Clofibrate Treatment Decreases Inflammation and Reverses Myocardial Infarction-Induced Remodelation in a Rodent Experimental Model.

Myocardial infarction (MI) initiates an inflammatory response that promotes both beneficial and deleterious effects. The early response helps the myocardium to remove damaged tissue; however, a prolonged later response brings cardiac remodeling characterized by functional, metabolic, and structural pathological changes. Current pharmacological treatments have failed to reverse ischemic-induced cardiac damage. Therefore, our aim was to study if clofibrate treatment was capable of decreasing inflammation and apoptosis, and reverse ventricular remodeling and MI-induced functional damage. Male Wistar rats were assigned to (1) Sham coronary artery ligation (Sham) or (2) Coronary artery ligation (MI). Seven days post-MI, animals were further divided to receive vehicle (V) or clofibrate (100 mg/kg, C) for 7 days. The expression of IL-6, TNF-α, and inflammatory related molecules ICAM-1, VCAM-1, MMP-2 and -9, nuclear NF-kB, and iNOS, were elevated in MI-V. These inflammatory biomarkers decreased in MI-C. Also, apoptotic proteins (Bax and pBad) were elevated in MI-V, while clofibrate augmented anti-apoptotic proteins (Bcl-2 and 14-3-3ε). Clofibrate also protected MI-induced changes in ultra-structure. The ex vivo evaluation of myocardial functioning showed that left ventricular pressure and mechanical work decreased in infarcted rats; clofibrate treatment raised those parameters to control values. Echocardiogram showed that clofibrate partially reduced LV dilation. In conclusion, clofibrate decreases cardiac remodeling, decreases inflammatory molecules, and partly preserves myocardial diameters.

Cardioprotection by curcumin post-treatment in rats with established chronic kidney disease.

PURPOSE: The pathogenic mechanisms leading to cardiovascular disorders in patients with chronic kidney disease have not been clearly established, although increased oxidative stress has been pointed out as a potential cause. Therefore, as cardiovascular events are still the first cause of death in patients with chronic kidney disease and traditional drugs or therapies rarely have effects on cardiac complications, we sought to determine the effect of curcumin in treating cardiac dysfunction in rats with established chronic renal disease. METHODS AND RESULTS: Treatment consisted in daily administration of curcumin (120 mg/kg/day) dissolved in 0.05% carboxymethylcellulose via oral gavages during 30 days, beginning from day 30 after 5/6 nephrectomy (5/6Nx). Cardiac function, markers of oxidative stress, activation of PI3K/Akt/GSK3ß and MEK1/2-ERK1/2 pathway, metalloproteinase-II (MMP-2) content, overall gelatinolytic activity, ROS production and mitochondrial integrity were evaluated after 1-month treatment. Curcumin restored systolic blood pressure, diminished interventricular and rear wall thickening, decreased left ventricle dimension at end-systole (LVSd) and restored ejection fraction in nephrectomized rats. Also, it diminished metalloproteinase-II levels and overall gelatinase activity, decreased oxidative stress and inhibited the mitochondrial permeability transition pore opening. CONCLUSION: Our findings suggest that curcumin might have therapeutic potential in treatment of heart disease in patients with established CKD by attenuating oxidative stress-related events as cardiac remodeling, mitochondrial dysfunction and cell death.

Curcumin maintains cardiac and mitochondrial function in chronic kidney disease.

Curcumin, a natural pigment with antioxidant activity obtained from turmeric and largely used in traditional medicine, is currently being studied in the chemoprevention of several diseases for its pleiotropic effects and nontoxicity. In chronic renal failure, the pathogenic mechanisms leading to cardiovascular disorders have been associated with increased oxidative stress, a process inevitably linked with mitochondrial dysfunction. Thus, in this study we aimed at investigating if curcumin pretreatment exerts cardioprotective effects in a rat model of subtotal nephrectomy (5/6Nx) and its impact on mitochondrial homeostasis. Curcumin was orally administered (120mg/kg) to Wistar rats 7 days before nephrectomy and after surgery for 60 days (5/6Nx+curc). Renal dysfunction was detected a few days after nephrectomy, whereas changes in cardiac function were observed until the end of the protocol. Our results indicate that curcumin treatment protects against pathological remodeling, diminishes ischemic events, and preserves cardiac function in uremic rats. Cardioprotection was related to diminished reactive oxygen species production, decreased oxidative stress markers, increased antioxidant response, and diminution of active metalloproteinase-2. We also observed that curcumin's cardioprotective effects were related to maintaining mitochondrial function. Aconitase activity was significantly higher in the 5/6Nx + curc (408.5±68.7nmol/min/mg protein) than in the 5/6Nx group (104.4±52.3nmol/min/mg protein, P<0.05), and mitochondria from curcumin-treated rats showed enhanced oxidative phosphorylation capacities with both NADH-linked substrates and succinate plus rotenone (3.6±1 vs 1.1±0.9 and 3.1±0.7 vs 1.2±0.8, respectively, P<0.05). The mechanisms involved in cardioprotection included both direct antioxidant effects and indirect strategies that could be related to protein kinase C-activated downstream signaling.

[Echocardiographic assessment of ventricular synchrony. Implications to patient selection and treatment outcome]. / Evaluación ecocardiográfica de la sincronía ventricular. Implicaciones en la selección de pacientes y en los resultados del tratamiento.

Heart failure is one of the most prevalent diseases in industrialized countries. Up to 30% of the patients with advanced heart failure present disturbances in intra-ventricular conduction, and this produce asynchrony of ventricular contractility, leading to further deterioration in heart function. Cardiac resynchronization (TRC) is an increasingly important therapeutic option for a subgroup of patients with heart failure. Several methods have been show to be useful in study the mechanical asynchrony. However, there are discrepancies between the results of the different methods. The echocardiography provides the best parameters in predicting a good response.

[Acute right atrial and ventricular infarction]. / Infarto agudo de aurícula y ventrículo derechos.

Acute coronary syndromes involving the right side of the heart are associated with increased mortality, a complex clinical course, and lengthy hospitalization, as well as with frequent mechanical and electrical complications. It is important that the signs and symptoms associated with the spread of ischemic disease to the right heart chambers are recognized so that the patient can be given appropriate treatment, which can improve short-term and long-term prognosis. The purpose of this review was to summarize key aspects of the diagnosis, prognosis and treatment of this condition.

Infarto agudo de aurícula y ventrículo derechos / Acute right atrial and ventricular infarction

Los síndromes coronarios agudos que involucran a la parte derecha del corazón se acompañan de una elevada mortalidad, una compleja evolución clínica y un prolongado tiempo de hospitalización, así como de complicaciones mecánicas y eléctricas frecuentes. Es importante reconocer los signos y los síntomas relacionados con la extensión del proceso isquémico a las cavidades derechas, lo cual permite aplicar un tratamiento adecuado que mejora el pronóstico a corto y largo plazo. En esta revisión pretendemos incluir los aspectos más relevantes relacionados con el diagnóstico, el pronóstico y el tratamiento de esta enfermedad

Acute coronary syndromes involving the right side of the heart are associated with increased mortality, a complex clinical course, and lengthy hospitalization, as well as with frequent mechanical and electrical complications. It is important that the signs and symptoms associated with the spread of ischemic disease to the right heart chambers are recognized so that the patient can be given appropriate treatment, which can improve short-term and long-term prognosis. The purpose of this review was to summarize key aspects of the diagnosis, prognosis and treatment of this condition