Cardiac dysfunction induced by obesity es not related to beta-adrenergic system impairment at the receptor-signalling pathway

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

Myocardial contractile dysfunction contributes to the development of heart failure in rats with aortic stenosis

Objectives: To analyze the potential contribution of contractility state and ventricular geometry to the development of heart failure in rats with aortic stenosis.Methods: Rats were divided into three groups: compensated aortic stenosis (AS, n = 11), heart failure AS (n = 12) and control rats (C, n = 13).Results: After 21 weeks, failing AS rats presented higher systolic (C = 36.6 +/- 3.1, AS-78.6 +/- 4.8*, failing AS = 104.6 +/- 7.8*) and diastolic meridian stress (C = 6.9 +/- 0.4, AS = 20.1 +/- 1.1*, failing AS = 43.2 +/- 3.2*(dagger)), hydroxyproline (C = 3.6 +/- 0.7 mg/g, AS = 6.6 +/- 0.6* mg/g, failing AS = 9.2 +/- 1.4*(dagger) mg/g) and cross-sectional area (C = 338 +/- 25 mu m(2), AS = 451 +/- 32* mu m(2), failing AS = 508 +/- 36*(dagger) mu m(2)), in comparison with control and compensated AS animals (*p < 0.05 vs. control, (dagger)p < 0.05 vs. AS). In the isometric contraction study, considering the time from peak tension to 50% relaxation (RT50), the relative variation responses, following post-rest contraction and increase in Ca2+ concentration, were higher in failing AS than compensated AS animals. In contrast, following post-rest contraction, compensated AS group presented higher values of the peak developed tension (DT) than failing AS group. Following beta-adrenergic stimulation, control animals presented higher values of +dT/dt and -dT/dt than AS animals. In addition, failing AS animals presented higher TPT values than compensated AS animals.Conclusion: Myocardial contractile dysfunction contributes to the development of heart failure in rats with aortic stenosis. (c) 2006 Elsevier B.V.. All rights reserved.

Exercise Training and Caloric Restriction Prevent Reduction in Cardiac Ca2+-Handling Protein Profile in Obese Rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Involvement of L-Type Calcium Channel and SERCA2a in Myocardial Dysfunction Induced by Obesity

Obesity has been shown to impair myocardial performance. Nevertheless, the mechanisms underlying the participation of calcium (Ca2+) handling on cardiac dysfunction in obesity models remain unknown. L-type Ca2+ channels and sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a), may contribute to the cardiac dysfunction induced by obesity. The purpose of this study was to investigate whether myocardial dysfunction in obese rats is related to decreased activity and/or expression of L-type Ca2+ channels and SERCA2a. Male 30-day-old Wistar rats were fed standard (C) and alternately four palatable high-fat diets (Ob) for 15 weeks. Obesity was determined by adiposity index and comorbidities were evaluated. Myocardial function was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic and lusitropic maneuvers. L-type Ca2+ channels and SERCA2a activity were determined using specific blockers, while changes in the amount of channels were evaluated by Western blot analysis. Phospholamban (PLB) protein expression and the SERCA2a/PLB ratio were also determined. Compared with C rats, the Ob rats had increased body fat, adiposity index and several comorbidities. The Ob muscles developed similar baseline data, but myocardial responsiveness to post-rest contraction stimulus and increased extracellular Ca2+ was compromised. The diltiazem promoted higher inhibition on developed tension in obese rats. In addition, there were no changes in the L-type Ca2+ channel protein content and SERCA2a behavior (activity and expression). In conclusion, the myocardial dysfunction caused by obesity is related to L-type Ca2+ channel activity impairment without significant changes in SERCA2a expression and function as well as L-type Ca2+ protein levels. J. Cell. Physiol. 226: 2934-2942, 2011. (C) 2011 Wiley-Liss, Inc.

