Ventricular systolic reserve in asymptomatic children previously treated with low doses of anthracyclines: A longitudinal, prospective exercise echocardiography study

Background: The time course of mild cardiotoxicity induced by anthracycline remains unknown. The aim of this study was to evaluate the long-term evolution of decreased myocardial reserve in children previously treated with a cumulative dose of anthracycline up to 100mg/m 2. Patients and Methods: Twenty-seven asymptomatic cancer survival patients (25 with lymphoblastic leukemia), in continuous remission and off treatment for >12 months with no alterations in conventional echocardiograms were evaluated by exercise echocardiography at 37±15.4 months (T1) and 101±24 months (T2) after finishing treatment (ADRIA group). This group was compared with 25 healthy individuals (control group) similar to the ADRIA group with respect to age and body surface area (BSA). All individuals underwent treadmill exercise testing according to Bruce protocol. Echocardiograms were performed before and immediately after exercise. Results: The groups were similar regarding cardiac structure and left ventricular (LV) systolic function at rest at T1 and T2. The growth of LV posterior wall thickness related to BSA was lower in the ADRIA group at T2. Post exercise, smaller LV ejection indexes and attenuated changes in the afterload in ADRIA group were observed at T1 and T2. Conclusion: The decreased systolic reserve induced by a low dose of anthracycline in asymptomatic children and adolescents remains unaffected over a 5-year period, suggesting that positive outcomes in chronic cardiotoxicity would be expected in patients with mild impairment after anthracycline treatment. © 2011 Wiley Periodicals, Inc.

Cardiac remodeling induced by smoking: Concepts, relevance, and potential mechanisms

Cardiac or ventricular remodeling is characterized by molecular, cellular, and interstitial alterations that lead to changes in heart size, mass, geometry and function in response to a given insult. Currently, tobacco smoke exposure is recognized as one of these insults. Indeed, tobacco smoke exposure induces the enlargement of the left-sided cardiac chambers, myocardial hypertrophy, and ventricular dysfunction. Potential mechanisms for these alterations include hemodynamic and neurohormonal changes, oxidative stress, inflammation, nitric oxide bioavailability, matrix metalloproteinases and mitogen-activated protein kinase activation. This review will focus on the concepts, relevance, and potential mechanisms of cardiac remodeling induced by tobacco smoke. © 2012 Bentham Science Publishers.

Waist circumference, but not body mass index, is a predictor of ventricular remodeling after anterior myocardial infarction

Objective: The impact of obesity on ventricular remodeling after myocardial infarction (MI) is still poorly understood. Therefore, the aim of this study was to evaluate the role of waist circumference (WC) and body mass index as predictors of cardiac remodeling in patients after an anterior MI. Methods: Eighty-three consecutive patients with anterior MI were prospectively evaluated. Clinical characteristics and echocardiographic data were analyzed at admission and at a 6-mo follow-up. Ventricular remodeling was defined as a 10% increase in left ventricular end-systolic or end-diastolic diameter at the 6-mo follow-up. Results: In our study, 83 consecutive patients were evaluated (72% men). Ventricular remodeling was present in 31% of the patients (77% men). Patients with remodeling had higher creatine phosphokinase and creatine phosphokinase-MB peak values, a higher resting heart rate, a larger left atrial diameter, and a larger interventricular septum diastolic thickness. In addition, patients with remodeling had lower peak velocity of early ventricular filling deceleration time and ejection fraction. Patients with remodeling presented higher WC values (with remodeling, 99.2 ± 10.4 cm; without remodeling, 93.9 ± 10.8 cm, P = 0.04), but there were no differences in the body mass index values. In the logistic regression analysis, WC, adjusted by age, gender, ejection fraction, and creatine phosphokinase levels, was an independent predictor of left ventricular remodeling (odds ratio 1.067, 95% confidence interval 1.001-1.129, P = 0.02). Conclusion: Waist circumference, but not body mass index, is a predictor of ventricular remodeling after an anterior MI. Therefore, the WC of these patients should be measured in clinical practice. © 2013 Elsevier Inc.

Infliximab prevents increased systolic blood pressure and upregulates the AKT/eNOS pathway in the aorta of spontaneously hypertensive rats

