Assesment of the TEI index of myocardial performance in dogs with doxorubicin-induced cardiomiopathy

The development of a dose-dependent cardiomyopathy is the main limitation for the use of doxorubicin in chemotherapy protocols in both humans and animals. In this setting, the global myocardial function may be compromised resulting in signs of congestive heart failure. In this study, we investigated the ability of the Tei index of myocardial performance to identify myocardial dysfunction in healthy dogs receiving doxorubicin to a cumulative dose of 210 mg/m(2) over 147 days, comparing it with other standard echocardiographic indicators of systolic and diastolic function. Our results indicated that the Tei index, the isovolumic relaxation time, pre-ejection period and the pre-ejection period-to-left ventricular ejection time ratio were able to identify the cardiotoxic effects of doxorubicin on cardiac function when only 60 mg/m(2) had been administered, while the standard systolic and diastolic parameters, including left ventricular diameter at systole, ejection fraction, and fractional shortening needed at least 120 mg/mg(2) to deteriorate. We concluded that prolonged anthracycline therapy compromises both systolic and diastolic functions, which may be documented earlier by including the Tel index evaluation to the standard echocardiographic assessment of animals receiving doxorubicin.

Effects of an isotonic beverage on autonomic regulation during and after exercise

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

The effects of different inspired oxygen fractions on gas exchange and Tei-index of myocardial performance in propofol-anesthetized dogs

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Influência do exercício físico sobre variáveis funcionais, morfológicas e moleculares do coração de ratos idosos

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Controle autonômico do coração e fração de ejeção na fase crônica do acidente vascular encefálico

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

Aerobic Exercise Training Prevents Heart Failure-Induced Skeletal Muscle Atrophy by Anti-Catabolic, but Not Anabolic Actions

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

Antidepressivo em ratos com insuficiência aórtica pode modificar a expressão gênica de ocitocina e vasopressina centrais?

Aortic regurgitation (AR) leads to a left ventricle dilation and hypertrophy in response to a chronic volume overload. It is still very frequent in developing countries, for instance Brazil, and often as secondary to rheumatic fever. Usually, chronic AR is generally well tolerated for many years, when with the heart dilated the patient searches for treatment. Bidirectional association with depression and cardiovascular disease has been described. Selective serotonin reuptake inhibitors (SSRI) are widely prescribed to treat several affective disorders, especially for cardiovascular patients since they decrease arrhythmia probability. These SSRI improves cardiac function in rats submitted to stress protocols. Preliminary study from our laboratory showed that following 4 weeks of treatment with one SSRI (paroxetine) in subchronic AR rats there was a decreased in daily sodium intake and an improvement in systolic function. An increase in the central oxytocinergic transmission may be involved in this peripheral improvement to the heart. The investigations about the mechanisms underlying this improvement are necessary. Therefore the aims of this project is investigate the effects of 4 weeks of treatment of paroxetine, a SSRI, in rats with a subchronic AR over the central central gene expression of oxytocin and vasopressin using a reverse transcription polymerase chain reaction (RT-PCR)

Antidepressivo modula o comportamento e a expressão gênica das cadeias de miosina, serca2 e fosfolambam em ratos com insuficiência aórtica?

Introduction: Aortic insufficiency (AoI), a volume overload, is characterized by the diastolic reflux of blood from the regurgitating aorta to the left ventricle. This effect results from malfunctioning aortic cusps. The main cause of AoI in developing countries is rheumatic fever, including Brazil, and valvar degeneration in developed countries. There is a strong association between cardiovascular diseases and depression. Selective serotonin reuptake inhibitors (SSRI) are one of the most prescribed antidepressants in the world. Previous studies of our laboratory showed that the utilization of a SSRI, paroxetine, improved cardiac function in rats with sub-chronic AoI and reduced the daily ingestion of hypertonic sodium (NaCl 0,3M). Cardiovascular diseases can determine behavior changes like increase of anxiety, and it is yet unknown if AoI would determine anxiety or anhedonia, incapacity of obtaining pleasure through physical or sensorial experiences. A possible target for SSRI action could be a change in the expression of enzyme isoforms that collaborate in the contractile function of the heart muscle, like the heavy chains of myosine, the sarcoplasmatic reticulum Ca2+/ATPase (SERCA) and its regulator protein, phospholamban (PLB). Objectives: Evaluation of behavior parameters for anxiety and anhedonia state and genic expression of a-myosine, b-myosine, SERCA2a and PLB in the heart tissue of rats with subchronic AoI that received treatment with an SSRI (paroxetine) for 4 weeks. Methods: Surgery to induce AoI was performed on male Wistar rats, anxiety was evaluated by the elevated plus-maze (EPM) and state of anhedonia was tested by ingestion of 2% sucrose solution. After euthanasia the heart tissue was collected and total RNA was extracted to be analyzed by the RT-qPCR method. Results: Heart fractional shortening was preserved in rats with AoI that were treated compared to rats with AoI that were not treated. There was no statistically ...

