caracterizado por aumento significante das dimensões e espessura relativa da parede normal (remodelamento excêntrico) enquanto que o grupo GE apresentou remodelamento concêntrico. Os índices de desempenho do VE do grupo GE-IC foram significantemente menores que do grupo GE. CONCLUSÃO: Os grupos GE-IC e GE diferiram primariamente no processo de remodelação geométrica do VE e estrutural do miocárdio que estabeleceu um estado cronicamente compensado no grupo GE e precipitou a ICC no grupo GE-IC na vigência de graus equivalentes de comprometimento da contratilidade. Neste modelo experimental a fase de transição da hipertrofia compensada para a ICC está mais estreitamente relacionada com o remodelamento geométrico adverso do VE e estrutural do miocárdio do que com o grau de comprometimento da contratilidade.

PROTECTIVE EFFECTS OF DILTIAZEM ON THE MECHANICAL PERFORMANCE OF THE HYPOXIC MYOCARDIUM

1. To determine whether diltiazem protects the hypoxic myocardium by reducing contractile work, we have compared the effects of diltiazem and quiescence on left ventricular (LV) papillary muscle subjected to hypoxia. Papillary muscles were obtained from male Charles River CD rats weighing 150-250 g.2. Four groups of muscles were studied: control (N = 6), non-stimulation (N = 10), diltiazem 10(-4) M (N = 6) and diltiazem 10(-4) M plus non-stimulation (N = 10).3. Isolated mt LV papillary muscles were studied in Krebs-Henseleit solution with a calcium concentration of 2.52 mM at 28-degrees-C while contracting isometrically at a stimulation rate of 0.2 Hz. Resting tension and active isometric tension were measured.4. Both diltiazem and quiescence significantly attenuated contracture tension during hypoxia (0.91 +/- 0.10 vs 2.26 +/- 0.49 g/mm2 for diltiazem vs control, and 0.55 +/- 0.18 vs 2.26 +/- 0.49 g/mm2 for quiescence vs control). Recovery of active tension was improved in the diltiazem groups during reoxygenation (4.16 +/- 0.42 vs 3.75 +/- 0.51, 3.53 +/- 0.15 vs 2.90 +/- 0.13, 5.84 +/- 0.33 vs 6.48 +/- 0.29 and 5.98 +/- 0.90 vs 7.67 +/- 0.68 g/mm2 for diltiazem, diltiazem non-stimulation, non-stimulation and control groups).5. The results suggest that the protective effect of diltiazem during hypoxia was due to the reduction in energy demand of the myocardium.

Relações pressão-diâmetro e esforço-diâmetro do ventrículo esquerdo em seres humanos. Padronização e análise crítica do método.

PURPOSE--To provide a critical analysis of the fluid filled manometric system and M-mode echocardiography and, by their association, to standardize the determination of left ventricular (LV) pressure-diameter and stress-diameter relationships in humans. MATERIAL AND METHODS--The pressure curve and the LV M-mode image was obtained in 24 patients with cardiopathy. The dynamic characteristics of the fluid-filled system have been studied to define the amplitude, the resonance and the time gap of the pressure curve register. The delay of the pressure curve recording was determined in all cases by comparing pressure curve and echocardiographic aortic valve registers. The values of pressure, diameter, posterior wall thickness and LV meridional stress was calculated at every 0.02s. RESULTS--Preliminary analyses of the fluid-filled manometric system indicated that this system has variable dynamic characteristics. The pressure-diameter and stress-diameter loops obtained were similar to those of the literature. The values of end-systolic stress, percentage of fractional shortening, ejection fraction and circumferential fiber shortening rate of patients with dilated cardiomyopathy (n = 5) were significantly reduced when compared to the values of patients without left ventricular overload (n = 8) and patients with ventricular volume overload. It has been verified, also, that the retard of the pressure curve record introduced by the fluid-filled manometric system does not modify the values of these variables. CONCLUSION--The LV pressure-diameter and stress-diameter relationships obtained by the association of echocardiography and LV manometry showed functional characteristics of the ventricle that could not appear by the use of the echocardiography or by the LV manometry themselves.

Doppler echocardiography in athletes from different sports

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Influência do diabetes mellitus no coração de ratos senescentes espontaneamente hipertensos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeito do bloqueio da aldosterona na remodelação cardíaca de ratos espontaneamente hipertensos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Influência da inibição da NADPH oxidase sobre o redemodelamento cardíaco de ratos com diabetes mellitus

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Influência do exercício físico sobre a remodelaçao cardíaca e a atividade oxidativa em ratos diabéticos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)