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1.
Mol Med Rep ; 21(3): 1431-1438, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32016473

RESUMO

Among the mechanisms of action of hyperbaric oxygenation (HBO), the chance of reducing injury by interfering with the mechanisms of redox homeostasis in the heart leads to the possibility of extending the period of viability of the myocardium at risk. This would benefit late interventions for reperfusion to the ischemic area. The objective of the present study was to investigate the changes in the redox system associated with HBO therapy maintained during the first hour after coronary occlusion in an acute myocardial infarction (MI) rat model. Surviving male rats (n=105) were randomly assigned to one of three groups: Sham (SH=26), myocardial infarction (MI=45) and infarction+hyperbaric therapy (HBO=34, 1 h at 2.5 atm). After 90 min of coronary occlusion, a sample of the heart was collected for western blot analysis of total protein levels of superoxide dismutase, catalase, peroxiredoxin and 3­nitrotyrosine. Glutathione was measured by enzyme­linked immunosorbent assay (ELISA). The detection of the superoxide radical anion was carried out by oxidation of dihydroethidium analyzed with confocal microscopy. The mortality rate of the MI group was significantly higher than that of the HBO group. No difference was noted in the myocardial infarction size. The oxidized/reduced glutathione ratio and peroxiredoxin were significantly higher in the SH and MI when compared to the HBO group. Superoxide dismutase enzymes and catalase were significantly higher in the HBO group compared to the MI and SH groups. 3­Nitrotyrosine and the superoxide radical were significantly lower in the HBO group compared to these in the MI and SH groups. These data demonstrated that hyperbaric oxygenation therapy decreased mortality by improving redox control in the hearts of rats in the acute phase of myocardial infarction.

2.
J Hypertens ; 38(1): 73-81, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31335510

RESUMO

BACKGROUND AND METHOD: This study evaluated the effects of a linear block strength training programme on the parameters of cardiac remodelling in spontaneously hypertensive rats. Thirty-nine rats were equally distributed in four groups: normotensive sedentary, normotensive trained, hypertensive sedentary and hypertensive trained. The strength training protocol was organized in three mesocycles of 4 weeks, with an increase in the training load organized in a linear fashion for each block, considering the weight established in the maximum loaded load test. The following parameters were evaluated: ventricular function assessed by echocardiogram, caudal blood pressure, ventricular haemodynamics and cardiac masses. Two-way analysis of variance was used to determine the differences between the group and time. RESULTS: After 12 weeks of training, the hypertensive trained group presented the following results: increased muscle strength, reduced blood pressure, reduced heart rate, isovolumetric relaxation time and total collagen content, with increased cardiac function, without promoting changes in the mass and nuclear volume of cardiomyocytes. Also, blood pressure reduction seems to be associated with both muscle strength adjustments and total load progress. CONCLUSION: The findings of this study showed that the training programme carried out attenuated systemic arterial pressure and preserved the ventricular function of spontaneously hypertensive rats without cardiac mass change.

3.
J Cardiovasc Pharmacol Ther ; : 1074248419887708, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714152

RESUMO

We previously showed that digitoxin prolongs the survival of rats with heart failure due to myocardial infarction (MI). In this study, we evaluated the effect of digitoxin on myocardial structure, ventricular function, and proteins involved in calcium kinetics. Seventy-two rats with MI >35% of the left ventricle were randomly assigned to 4 treatment groups: sham (n = 15), digitoxin (n = 11), infarction (n = 20), and infarction + digitoxin (n = 26). The rats were assessed 120 days after surgery by echocardiogram, hemodynamics, papillary muscle mechanics, collagen content, cardiomyocyte nuclear volume, and Western blot analysis of proteins involved in calcium kinetics. Digitoxin was administered via the rat chow. Two-way analysis of variance was used for comparisons. Myocardial infarction caused inotropic impairment, pulmonary congestion, increase of nuclear volume, myocardial collagen, and Na+/Ca2+ exchanger levels, and decreased SERCA2 and phosphorylated phospholamban levels. Treatment with digitoxin showed improvements in cardiac remodeling, inotropism, ventricular performance, pulmonary congestion, collagen accumulation, nuclear volume, and proteins involved in calcium kinetics. In rats with heart failure due to MI, long-term treatment with digitoxin attenuates congestive heart failure, mitigates myocardial remodeling and contractile impairment, and preserves myocardial levels of proteins involved in calcium kinetics.