Influência da obesidade induzida por dieta hiperlipídica saturada sobre o comportamento da via beta-adrenérgica miocárdica em ratos Wistar

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Acute doxorubicin-induced cardiotoxicity is associated with matrix metalloproteinase-2 alterations in rats

Background: Doxorubicin can cause cardiotoxicity. Matrix metalloproteinases (MMP) are responsible for degrading extracellular matrix components which play a role in ventricular dilation. Increased MMP activity occurs after chronic doxorubicin treatment. In this study we evaluated in vivo and in vitro cardiac function in rats with acute doxorubicin treatment, and examined myocardial MMP and inflammatory activation, and gene expression of proteins involved in myocyte calcium transients. Methods: Wistar rats were injected with doxorubicin (Doxo, 20 mg/kg) or saline (Control). Echocardiogram was performed 48 h after treatment. Myocardial function was assessed in vitro in Langendorff preparation. Results: In left ventricle, doxorubicin impaired fractional shortening (Control 0.59 +/- 0.07; Doxo 0.51 +/- 0.05; p < 0.001), and increased isovolumetric relaxation time (Control 20.3 +/- 4.3; Doxo 24.7 +/- 4.2 ms; p = 0.007) and myocardial passive stiffness. MMP-2 activity, evaluated by zymography, was increased in Doxo (Control 141338 +/- 8924; Doxo 188874 +/- 7652 arbitrary units; p < 0.001). There were no changes in TNF-alpha, INF-gamma, IL-10, and ICAM-1 myocardial levels. Expression of phospholamban, Serca-2a, and ryanodine receptor did not differ between groups. Conclusion: Acute doxorubicin administration induces in vivo left ventricular dysfunction and in vitro increased myocardial passive stiffness in rats. Cardiac dysfunction is related to myocardial MMP-2 activation. Increased inflammatory stimulation or changed expression of the proteins involved in intracellular calcium transients is not involved in acute cardiac dysfunction.

Antidepressant treatment decreases daily salt intake and prevents heart dysfunction following subchronic aortic regurgitation in rats

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

Surgical interventions for treating pectus excavatum

Background: Pectus excavatum is characterized by a depression of the anterior chest wall (sternum and lower costal cartilages) and is the most frequently occurring chest wall deformity. The prevalence ranges from 6.28 to 12 cases per 1000 around the world. Generally pectus excavatum is present at birth or is identified after a few weeks or months; however, sometimes it becomes evident only at puberty. The consequence of the condition on a individual's life is variable, some live a normal life and others have physical and psychological symptoms such as: precordial pain after exercises; impairments of pulmonary and cardiac function; shyness and social isolation. For many years, sub-perichondrial resection of the costal cartilages, with or without transverse cuneiform osteotomy of the sternum and placement of a substernal support, called conventional surgery, was the most accepted option for surgical repair of these patients. From 1997 a new surgical repair called, minimally invasive surgery, became available. This less invasive surgical option consists of the retrosternal placement of a curved metal bar, without resections of the costal cartilages or sternum osteotomy, and is performed by videothoracoscopy. However, many aspects that relate to the benefits and harms of both techniques have not been defined. Objectives: To evaluate the effectiveness and safety of the conventional surgery compared with minimally invasive surgery for treating people with pectus excavatum. Search methods: With the aim of increasing the sensitivity of the search strategy we used only terms related to the individual's condition (pectus excavatum); terms related to the interventions, outcomes and types of studies were not included. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, LILACS, and ICTPR. Additionally we searched yet reference lists of articles and conference proceedings. All searches were done without language restriction. Date of the most recent searches: 14 January 2014. Selection criteria: We considered randomized or quasi-randomized controlled trials that compared traditional surgery with minimally invasive surgery for treating pectus excavatum. Data collection and analysis: Two review authors independently assessed the eligibility of the trials identified and agreed trial eligibility after a consensus meeting. The authors also assessed the risk of bias of the eligible trials. Main results: Initially we located 4111 trials from the electronic searches and two further trials from other resources. All trials were added into reference management software and the duplicates were excluded, leaving 2517 studies. The titles and abstracts of these 2517 studies were independently analyzed by two authors and finally eight trials were selected for full text analysis, after which they were all excluded, as they did not fulfil the inclusion criteria. Authors' conclusions: There is no evidence from randomized controlled trials to conclude what is the best surgical option to treat people with pectus excavatum.

