Physical Training Improves Cardiac Structure and Function of Rats After Doxorubicin-Induced Cardiomyopathy

Abstract Background: The use of doxorubicin in chemotherapy has been associated with cardiotoxicity and heart failure. Physical exercise produces favorable morphofunctional adaptations in the cardiovascular system and may reverse cardiac dysfunction in patients undergoing chemotherapy. Objective: To assess the effects of physical training on myocardial structure, cardiac function, and exercise tolerance in Wistar rats initiated after the onset of cardiotoxicity-induced cardiotoxicity. Methods: This study investigated 30 adult male Wistar rats randomly divided into four groups: control (C), exercise (EX), doxorubicin (DX), and doxorubicin and exercise (DXEX). The DX and DXEX groups received six doses of doxorubincin from 1.25 mg/kg body weight up to a cumulative dose of 7.5 mg/kg. Injections were administered intraperitoneally three times a week for two weeks; after this stage, the EX and DXEX groups started physical training (swimming) sessions three times a week with a load of 5% of their body weight. Echocardiography and exercise tolerance tests were performed. Generalized linear models were used in statistical analysis, and a p<0.05 was set as statistically significant. Results: Left ventricular shortening fraction and ejection fraction were reduced in the DX group compared to C, EX, and DXEX. The DXEX group showed greater tolerance to effort when compared to the DX and C groups. Conclusion: Physical training, initiated after the onset of doxorubicin-induced cardiotoxicity, improved cardiac function and exercise tolerance in rats.

Impacto da drenagem linfática manual nos sintomas relacionados ao edema de membros inferiores de gestantes / Impacto del drenaje linfático manual sobre los síntomas relacionados con el edema de miembros inferiores en mujeres embarazadas / Impact of the manual lymphatic drainage on symptoms related to lower-extremity edema in pregnant women

RESUMO O objetivo deste artigo é analisar os efeitos da drenagem linfática manual sobre os sintomas de sensação de peso, dor, edema e formigamento nos membros inferiores de gestantes, assim como na redução da perimetria. A amostra foi composta por 23 voluntárias, e foram realizados 35 atendimentos. Foram incluídas gestantes com idade gestacional acima de 26 semanas, que apresentavam sensação de peso, dor, edema e formigamento nos membros inferiores, com autorização escrita do médico obstetra para que fossem submetidas a drenagem linfática manual utilizando o método Leduc. Foram excluídas gestantes que apresentaram pressão arterial superior a 140/100mmHg no momento da realização da drenagem linfática manual, lesão de continuidade da epiderme, doenças dermatológicas, linfáticas e cardíacas, infecções e varizes volumosas e/ou sintomáticas. As avaliações foram realizadas imediatamente após a aplicação da drenagem linfática manual e duas horas depois, por meio de questionário estruturado pelas pesquisadoras. Diferenças estatisticamente significativas foram encontradas antes, imediatamente após e após duas horas da intervenção no que se refere à melhora da dor (p=0,001*), do formigamento (p=0,01*), da sensação de peso (p=0,000*) e do inchaço (p=0,000*). Em relação à perimetria antes e após o tratamento, houve diminuição na maioria das mensurações realizadas. A técnica de drenagem linfática manual tem papel fundamental na melhora da qualidade de vida da gestante devido ao relaxamento e bem-estar proporcionado, componentes considerados essenciais para redução da ansiedade e com benefícios que podem perdurar até o parto.

RESUMEN El objetivo de este estudio es analizar los efectos del drenaje linfático manual sobre los síntomas de pesadez, dolor, edema y hormigueo en miembros inferiores de mujeres embarazadas, así como sobre la reducción de la perimetría. La muestra estuvo conformada por 23 voluntarias, y se realizaron 35 consultas. Se incluyeron a mujeres embarazadas con edad gestacional superior a 26 semanas, que presentaban sensación de pesadez, dolor, edema y hormigueo en miembros inferiores, y que habían sido autorizadas por el obstetra para someterse al drenaje linfático manual con el método Leduc. Se excluyeron a mujeres embarazadas con presión arterial superior a 140/100mmHg en el momento del drenaje linfático manual, lesión de continuidad de la epidermis, enfermedades dermatológicas, linfáticas y cardíacas, infecciones y varices grandes y/o sintomáticas. Las evaluaciones se realizaron tras aplicar el drenaje linfático manual y dos horas después, por medio de un cuestionario estructurado por las investigadoras. Se encontraron diferencias estadísticamente significativas antes, inmediatamente después y después de dos horas de la intervención en relación a la mejoría del dolor (p=0,001*), hormigueo (p=0,01*), sensación de pesadez (p=0,000*) e hinchazón (p=0,000*). La perimetría antes y después del tratamiento disminuyó en la mayoría de las mediciones realizadas. La técnica de drenaje linfático manual juega un papel fundamental en la mejora de la calidad de vida de mujeres embarazadas por provocar relajación y bienestar, componentes claves para reducir la ansiedad, con beneficios que pueden durar hasta el parto.