4.
Front Physiol ; 10: 157, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30899225

RESUMO

The present study aimed to analyze the effects of reperfusion of a distant coronary artery on cardiac function, the ultrastructure, and the molecular environment of the remote myocardium immediately after the completion of myocardial regional necrosis: delayed reperfusion (DR). Additionally, the effects of prior exercise on the outcomes of DR were investigated. Female rats with permanent occlusion or delayed reperfusion were randomly assigned to an exercise (swimming, 1 h/day, 5 days/week for 8 weeks) or sedentary protocol. Thus, the study included the following four groups: sedentary permanent occlusion, exercise permanent occlusion, sedentary delayed reperfusion, and exercise delayed reperfusion. The descending coronary artery was occluded for 1 h. Reperfusion was confirmed by contrast echocardiography, and the rats were observed for 4 weeks. Permanent occlusion and DR caused similar myocardial infarction sizes among the four groups. Interestingly, exercise significantly decreased the mortality rate. Delayed reperfusion resulted in significant benefits, including enhanced hemodynamics and papillary muscle contraction, as well as reduced apoptosis and collagen content. Protein calcium kinetics did not change. Meanwhile, developed tension and the Frank-Starling mechanism were enhanced, suggesting that calcium sensitivity was intensified in myofilaments. Remarkable remote myocardial benefits occurred after distant DR, and prior exercise intensified cardiac recovery. Our findings provide valuable information about DR. Our data might explain the better clinical outcomes in recent studies showing that late reperfusion could improve heart failure in patients with myocardial infarction. In conclusion, DR has remote myocardial benefits, including inotropism enhancement, pulmonary congestion reduction, and collagen and apoptosis attenuation, which are enhanced by prior exercise.

5.
Int J Cardiol Heart Vasc ; 21: 22-28, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30258978

RESUMO

Background: Atrial fibrillation (AF) frequently coexists with congestive heart failure (CHF). The increased susceptibility to AF in CHF has been attributed to a variety of structural and electrophysiological changes in the atria, particularly dilation and interstitial fibrosis. We evaluated atrial remodeling and AF vulnerability in a rat model of CHF induced by left ventricle (LV) radiofrequency (RF) ablation. Methods: Wistar rats were divided into 3 groups: RF-induced CHF (Ab, n = 36), CHF animals treated with spironolactone (AbSpi, n = 20) and sham controls (Sham, n = 29). After 12 weeks, animals underwent echocardiographic and electrophysiological evaluation and were sacrificed for histological (atrial fibrosis) and Western blotting (TGF-ß1, collagen I/III, connexin 43 and CaV1.2) analysis. Results: Mild LV dysfunction and marked atrial enlargement were noted in both ablated groups. AF inducibility (episodes ≥2 s) increased in the Ab group compared to sham animals (31/36, 86%; vs. 15/29, 52%; p = 0.005), but did not differ from the AbSpi group (16/20, 80%; p = NS). Sustained AF (>30 s) was also more frequent in the Ab group compared to shams (56% vs. 28%; p = 0.04). Spironolactone reduced atrial fibrosis (p < 0.01) as well as TGF-ß1 (p < 0.01) and collagen I/III (p < 0.01) expression but did not affect connexin 43 and CaV1.2 expression. Conclusions: Rats with RF-induced CHF exhibit pronounced atrial structural remodeling and enhanced AF vulnerability. This model may be useful for studying AF substrate in CHF.

6.
Front Physiol ; 8: 23, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28194115

RESUMO

Low-level laser therapy (LLLT) has been targeted as a promising approach that can mitigate post-infarction cardiac remodeling. There is some interesting evidence showing that the beneficial role of the LLLT could persist long-term even after the end of the application, but it remains to be systematically evaluated. Therefore, the present study aimed to test the hypothesis that LLLT beneficial effects in the early post-infarction cardiac remodeling could remain in overt heart failure even with the disruption of irradiations. Female Wistar rats were subjected to the coronary occlusion to induce myocardial infarction or Sham operation. A single LLLT application was carried out after 60 s and 3 days post-coronary occlusion, respectively. Echocardiography was performed 3 days and at the end of the experiment (5 weeks) to evaluate cardiac function. After the last echocardiographic examination, LV hemodynamic evaluation was performed at baseline and on sudden afterload increases. Compared with the Sham group, infarcted rats showed increased systolic and diastolic internal diameter as well as a depressed shortening fraction of LV. The only benefit of the LLLT was a higher shortening fraction after 3 days of infarction. However, treated-LLLT rats show a lower shortening fraction in the 5th week of study when compared with Sham and non-irradiated rats. A worsening of cardiac function was confirmed in the hemodynamic analysis as evidenced by the higher LV end-diastolic pressure and lower +dP/dt and -dP/dt with five weeks of study. Cardiac functional reserve was also impaired by infarction as evidenced by an attenuated response of stroke work index and cardiac output to a sudden afterload stress, without LLLT repercussions. No significant differences were found in the myocardial expression of Akt1/VEGF pathway. Collectively, these findings illustrate that LLLT improves LV systolic function in the early post-infarction cardiac remodeling. However, this beneficial effect may be dependent on the maintenance of phototherapy. Long-term studies with LLLT application are needed to establish whether these effects ultimately translate into improved cardiac remodeling.

