Influence of N-acetylcysteine on oxidative stress in slow-twitch soleus muscle of heart failure rats

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

Long-term low intensity physical exercise attenuates heart failure development in aging spontaneously hypertensive rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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.

Assessment of structural cardiac abnormalities and diastolic function in women with gestational diabetes mellitus

Background: The main manifestation of hyperglycaemia during pregnancy is gestational diabetes mellitus. It can herald diabetes mellitus type 2 and its deleterious long-term effects, such as hypertension and cardiovascular disease. The aim of this study was to assess diastolic function in women with gestational diabetes mellitus, one of the first signs of future cardiovascular disease.Methods: A total of 21 women with gestational diabetes mellitus and 23 healthy pregnant women (control group) between 34 and 37weeks of gestation underwent echocardiographic assessment. The diagnosis of gestational diabetes mellitus was made in agreement with the American Diabetes Association criteria. Echocardiographic images obtained were analysed according to the criteria of the American Society of Echocardiography. Data were analysed using Pearson correlation coefficient, analysis of variance and Student's t-test.Results: Women with gestational diabetes mellitus had higher posterior wall and interventricular septum thickness, increased left ventricular mass and left ventricular mass index, lower early diastolic annular velocity and early diastolic annular velocity/late diastolic annular velocity ratio. There was a positive correlation between left ventricular mass index and fasting glucose and pregnancy body mass index.Conclusion: Patients with gestational diabetes mellitus seem to have a different diastolic profile as well as a mildly dysfunctional pattern on echocardiogram, which may show a need for greater glycaemic control.

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)

Evaluation of Cardiovascular Function During S(+)-Ketamine Constant Rate Infusion in Dorsally Recumbent Halothane-Anesthetized Horses

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The effect of non-antihypertensive doses of angiotensin converting enzyme inhibitor on myocardial necrosis and hypertrophy in young rats with renovascular hypertension

In renovascular hypertensive rats, low doses of angiotensin converting enzyme (ACE) inhibitors have been found to prevent myocardial hypertrophy independent of blood pressure level. This finding would suggest humoral rather than mechanical control of myocyte growth. The aim of this study was to examine the effect of nonantihypertensive doses of ACE inhibitor on myocardial hypertrophy and necrosis in hypertensive rats. Renovascular hypertension (RHT) was induced in four-week-old Wistar rats. Twenty-eight animals were treated for four weeks with three doses of ramipril (0.01, 0.1 or 1. 0 mg/kg/day, which are unable to lower blood pressure. Fourteen animals were not treated (RHT group). A sham operated, age/sex-matched group was used as control (n = 10). Myocardial histology was analysed in 3 microm thick sections of the ventricle stained with either haematoxylin-eosin, reticulin silver stain or Masson's trichrome. There was a significant correlation between systolic blood pressure and left ventricular to body weight ratio in both sets of animals: untreated plus controls and ramipril-treated rats. ACE inhibition prevented myocyte and perivascular necrosis and fibrosis in a dose-dependent manner. We conclude that myocardial hypertrophy in rats with renovascular hypertension is directly related to arterial pressure, and that this relationship is not affected by nonantihypertensive doses of ACE inhibitor. Myocardial necrosis/fibrosis and coronary artery damage induced by angiotensin II are prevented by ACE inhibitor in a dose-dependent manner, despite the presence of arterial hypertension.

Direct effects of colchicine on myocardial function: studies in hypertrophied and failing spontaneously hypertensive rats