ABSTRACT This article aims to analyze the effects of manual lymphatic drainage on symptoms related to gestational edema in the lower limbs, such a sensation of heaviness, pain, swelling, and tingling, as well as on perimetry. The sample consisted of 23 pregnant women with gestational age above 26 weeks, who were submitted to 35 sessions of drainage based on Leduc's method upon the authorization of their physicians. Participants with blood pressure above 140/100 mmHg at the time of drainage and presenting with skin continuity wound, heart disease, dermatological disease, lymphatic disease, infections, and voluminous or symptomatic varicose veins were excluded from the study. Symptoms were evaluated immediately and two hours after drainage by means of questionnaires. Improvements in pain (p=0.001*), tingling (p=0.01*), sensation of heaviness (p=0.000*), and swelling (p=0.000*) showed statistically significant differences before, immediately after, and two hours after intervention. Most perimetry measurements also presented a decrease after treatment. The technique of manual lymphatic drainage is very important to provide well-being and a better quality of life in pregnant women. The benefits arising from such a method are essential to decrease anxiety, enduring up until childbirth.

Doxorubicin-induced Cardiotoxicity and Cardioprotective Agents: Classic and New Players in the Game.

Doxorubicin (DOX) is a cytostatic antibiotic from the class of anthracyclines widely used in chemotherapeutic cancer treatments. Despite the efficiency against several types of cancer, the use of DOX remains limited due to the side effects, especially cardiotoxicity. Among the DOX administration strategies, there are the "classic players" such as nanoparticles and polymers, which are capable of DOX delivery directly to interesting neoplastic regions. On the other hand, the "new players" such as phytochemicals and probiotics emerged with the proposal to react with DOX free radicals, reducing the oxidative stress, inflammatory and apoptotic process. Thus, this review aims to report the studies involving these classics and new players along the years that focus on improved administration and reduction of DOX-induced cardiotoxicity.

Activation of Both the Calpain and Ubiquitin-Proteasome Systems Contributes to Septic Cardiomyopathy through Dystrophin Loss/Disruption and mTOR Inhibition.

Cardiac dysfunction caused by the impairment of myocardial contractility has been recognized as an important factor contributing to the high mortality in sepsis. Calpain activation in the heart takes place in response to increased intracellular calcium influx resulting in proteolysis of structural and contractile proteins with subsequent myocardial dysfunction. The purpose of the present study was to test the hypothesis that increased levels of calpain in the septic heart leads to disruption of structural and contractile proteins and that administration of calpain inhibitor-1 (N-acetyl-leucinyl-leucinyl-norleucinal (ALLN)) after sepsis induced by cecal ligation and puncture prevents cardiac protein degradation. We also tested the hypothesis that calpain plays a role in the modulation of protein synthesis/degradation through the activation of proteasome-dependent proteolysis and inhibition of the mTOR pathway. Severe sepsis significantly increased heart calpain-1 levels and promoted ubiquitin and Pa28ß over-expression with a reduction in the mTOR levels. In addition, sepsis reduced the expression of structural proteins dystrophin and ß-dystroglycan as well as the contractile proteins actin and myosin. ALLN administration prevented sepsis-induced increases in calpain and ubiquitin levels in the heart, which resulted in decreased of structural and contractile proteins degradation and basal mTOR expression levels were re-established. Our results support the concept that increased calpain concentrations may be part of an important mechanism of sepsis-induced cardiac muscle proteolysis.

Análise histomorfométrica e funcional do miocárdio de ratos wistar submetidos ao esforço físico crônico / Histomorphometric and functional analysis of the myocardium of wistar rats submitted to chronic physical effort

O esforço físico crônico e conhecido por induzir uma serie de adaptações morfo-funcionais no sistema cardiovascular. As alterações funcionais podem ser observadas através do tempo médio de realização de um determinado protocolo de esforço físico com intensidade e duração pré-definidas ou não, como o de esforço físico exaustivo a 6% de sobrecarga corporal que foi utilizado neste estudo para avaliação funcional. Alem das alterações funcionais, modificações anatômicas cardíacas como um aumento na massa ventricular, podem ser observadas, dependendo dos padrões de intensidade, duração e freqüência do esforço físico crônico. Para analisar-se estas referidas alterações adaptativas, o esforço físico realizado em água por ratos e um bom modelo experimental. Este trabalho foi realizado com o objetivo de se analisar as possíveis respostas adaptativas decorrentes do esforço físico crônico breve, por quatro semanas, sob diferentes intensidades máximas, relativas as sobrecargas corpórea de 2%, 4% e 6%. Na analise morfométrica não houve alteração morfológica significativa em nenhum dos grupos estudados. Os resultados obtidos em função do esforço físico exaustivo indicaram um perfil adaptativo funcional do sistema cardiovascular significativo dos animais submetidos ao esforço físico crônico com sobrecarga máxima de 6 %.

Chronic physical effort is known for inducing a serie of morphofunctional adaptations at the cardiovascular system. The functional alterations can be observed through the average realization time of a determined physical effort protocol with pre-defined, or not, intensity and duration, with tone of exhaustive physical effort at 6% of body overcharge, which was used in this study for functional evaluation. Besides the functional alterations, heart anatomic alterations like increase of ventricular muscle mass, we can observe, depending on the intensity, duration and frequency patterns of chronic physical effort. The physical effort made by rats inside the water is a good experimental model to analyze these adaptive alterations. This study was realized with the intention of analyzing the possible adaptive answers resulting from brief chronic physical effort, for four weeks, under different maximum intensities, related to body overcharges of 2%, 4% and 6%. At the morphometric analysis there was no significant alteration in any of the studied groups. The results obtained due to the exhaustive physical effort indicated a significant adaptive functional profile of the cardiovascular system in animals submitted to chronic physical effort with maximum overload of 6%.