7.
Front Physiol ; 7: 541, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27994552

RESUMO

Introduction: Pulmonary arterial stenosis (PAS) is a congenital defect that causes outflow tract obstruction of the right ventricle (RV). Currently, negative issues are reported in the PAS management: not all patients may be eligible to surgeries; there is often the need for another surgery during passage to adulthood; patients with mild stenosis may have later cardiac adverse repercussions. Thus, the search for approaches to counteract the long-term PAS effects showed to be a current target. At the study herein, we evaluated the cardioprotective role of exercise training in rats submitted to PAS for 9 weeks. Methods and Results: Exercise resulted in improved physical fitness and systolic RV function. Exercise also blunted concentric cavity changes, diastolic dysfunction, and fibrosis induced by PAS. Exercise additional benefits were also reported in a pro-survival signal, in which there were increased Akt1 activity and normalized myocardial apoptosis. These findings were accompanied by microRNA-1 downregulation and microRNA-21 upregulation. Moreover, exercise was associated with a higher myocardial abundance of the sarcomeric protein α-MHC and proteins that modulate calcium handling-ryanodine receptor and Serca 2, supporting the potential role of exercise in improving myocardial performance. Conclusion: Our results represent the first demonstration that exercise can attenuate the RV remodeling in an experimental PAS. The cardioprotective effects were associated with positive modulation of RV function, survival signaling pathway, apoptosis, and proteins involved in the regulation of myocardial contractility.

8.
Front Physiol ; 7: 565, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27932994

RESUMO

The ligation of the left anterior descending coronary artery is the most commonly used experimental model to induce myocardial infarction (MI) in rodents. A high mortality in the acute phase and the heterogeneity of the size of the MI obtained are drawbacks recognized in this model. In an attempt to solve the problem, our group recently developed a new MI experimental model which is based on application of myocardial ablation radio-frequency currents (AB-RF) that yielded MI with homogeneous sizes and significantly reduce acute mortality. In addition, cardiac structural, and functional changes aroused by AB-RF were similar to those seen in animals with MI induced by coronary artery ligation. Herein, we compared mRNA expression of genes that govern post-MI milieu in occlusion and ablation models. We analyzed 48 mRNAs expressions of nine different signal transduction pathways (cell survival and metabolism signs, matrix extracellular, cell cycle, oxidative stress, apoptosis, calcium signaling, hypertrophy markers, angiogenesis, and inflammation) in rat left ventricle 1 week after MI generated by both coronary occlusion and AB-RF. Furthermore, high-throughput miRNA analysis was also assessed in both MI procedures. Interestingly, mRNA expression levels and miRNA expressions showed strong similarities between both models after MI, with few specificities in each model, activating similar signal transduction pathways. To our knowledge, this is the first comparison of genomic alterations of mRNA and miRNA contents after two different MI procedures and identifies key signaling regulators modulating the pathophysiology of these two models that might culminate in heart failure. Furthermore, these analyses may contribute with the current knowledge concerning transcriptional and post-transcriptional changes of AB-RF protocol, arising as an alternative and effective MI method that reproduces most changes seem in coronary occlusion.