High systolic blood pressure caused by endothelial dysfunction is a comorbidity of metabolic syndrome that is mediated by local inflammatory signals. Insulin-induced vasorelaxation due to endothelial nitric oxide synthase (eNOS) activation is highly dependent on the activation of the upstream insulin-stimulated serine/threonine kinase (AKT) and is severely impaired in obese, hypertensive rodents and humans. Neutralisation of circulating tumor necrosis factor-α (TNFα) with infliximab improves glucose homeostasis, but the consequences of this pharmacological strategy on systolic blood pressure and eNOS activation are unknown. To address this issue, we assessed the temporal changes in the systolic pressure of spontaneously hypertensive rats (SHR) treated with infliximab. We also assessed the activation of critical proteins that mediate insulin activity and TNFα-mediated insulin resistance in the aorta and cardiac left ventricle. Our data demonstrate that infliximab prevents the upregulation of both systolic pressure and left ventricle hypertrophy in SHR. These effects paralleled an increase in AKT/eNOS phosphorylation and a reduction in the phosphorylation of inhibitor of nuclear factor-κB (Iκβ) and c-Jun N-terminal kinase (JNK) in the aorta. Overall, our study revealed the cardiovascular benefits of infliximab in SHR. In addition, the present findings further suggested that the reduction of systolic pressure and left ventricle hypertrophy by infliximab are secondary effects to the reduction of endothelial inflammation and the recovery of AKT/eNOS pathway activation. © 2012 Elsevier B.V.

Cardiac remodeling induced by 13-cis retinoic acid treatment in acne patients

Background: Currently, 13-cis-retinoic acid (13-cis-RA) is the most effective therapy for acne. Isotretinoin, a first-generation synthetic 13-cis-RA compound, is associated with numerous adverse effects. To investigate the cardiac effects of 13-cis-RA, acne patients receiving 13-cis-RA were studied. Methods: Twenty male patients with acne were enrolled in the study. Patients were treated with a dose of 0.5 mg/kg/d of isotretinoin. All participants were assessed prior to treatment and after 10 weeks of therapy with Doppler-echocardiogram. Results: Patients showed reductions in right atrium vertical diameter, left atrium longitudinal diameter, left atrium volume and left ventricular diastolic diameter over the course of treatment. Significant increases in interventricular septum diastolic thickness, posterior wall diastolic thickness, relative wall relative thickness and left ventricle (LV) mass were observed. The LV mass index showed an increase in ventricular mass and a decrease in the cavity size. Examining LV systolic function, a decrease was observed for the cardiac index. Conclusion: In this study, 10 weeks of 13-cis-RA therapy at a dose of 0.5 mg/kg/d was found to promote concentric-type heart remodeling due to the occurrence of two associated events: heart hypertrophy and hypovolemia. © 2011 Elsevier B.V. All rights reserved.

Mechanisms Involved in the Beneficial Effects of Spironolactone after Myocardial Infarction

Introduction:Our objective was to analyze the effect of spironolactone on cardiac remodeling after experimental myocardial infarction (MI), assessed by matricellular proteins levels, cardiac collagen amount and distribution, myocardial tissue metalloproteinase inhibitor-1(TIMP-1) concentration, myocyte hypertrophy, left ventricular architecture, and in vitro and in vivo cardiac function.Methods:Wistar rats were assigned to 4 groups: control group, in which animals were submitted to simulated surgery (SHAM group; n=9); group that received spironolactone and in which animals were submitted to simulated surgery (SHAM-S group, n=9); myocardial infarction group, in which animals were submitted to coronary artery ligation (MI group, n=15); and myocardial infarction group with spironolactone supplementation (MI-S group, n=15). The rats were observed for 3 months.Results:The MI group had higher values of left cardiac chambers and mass index and lower relative wall thicknesses compared with the SHAM group. In addition, diastolic and systolic functions were worse in the MI groups. However, spironolactone did not influence any of these variables. The MI-S group had a lower myocardial hydroxyproline concentration and myocyte cross-sectional area compared with the MI group. Myocardial periostin and collagen type III were lower in the MI-S group compared with the MI-group. In addition, TIMP-1 concentration in myocardium was higher in the MI-S group compared with the MI group.Conclusions:The predominant consequence of spironolactone supplementation after MI is related to reductions in collagens, with discrete attenuation of other remodeling variables. Importantly, this effect may be modulated by periostin and TIMP-1 levels. © 2013 Minicucci et al.

Histoquímica e ultra-estrutura da musculatura ventricular esquerda de ratos diabéticos: efeitos do exercício físico

Pós-graduação em Ciências Biológicas (Biologia Celular e Molecular) - IBRC

Papel das vias angiotensinérgicas no ventrículo cardíaco esquerdo de ratos submetidos à restrição proteica ou desnutrição gestacional

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)

Efeito agudo de CPAP na funçao diastólica ventricular e na capacidade funcional de pacientes com insuficiência cardíaca

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Influência do tempo de exposição à fumaça de cigarro na remodelação ventricular em ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Influência do antioxidante quercetina sobre a remodelação cardíaca e a atividade oxidativa de ratos com Diabetes mellitus

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeitos do bloqueio precose da aldosterona na estrutura e função cardíaca e na composição da matriz colágena miocárdica de ratos espontaneamente hipertensos

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Mecanismos envolvidos na cardiotoxidade aguda induzida pela doxorrubicina em ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação das metaloproteases 2 e 9 séricas como preditoras da remodelação ventricular seis meses após o infarto agudo do miocárdio

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)