Surgical interventions for treating pectus excavatum

Pectus excavatum is characterized by a depression of the anterior chest wall (sternum and lower costal cartilages) and is the most frequently occurring chest wall deformity. The prevalence ranges from 6.28 to 12 cases per 1000 around the world. Generally pectus excavatum is present at birth or is identified after a few weeks or months; however, sometimes it becomes evident only at puberty. The consequence of the condition on a individual’s life is variable, some live a normal life and others have physical and psychological symptoms such as: precordial pain after exercises; impairments of pulmonary and cardiac function; shyness and social isolation. For many years, sub-perichondrial resection of the costal cartilages, with or without transverse cuneiform osteotomy of the sternum and placement of a substernal support, called conventional surgery, was the most accepted option for surgical repair of these patients. From 1997 a new surgical repair called, minimally invasive surgery, became available. This less invasive surgical option consists of the retrosternal placement of a curved metal bar, without resections of the costal cartilages or sternum osteotomy, and is performed by videothoracoscopy. However, many aspects that relate to the benefits and harms of both techniques have not been defined. Objectives To evaluate the effectiveness and safety of the conventional surgery compared with minimally invasive surgery for treating people with pectus excavatum. Search methods With the aim of increasing the sensitivity of the search strategy we used only terms related to the individual’s condition (pectus excavatum); terms related to the interventions, outcomes and types of studies were not included. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, LILACS, and ICTPR. Additionally we searched yet reference lists of articles and conference proceedings. All searches were done without language restriction.

Disfunção miocárdica e alterações no trânsito de cálcio intracelular em ratos obesos

Abstract Background: Several mechanisms have been proposed to contribute to cardiac dysfunction in obesity models, such as alterations in calcium (Ca2+) handling proteins and β-adrenergic receptors. Nevertheless, the role of these factors in the development of myocardial dysfunction induced by obesity is still not clear. Objective: The purpose of this study was to investigate whether obesity induced by hypercaloric diets results in cardiac dysfunction. Furthermore, it was evaluated whether this functional abnormality in obese rats is related to abnormal Ca2+ handling and the β-adrenoceptor system. Methods: Male 30-day-old Wistar rats were fed with standard food (C) and a cycle of five hypercaloric diets (Ob) for 15 weeks. Obesity was defined as increases in body fat percentage in rats. Cardiac function was evaluated by isolated analysis of the left ventricle papillary muscle under basal conditions and after inotropic and lusitropic maneuvers. Results: Compared with the control group, the obese rats had increased body fat and glucose intolerance. The muscles of obese rats developed similar baseline data, but the myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca2+ were compromised. There were no changes in cardiac function between groups after β-adrenergic stimulation. Conclusion: Obesity promotes cardiac dysfunction related to changes in intracellular Ca2+ handling. This functional damage is probably caused by reduced cardiac sarcoplasmic reticulum Ca2+ ATPase (SERCA2) activation via Ca2+ calmodulin kinase. (Arq Bras Cardiol 2011; 97(3) : 232-240).

Intervenções cirúrgicas para o tratamento do pectus excavatum: revisão sistemática

Pós-graduação em Bases Gerais da Cirurgia - FMB