The aging spontaneously hypertensive rat (SHR) is a model in which the transition from chronic stable left ventricular hypertrophy to overt heart failure can be observed. Although the mechanisms for impaired function in hypertrophied and failing cardiac muscle from the SHR have been studied, none accounts fully for the myocardial contractile abnormalities. The cardiac cytoskeleton has been implicated as a possible cause for myocardial dysfunction. If an increase in microtubules contributes to dysfunction, then myocardial microtubule disruption by colchicine should promote an improvement in cardiac performance. We studied the active and passive properties of isolated left ventricular papillary muscles from 18- to 24-month-old SHR with evidence of heart failure (SHR-F, n=6), age-matched SHR without heart failure (SHR-NF, n=6), and age-matched normotensive Wistar-Kyoto rats (WKY, n=5). Mechanical parameters were analyzed before and up to 90 minutes after the addition of colchicine (10(-5), 10(-4), and 10(-3) mol/L). In the baseline state, active tension (AT) developed by papillary muscles from the WKY group was greater than for SHR-NF and SHR-F groups (WKY 5.69+/-1.47 g/mm2 [mean+/-SD], SHR-NF 3.41+/-1.05, SHR-F 2.87+/-0.26; SHR-NF and SHR-F P<0.05 versus WKY rats). The passive stiffness was greater in SHR-F than in the WKY and SHR-NF groups (central segment exponential stiffness constant, Kcs: SHR-F 70+/-25, SHR-NF 44+/-17, WKY 41+/-13 [mean+/-SD]; SHR-F P<0.05 versus SHR-NF and WKY rats). AT did not improve after 10, 20, and 30 minutes of exposure to colchicine (10(-5), 10(-4), and 10(-3) mol/L) in any group. In the SHR-F group, AT and passive stiffness did not change after 30 to 90 minutes of colchicine exposure (10(-4) mol/L). In summary, the data in this study fail to demonstrate improvement of intrinsic muscle function in SHR with heart failure after colchicine. Thus, in the SHR there is no evidence that colchicine-induced cardiac microtubular depolymerization affects the active or passive properties of hypertrophied or failing left ventricular myocardium.

Low intensity physical exercise attenuates cardiac remodeling and myocardial oxidative stress and dysfunction in diabetic rats

We evaluated the effects of a low intensity aerobic exercise protocol on cardiac remodeling and myocardial function in diabetic rats. Wistar rats were assigned into four groups: sedentary control (C-Sed), exercised control (C-Ex), sedentary diabetes (DM-Sed), and exercised diabetes (DM-Ex). Diabetes was induced by intraperitoneal injection of streptozotocin. Rats exercised for 9 weeks in treadmill at 11 m/min, 18 min/day. Myocardial function was evaluated in left ventricular (LV) papillary muscles and oxidative stress in LV tissue. Statistical analysis was given by ANOVA or Kruskal-Wallis. Echocardiogram showed diabetic groups with higher LV diastolic diameter-to-body weight ratio and lower posterior wall shortening velocity than controls. Left atrium diameter was lower in DM-Ex than DM-Sed (C-Sed: 5.73 ± 0.49; C-Ex: 5.67 ± 0.53; DM-Sed: 6.41 ± 0.54; DM-Ex: 5.81 ± 0.50 mm; P < 0.05 DM-Sed vs C-Sed and DM-Ex). Papillary muscle function was depressed in DM-Sed compared to C-Sed. Exercise attenuated this change in DM-Ex. Lipid hydroperoxide concentration was higher in DM-Sed than C-Sed and DM-Ex. Catalase and superoxide dismutase activities were lower in diabetics than controls and higher in DM-Ex than DM-Sed. Glutathione peroxidase activity was lower in DM-Sed than C-Sed and DM-Ex. Conclusion. Low intensity exercise attenuates left atrium dilation and myocardial oxidative stress and dysfunction in type 1 diabetic rats.

Influência do exercício físico na remodelação cardíaca induzida pelo ácido retinóico

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

Influência do exercício físico sobre o estresse oxidativo, as MAPK e o NF-kB no músculo sóleo de ratos com insuficiência cardíaca induzida por estenose aórtica

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

Influência da suplementação de açaí (Euterpe oleracea Mart.) na ração sobre remodelação cardíaca em ratos expostos à fumaça do cigarro

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Fatores de risco cardiovascular em mulheres com antecedente de pré-eclâmpsia e sua associação com hipertrofia miocárdica e espessamento médio-intimal de carótidas

Pós-graduação em Fisiopatologia em Clínica Médica - FMB

Impacto do exercício físico combinado na função diastólica de pacientes com insuficiência cardíaca e fração de ejeção reduzida

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

Avaliação de cardiotoxicidade subclínica tardia em pacientes com diagnóstico prévio de linfoma não Hodgkin tratados com antraciclinas

Pós-graduação em Fisiopatologia em Clínica Médica - FMB