9.
Front Physiol ; 7: 293, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27462276

RESUMO

Circulating dipeptidyl peptidase IV (DPPIV) activity is associated with worse cardiovascular outcomes in humans and experimental heart failure (HF) models, suggesting that DPPIV may play a role in the pathophysiology of this syndrome. Renal dysfunction is one of the key features of HF, but it remains to be determined whether DPPIV inhibitors are capable of improving cardiorenal function after the onset of HF. Therefore, the present study aimed to test the hypothesis that DPPIV inhibition by vildagliptin improves renal water and salt handling and exerts anti-proteinuric effects in rats with established HF. To this end, male Wistar rats were subjected to left ventricle (LV) radiofrequency ablation or sham operation. Six weeks after surgery, radiofrequency-ablated rats who developed HF were randomly divided into two groups and treated for 4 weeks with vildagliptin (120 mg/kg/day) or vehicle by oral gavage. Echocardiography was performed before (pretreatment) and at the end of treatment (post-treatment) to evaluate cardiac function. The fractional area change (FAC) increased (34 ± 5 vs. 45 ± 3%, p < 0.05), and the isovolumic relaxation time decreased (33 ± 2 vs. 27 ± 1 ms; p < 0.05) in HF rats treated with vildagliptin (post-treatment vs. pretreatment). On the other hand, cardiac dysfunction deteriorated further in vehicle-treated HF rats. Renal function was impaired in vehicle-treated HF rats as evidenced by fluid retention, low glomerular filtration rate (GFR) and high levels of urinary protein excretion. Vildagliptin treatment restored urinary flow, GFR, urinary sodium and urinary protein excretion to sham levels. Restoration of renal function in HF rats by DPPIV inhibition was associated with increased active glucagon-like peptide-1 (GLP-1) serum concentration, reduced DPPIV activity and increased activity of protein kinase A in the renal cortex. Furthermore, the anti-proteinuric effect of vildagliptin treatment in rats with established HF was associated with upregulation of the apical proximal tubule endocytic receptor megalin and of the podocyte main slit diaphragm proteins nephrin and podocin. Collectively, these findings demonstrate that DPPIV inhibition exerts renoprotective effects and ameliorates cardiorenal function in rats with established HF. Long-term studies with DPPIV inhibitors are needed to ascertain whether these effects ultimately translate into improved clinical outcomes.

10.
Clinics (Sao Paulo) ; 71(3): 163-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27074178

RESUMO

OBJECTIVE: Exercise is a protective factor for cardiovascular morbidity and mortality, with unclear mechanisms. Changing the myocardial metabolism causes harmful consequences for heart function and exercise contributes to metabolic adjustment modulation. Peroxisome proliferator-activated receptors (PPARs) are also myocardium metabolism regulators capable of decreasing the inflammatory response. We hypothesized that PPAR-α is involved in the beneficial effects of previous exercise on myocardial infarction (MI) and cardiac function, changing the expression of metabolic and inflammatory response regulators and reducing myocardial apoptosis, which partially explains the better outcome. METHODS AND RESULTS: Exercised rats engaged in swimming sessions for 60 min/day, 5 days/week, for 8 weeks. Both the exercised rats and sedentary rats were randomized to MI surgery and followed for 1 week (EI1 or SI1) or 4 weeks (EI4 or SI4) of healing or to sham groups. Echocardiography was employed to detect left ventricular function and the infarct size. Additionally, the TUNEL technique was used to assess apoptosis and immunohistochemistry was used to quantitatively analyze the PPAR-α, TNF-α and NF-κB antigens in the infarcted and non-infarcted myocardium. MI-related mortality was higher in SI4 than in EI4 (25% vs 12%), without a difference in MI size. SI4 exhibited a lower shortening fraction than EI4 did (24% vs 35%) and a higher apoptosis/area rate (3.97±0.61 vs 1.90±1.82) in infarcted areas (both p=0.001). Immunohistochemistry also revealed higher TNF-α levels in SI1 than in EI1 (9.59 vs 4.09, p<0.001) in infarcted areas. In non-infarcted areas, EI4 showed higher levels of TNF-α and positive correlations between PPAR-α and NF-κB (r=0.75, p=0.02), in contrast to SI4 (r=0.05, p=0.87). CONCLUSION: Previously exercised animals had better long-term ventricular function post-MI, in addition to lower levels of local inflammatory markers and less myocardial apoptosis, which seemed to be related to the presence of PPAR-α.