Cardiac remodeling in a rat model of diet-induced obesity

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

Toxic mechanism of nickel exposure on cardiac tissue

The incidence of cardiovascular disease has increased in the general population, and cardiac damage is indicated as one important cause of mortality. In addition, pollution and metal exposure have increased in recent years. For this reason, toxic effects of metals, such as nickel, and their relation to cardiac damage should be urgently established. Although free radical-mediated cellular damage and reactive oxygen species have been theorized as contributing to the nickel mechanism of toxicity, recent investigations have established that free radicals may be important contributors to cardiac dysfunction. However, there is little information on the effect of nickel exposure on markers of oxidative stress in cardiac tissue. Nickel exposure (Ni2+ 100 mg L-1 from NiSO4) significantly increased lipoperoxide and total lipid concentrations in cardiac tissue. We also observed increased serum levels of cholesterol (59%), lactate dehydrogenase (LDH-64%), and alanine transaminase (ALT-30%) in study animals. The biochemical parameters recovered to the control values with tocopherol intake (0.2 mg 200 g-1). Vitamin E alone significantly decreased the lipoperoxide concentration and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the heart. Since no alterations were observed in catalase and GSH-Px activities by nickel exposure while SOD activities were decreased, we conclude that superoxide radical (O2 -) generated by nickel exposure is of primary importance in the pathogenesis of cardiac damage. Tocopherol, by its antioxidant activity, decreased the toxic effects of nickel exposure on heart of rats.

Toxic mechanism of cadmium exposure on cardiac tissue

The presence of toxic substances in the workplace environment requires systematic evaluation of exposure and health status in exposed subjects. Cadmium is a highly toxic element found in water. Although free mediated cellular damage and reactive oxygen species (ROS), had been theorized as contributing to the cadmium mechanism of toxicity, and recent investigations have established that free radicals may be important contributors to cardiac dysfunction, there is little information on the effect of cadmium exposure on markers of oxidative stress in cardiac tissue. Cadmium exposure (Cd2+ - 100 mg/1-from CdCl2) in drinking water, during 15 days, significantly increased lipoperoxide and decreased the activities of superoxide dismutase and glutathione peroxidase. No alterations were observed in catalase activity in heart of rats with cadmium exposure. We also observed decreased glycogen and glucose concentration and increased total lipid content in cardiac tissue of rats with cadmium exposure. The decreased activities of alanine transaminase and aspartate transaminase reflected decreased metabolic protein degradation, and increased lactate dehydrogenase activity was related with increases in capacity of glycolysis. Since the metabolic pathways were altered by cadmium exposure, we can conclude that Cd2+ exposure induced ROS and initiate some series of events that occur in the heart and resulted in metabolic pathways alterations.

Cellular and molecular studies of the effects of a selective COX-2 inhibitor celecoxib in the cardiac cell line H9c2 and their correlation with death mechanisms

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Regulation of cardiac microRNAs induced by aerobic exercise training during heart failure

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

Postoperative renal function evaluation, through RIFLE criteria, of elderly patients who underwent femur fracture surgery under spinal anesthesia

Introduction. The postoperative acute renal failure (ARF) incidence in different kinds of surgery has rarely been studied. Age, cardiac dysfunction, previous renal dysfunction, intraoperative hypoperfusion, and use of nephrotoxic medications are mentioned as risk factors for ARF at the postoperative period. The postoperative ARF definition was based on the creatinine increase by the RIFLE classification (R = risk, I = injury, F = failure, L = loss, E = end stage), which corresponds to a 1.5 creatinine increase, two to three times, respectively, above the basal value. This study aimed to evaluate the postoperative ARF incidence in elderly patients who underwent femur fracture surgery under subarachnoid anesthesia and stratify it by the RIFLE criteria. Methods. Ninety patients older than 65 years under spinal anesthesia with fixed dosage of 15 mg of 0.5% isobaric bupivacaine associated with morphine 50 g were studied. Immediate postoperative creatinine was considered basal and compared with maximal creatinine evaluated at 24, 48, and 72 postoperative hours. Results. The mean age of the patients was 80.27 years. ARF incidence was 24.44% and stratified this way: R = 21.11% and I = 3.33%. Conclusions. In conclusion, the postoperative ARF incidence after femur fracture surgery in patients over 65 years was 24.44%. By analyzing the stratification based on the RIFLE classification, the incidence was categorized as Risk (R) = 21.11% and Injury (I) = 3.33%.