Assuntos
Infarto do Miocárdio/metabolismo , PPAR alfa/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Apoptose/fisiologia , Feminino , Inflamação/metabolismo , Modelos Animais , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , NF-kappa B/metabolismo , PPAR alfa/análise , Distribuição Aleatória , Ratos Wistar , Tempo , Fator de Necrose Tumoral alfa/metabolismo , Ultrassonografia , Função Ventricular/fisiologia
11.
Clinics ; 71(3): 163-168, Mar. 2016. tab, graf
Artigo em Inglês | LILACS | ID: lil-778995

RESUMO

OBJECTIVE: Exercise is a protective factor for cardiovascular morbidity and mortality, with unclear mechanisms. Changing the myocardial metabolism causes harmful consequences for heart function and exercise contributes to metabolic adjustment modulation. Peroxisome proliferator-activated receptors (PPARs) are also myocardium metabolism regulators capable of decreasing the inflammatory response. We hypothesized that PPAR-α is involved in the beneficial effects of previous exercise on myocardial infarction (MI) and cardiac function, changing the expression of metabolic and inflammatory response regulators and reducing myocardial apoptosis, which partially explains the better outcome. METHODS AND RESULTS: Exercised rats engaged in swimming sessions for 60 min/day, 5 days/week, for 8 weeks. Both the exercised rats and sedentary rats were randomized to MI surgery and followed for 1 week (EI1 or SI1) or 4 weeks (EI4 or SI4) of healing or to sham groups. Echocardiography was employed to detect left ventricular function and the infarct size. Additionally, the TUNEL technique was used to assess apoptosis and immunohistochemistry was used to quantitatively analyze the PPAR-α, TNF-α and NF-κB antigens in the infarcted and non-infarcted myocardium. MI-related mortality was higher in SI4 than in EI4 (25% vs 12%), without a difference in MI size. SI4 exhibited a lower shortening fraction than EI4 did (24% vs 35%) and a higher apoptosis/area rate (3.97±0.61 vs 1.90±1.82) in infarcted areas (both p=0.001). Immunohistochemistry also revealed higher TNF-α levels in SI1 than in EI1 (9.59 vs 4.09, p<0.001) in infarcted areas. In non-infarcted areas, EI4 showed higher levels of TNF-α and positive correlations between PPAR-α and NF-κB (r=0.75, p=0.02), in contrast to SI4 (r=0.05, p=0.87). CONCLUSION: Previously exercised animals had better long-term ventricular function post-MI, in addition to lower levels of local inflammatory markers and less myocardial apoptosis, which seemed to be related to the presence of PPAR-α.


Assuntos
Animais , Feminino , Infarto do Miocárdio/metabolismo , PPAR alfa/metabolismo , Condicionamento Físico Animal/fisiologia , Apoptose/fisiologia , Inflamação/metabolismo , Modelos Animais , Infarto do Miocárdio/patologia , Infarto do Miocárdio , NF-kappa B/metabolismo , PPAR alfa/análise , Distribuição Aleatória , Ratos Wistar , Tempo , Fator de Necrose Tumoral alfa/metabolismo , Função Ventricular/fisiologia
12.
In. Kalil Filho, Roberto; Fuster, Valetim; Albuquerque, Cícero Piva de. Medicina cardiovascular reduzindo o impacto das doenças / Cardiovascular medicine reducing the impact of diseases. São Paulo, Atheneu, 2016. p.73-88.
Monografia em Português | LILACS | ID: biblio-971529
13.
Work ; 52(2): 441-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26409373

RESUMO

BACKGROUND: Studies on the relationship between physical activity (PA) and being overweight/obese are inconclusive. OBJECTIVE: The purpose of this study was to examine the prevalence of excess body weight (EBW) and its association with daily PA level in a sample of 1506 Brazilian teachers. METHODS: The PA level was analyzed with the International Physical Activity Questionnaire and EBW was categorized as a body mass index (BMI) ≥25 kg/m2 and called 'overweight'. Chi-squared test and odds ratios (OR) were applied in the analysis. RESULTS: The prevalence of persons who were overweight was lower as a function of higher PA levels and higher PA levels resulted in a lower prevalence of overweight for men and women, respectively. The authors found that for men, moderate (OR: 1.69; P = 0.03) and high (OR: 2.57; P = 0.002) PA levels were predictive for being in the normal body mass index (BMI) range. In women, a greater association of being in the normal BMI range was reported only for a moderate PA level (OR: 1.43; P = 0.004). CONCLUSIONS: Higher daily PA levels are associated with being in the normal BMI range. To date, these findings will have important public health implications for an effective plan for the prevention of weight gain in Brazilian teachers.


Assuntos
Índice de Massa Corporal , Exercício/fisiologia , Sobrepeso/epidemiologia , Professores Escolares/estatística & dados numéricos , Adulto , Brasil/epidemiologia , Feminino , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Prevalência
14.
Circ Heart Fail ; 6(5): 1029-38, 2013 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-23894014

RESUMO

BACKGROUND: The present study addresses the hypothesis that the activity of dipeptidyl peptidase IV (DPPIV), an enzyme that inactivates peptides that possess cardioprotective actions, correlates with adverse outcomes in heart failure (HF). The therapeutic potential of DPPIV inhibition in preventing cardiac dysfunction is also investigated. METHODS AND RESULTS: Measurements of DPPIV activity in blood samples obtained from 190 patients with HF and 42 controls demonstrated that patients with HF exhibited an increase of ≈130% in circulating DPPIV activity compared with healthy subjects. Furthermore, an inverse correlation was observed between serum DPPIV activity and left ventricular (LV) ejection fraction in patients with HF. Similarly, radiofrequency LV ablation-induced HF rats displayed higher DPPIV activity in the plasma (≈50%) and heart tissue (≈3.5-fold) compared with sham-operated rats. Moreover, positive correlations were observed between the plasma DPPIV activity and LV end-diastolic pressure and lung congestion. Two days after surgery, 1 group of LV ablation-induced HF rats was treated with the DPPIV inhibitor sitagliptin (40 mg/kg BID) for 6 weeks, whereas the remaining rats were administered water. Hemodynamic measurements demonstrated that radiofrequency LV-ablated rats treated with sitagliptin exhibited a significant attenuation of HF-related cardiac dysfunction, including LV end-diastolic pressure, systolic performance, and chamber stiffness. Sitagliptin treatment also attenuated cardiac remodeling and cardiomyocyte apoptosis and minimized pulmonary congestion. CONCLUSIONS: Collectively, the results presented herein associate circulating DPPIV activity with poorer cardiovascular outcomes in human and experimental HF. Moreover, the results demonstrate that long-term DPPIV inhibition mitigates the development and progression of HF in rats.


Assuntos
Dipeptidil Peptidase 4/sangue , Insuficiência Cardíaca/enzimologia , Miocárdio/enzimologia , Adulto , Idoso , Animais , Apoptose , Biomarcadores/sangue , Estudos de Casos e Controles , Inibidores da Dipeptidil Peptidase IV/farmacologia , Modelos Animais de Doenças , Feminino , Peptídeo 1 Semelhante ao Glucagon/sangue , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Peptídeo Natriurético Encefálico/sangue , Edema Pulmonar/enzimologia , Edema Pulmonar/prevenção & controle , Pirazinas/farmacologia , Ratos , Ratos Wistar , Fosfato de Sitagliptina , Triazóis/farmacologia , Regulação para Cima , Função Ventricular Esquerda , Remodelação Ventricular
15.
Int J Cardiol ; 167(2): 357-61, 2013 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-22285448

RESUMO

BACKGROUND: The aim of the present study was to evaluate if the influence of digitalis on survival depends on the severity of cardiac dysfunction in heart failure (HF). METHODS AND RESULTS: Doppler echocardiogram (DE) parameters were analyzed in 84 Wistar control (C) and 80 Wistar rats treated with 0.1mg/100g/day of digitoxin (D) five days after coronary occlusion. The DE variables correlated with the survival of the animals were: myocardial infarction size, left chamber dimensions, fractional area change and E/A ratio. The animals were observed for up to 280 days. Mortality was worsened in rats in the D group with a myocardial infarction (MI)<37% and with better DE predictors of survival. Digitoxin was found to prolong survival in rats with an MI ≥ 37% and worse DE predictors. CONCLUSION: For the first time our study has shown experimentally that the action of digitalis glycosides can positively or negatively influence survival during treatment of HF. It prolongs survival of those in advanced state and compromises survival when there is less severity of the disease. In fact, the greater benefits occur when digitoxin was used in heightened ventricular dilatations and worse ventricular performance.