Early rather than delayed administration of lisinopril protects the heart after myocardial infarction in rats

Background: ACE inhibitors have shown beneficial results in several studies after myocardial infarction (MI). However, these studies have shown conflicting results about the ideal starting time of the ACE inhibitors administration after MI and the importance of infarct size.Objectives: This study was designed to assess the long-term effects of lisinopril on mortality, cardiac function, and ventricular fibrosis after MI, in rats.Methods: Lisinopril (20 mg/kg/day) was given on day 1 or 21 days after coronary occlusion in small or large infarctions.Results: the mortality rate was reduced by 39% in early treatment and 30% in delayed treatment in comparison to the untreated rats. Early treatment reduced cardiac dysfunction in small MIs; however, delayed treatment did not. No statistical difference was observed among the groups for large MIs. No statistical difference was observed among the groups with large or small MIs on myocardial hydroxyproline concentration.Conclusions: Both early and delayed treatments with lisinopril increased survival. Treatment exerts no marked effects on fibrosis; early treatment has exerted beneficial influences on cardiac function whereas delayed treatment had no consistent effects. The protective effect of lisinopril is detectable only in small (< 40% of LV) MIs.

Critérios ecocardiográficos para definição de graus de disfunção ventricular em ratos portadores de estenose aórtica

OBJETIVO: O objetivo deste estudo foi identificar variáveis ecocardiográficas que definam graus de disfunção cardíaca em ratos com estenose aórtica (EAo). MÉTODOS: Ratos Wistar (n = 23), machos (90-100 g), foram submetidos a cirurgia para indução de EAo. As variáveis ecocardiográficas analisadas foram: diâmetros diastólico do ventrículo esquerdo (DDVE) e sistólico do átrio esquerdo em valores absolutos e normalizados para o peso corporal; diâmetro sistólico do VE (DSVE); três índices de encurtamento do VE (% de encurtamento endocárdico, %Enc.Endo; % de encurtamento miocárdico, %Enc.Mio; e velocidade de encurtamento da parede posterior do VE, VEPP); e índice de massa do VE (IMVE). Essas variáveis foram utilizadas para a análise de agrupamento (cluster analysis). RESULTADOS: A análise de agrupamento possibilitou separar os ratos com EAo em dois grupos: disfunção leve (n = 13) e disfunção severa (n = 9). Os intervalos de confiança das seguintes variáveis não apresentaram superposição dos seus valores: DDVE, DSVE, %Enc.Endo, %Enc.Mio, IMVE e VEPP. CONCLUSÃO: A utilização conjunta dos intervalos de confiança dessas variáveis permite identificar dois grupos de ratos com estenose aórtica e diferentes graus de comprometimento cardíaco, possibilitando a realização de estudos longitudinais com grupos homogêneos de animais.

Food restriction promotes downregulation of myocardial L-type Ca2+ channels

Food restriction (FR) has been shown to impair myocardial performance. However, the mechanisms behind these changes in myocardial function due to FR remain unknown. Since myocardial L-type Ca2+ channels may contribute to the cardiac dysfunction, we examined the influence of FR on L-type Ca2+ channels. Male 60-day-old Wistar rats were fed a control 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 evaluated in isolated left ventricular papillary muscles. The function of myocardial L-type Ca2+ channels was determined by using a pharmacological Ca2+ channel blocker, and changes in the number of channels were evaluated by mRNA and protein expression. FR decreased final body weights, as well as weights of the left and right ventricles. The Ca2+ channel blocker diltiazem promoted a higher blockade on developed tension in FR groups than in controls. The protein content of L-type Ca2+ channels was significantly diminished in FR rats, whereas the mRNA expression was similar between groups. These results suggest that the myocardial dysfunction observed in previous studies with FR animals could be caused by downregulation of L-type Ca2+ channels.