Assuntos
Digitoxina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/mortalidade , Índice de Gravidade de Doença , Animais , Digitalis , Feminino , Insuficiência Cardíaca/patologia , Infarto do Miocárdio/patologia , Ratos , Ratos Wistar , Taxa de Sobrevida/tendências
16.
Am J Physiol Regul Integr Comp Physiol ; 302(1): R166-74, 2012 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-22031782

RESUMO

Heart failure (HF) is associated with a reduced effective circulating volume that drives sodium and water retention and extracellular volume expansion. We therefore hypothesized that Na(+)/H(+) exchanger isoform 3 (NHE3), the major apical transcellular pathway for sodium reabsorption in the proximal tubule, is upregulated in an experimental model of HF. HF was induced in male rats by left ventricle radiofrequency ablation. Sham-operated rats (sham) were used as controls. At 6 wk after surgery, HF rats exhibited cardiac dysfunction with a dramatic increase in left ventricular end-diastolic pressure. By means of stationary in vivo microperfusion and pH-dependent sodium uptake, we demonstrated that NHE3 transport activity was significantly higher in the proximal tubule of HF compared with sham rats. Increased NHE3 activity was paralleled by increased renal cortical NHE3 expression at both protein and mRNA levels. In addition, the baseline PKA-dependent NHE3 phosphorylation at serine 552 was reduced in renal cortical membranes of rats with HF. Collectively, these results suggest that NHE3 is upregulated in the proximal tubule of HF rats by transcriptional, translational, and posttranslational mechanisms. Enhanced NHE3-mediated sodium reabsorption in the proximal tubule may contribute to extracellular volume expansion and edema, the hallmark feature of HF. Moreover, our study emphasizes the importance of undertaking a cardiorenal approach to contain progression of cardiac disease.


Assuntos
Insuficiência Cardíaca/metabolismo , Túbulos Renais Proximais/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , Animais , Transporte Biológico , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Modelos Animais de Doenças , Insuficiência Cardíaca/fisiopatologia , Túbulos Renais Proximais/fisiopatologia , Masculino , Modelos Animais , Fosforilação , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Trocador 3 de Sódio-Hidrogênio
17.
Clinics (Sao Paulo) ; 66(5): 889-93, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21789396

RESUMO

OBJECTIVE: This study aimed to investigate whether previous exercise training could prevent or attenuate acute cardiac alterations after myocardial infarction. METHODS: Female rats were submitted to swim training (1 h/day; 5 days/week) or allowed to remain sedentary for 8 weeks. Afterwards, they were randomly assigned to left coronary artery occlusion or sham surgery. After this procedure, the rats remained sedentary for one week until euthanasia. Cardiac structural and functional analyses were performed using Doppler echocardiography. The rats that had a moderate or large infarct size were included in the evaluations. The data (mean ± SEM) were analyzed using a two-way ANOVA model followed by Tukey's post-hoc test. RESULTS: After the surgery, no significant difference between the exercise and sedentary groups was observed in the left ventricular infarct sizes (34.58 ± 3.04 vs. 37.59 ± 3.07). In another group of rats evaluated with Evans blue 1 h after myocardial infarction, no siginificant difference in the area at risk was observed between the exercised and sedentary rats (49.73 ± 1.52 vs. 45.48 ± 3.49). The changes in the left ventricular fractional areas for the exercised and sedentary myocardial infarction groups (36 ± 2% and 39 ± 3%, respectively) were smaller than those for the exercise sham surgery (ES, 67 ± 1%) and sedentary sham surgery (SS, 69 ± 2%) groups. The E/A was higher in the sedentary myocardial infarction (4.4 ± 0.3) and exercised myocardial infarction (5.5 ± 0.3) rats than in the SS (2.4 ± 0.1) and ES (2.2 ± 0.1) rats. CONCLUSION: Previous swim training of female rats does not attenuate systolic and diastolic function alterations after myocardial infarction induced by left coronary artery occlusion, suggesting that cardioprotection cannot be provided by exercise training in this experimental model.


Assuntos
Infarto do Miocárdio/fisiopatologia , Condicionamento Físico Animal/fisiologia , Natação/fisiologia , Disfunção Ventricular/fisiopatologia , Animais , Estenose Coronária/fisiopatologia , Feminino , Infarto do Miocárdio/patologia , Distribuição Aleatória , Ratos , Ratos Wistar
18.
Clinics ; 66(5): 889-893, 2011. ilus, graf, tab
Artigo em Inglês | LILACS | ID: lil-593856

RESUMO

OBJECTIVE: This study aimed to investigate whether previous exercise training could prevent or attenuate acute cardiac alterations after myocardial infarction. METHODS: Female rats were submitted to swim training (1 h/day; 5 days/week) or allowed to remain sedentary for 8 weeks. Afterwards, they were randomly assigned to left coronary artery occlusion or sham surgery. After this procedure, the rats remained sedentary for one week until euthanasia. Cardiac structural and functional analyses were performed using Doppler echocardiography. The rats that had a moderate or large infarct size were included in the evaluations. The data (mean + SEM) were analyzed using a two-way ANOVA model followed byTukey's post-hoc test. RESULTS: After the surgery, no significant difference between the exercise and sedentary groups was observed in the left ventricular infarct sizes (34.58 + 3.04 vs. 37.59 + 3.07). In another group of rats evaluated with Evans blue 1 h after myocardial infarction, no siginificant difference in the area at risk was observed between the exercised and sedentary rats (49.73 + 1.52 vs. 45.48 + 3.49). The changes in the left ventricular fractional areas for the exercised and sedentary myocardial infarction groups (36 + 2 percent and 39 + 3 percent, respectively) were smaller than those for the exercise sham surgery (ES, 67+1 percent) and sedentary sham surgery (SS, 69 + 2 percent) groups. The E/A was higher in the sedentary myocardial infarction (4.4 + 0.3) and exercised myocardial infarction (5.5 + 0.3) rats than in the SS (2.4 + 0.1) and ES (2.2 + 0.1) rats. CONCLUSION: Previous swim training of female rats does not attenuate systolic and diastolic function alterations after myocardial infarction induced by left coronary artery occlusion, suggesting that cardioprotection cannot be provided by exercise training in this experimental model.


Assuntos
Animais , Feminino , Ratos , Infarto do Miocárdio/fisiopatologia , Condicionamento Físico Animal/fisiologia , Natação/fisiologia , Disfunção Ventricular/fisiopatologia , Estenose Coronária/fisiopatologia , Infarto do Miocárdio/patologia , Distribuição Aleatória , Ratos Wistar
19.
PLoS One ; 5(8): e12077, 2010 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-20711471

RESUMO

BACKGROUND: Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs) with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI). METHODOLOGY/PRINCIPAL FINDINGS: 99mTc-labeled ASCs (1x10(6) cells) isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C), or culture medium (ASC/M) as vehicle, and cell body distribution was assessed 24 hours later by gamma-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8+/-2.0 and 26.8+/-2.4% vs. 4.8+/-0.7%, respectively). Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV) perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT) and control groups (culture medium, fibrin, or collagen alone). Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV) and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW), a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. CONCLUSIONS: We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administering co-injection of ASCs with biopolymers.


Assuntos
Tecido Adiposo/citologia , Biopolímeros/farmacologia , Coração/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/cirurgia , Transplante de Células-Tronco , Células-Tronco/metabolismo , Animais , Biopolímeros/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Colágeno/administração & dosagem , Colágeno/farmacologia , Feminino , Fibrina/administração & dosagem , Fibrina/farmacologia , Coração/efeitos dos fármacos , Injeções , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Ratos , Ratos Endogâmicos Lew , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos
20.
Can J Physiol Pharmacol ; 88(7): 724-32, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20651820

RESUMO

After myocardial infarction, the hemodynamics under basal conditions might appear to be unaltered, which makes it difficult to identify cardiac dysfunction by the usual approaches. Thus, we tested the response to sudden afterload stress in infarcted rats with apparently normal ejection function. Control (CT) and infarcted (MI) Wistar rats with various MI sizes were submitted to echocardiography 30 days after coronary occlusion, followed by assessment of hemodynamics under basal conditions and during a pharmacologically induced sudden pressure overload (phenylephrine 15-25 microg/kg, i.v.). Coronary occlusion resulted in cardiac remodeling proportional to MI size, although several functional parameters such as systolic pressure (SP), stroke volume (SV), and stroke work (SW) of all MI rats were similar to those of CT rats. However, the afterload stress that was produced led to a relative preservation of SV and an increase of SW in CT rats; MI rats exhibited a significant reduction in SV and SW generation, although global cardiac function was normal under basal conditions, as indicated by regular echocardiography and hemodynamics assessment. Thus, we propose the use of sudden pharmacologically induced afterload stress as a practical and efficient procedure for identifying impaired performance of the heart in anesthetized rats, providing an additional physiological variable to be evaluated in experimental therapeutic studies.


Assuntos
Ecocardiografia sob Estresse/métodos , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Animais , Insuficiência Cardíaca/patologia , Hemodinâmica , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Fenilefrina , Ratos , Ratos Wistar , Função Ventricular Esquerda , Remodelação Ventricular
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