Metabolism of hibernating myocardium and regulation of uncoupling protein 2 / 中国药理学通报

HM(hibernating myocardium)is an adaptive phenome-non of myocardium against sustained ischemia,which maintains its tissue vitality through balancing energy supply and demand.It widely exists in patients suffering from coronary heart disease. HMhas its own metabolic pattern,instead of regular FAO(fatty acid β-oxidation)-based metabolism,glycolysis became main pro-cedure.Reduction of FAO,TCA (tricarboxylic cacidcycle),ETC (electron transport chain)enzyme has been observed,ROS(reac-tive oxygen species)and UCP2(uncoupling protein 2)have been up-regulated.UCP2,which promotes proton leak across innermembrane of mitochondrial and leads to ATP reduction,has e-merged as an important regulator of the energy production.It is regulated by up-stream proteins such as AMPK,PPARs,PGC-1α,and other factors like FFA(free fat acid),ROS and purine nucleotide.HM has potential function of ischemic myocardium, which can improve cardiac function through reasonable interven-tion.Modulation of UCP2 can optimize energy production,and is essential to HM metabolism.

Moderate physical training counterbalances harmful effects of low-protein diet on heart: metabolic, oxidative and morphological parameters

Aims: Maternal low-protein diet induces several impairments on cardiac system. Conversely, moderate exercise has been widely recommended to health improvement due to its effects on heart function. Thus, we investigated whether the moderate physical training is capable to offset the lasting injuries of a maternal protein restriction on the hearts of male adult rats. Methods: Pregnant rats were divided into two groups: Control (C=17% casein) and undernutrition (U=8% casein). Offspring from the undernutrition group, at 60 days of life, were subdivided into undernutrition (U) and undernutrition+exercise (UT) groups. Treadmill exercise was performed: (8 weeks, 5 days/week, 60 min/day at 70% of VO2máx). 48 hours after last exercise session, tissues were collected for morphological and biochemical analysis. Results Despite the deleterious effect induced by low-protein diet, physical training was able to restore morphological parameters to similar levels to the control group. Additionally, oxidative stress index was also improved in UT group, due to the increase in antioxidant enzymatic defense. In metabolic enzymes, maternal low-protein diet induced a change in metabolism, and moderate physical training improved oxidative metabolism. Conclusion: We demonstrated that moderate physical training can offset the cardiac metabolism in adult rats that were exposed to a maternal low-protein diet.(AU)

Combined effects of age and diet-induced obesity on biochemical parameters and cardiac energy metabolism in rats.

Obesity is often associated with decreased fat oxidation and aging is a well-recognized risk factor for cardiovascular disease. This study investigated calorimetric and morphometric parameters, as well as the glucose levels, lipid profile and cardiac energy metabolism in young and old, controls and obese rats. The animals were divided into four groups: Group I (GI): young rats fed normal diet for 75 days; Group II (GII): young rats fed hypercaloric diet (HD) for 75 days; Group III (GIII): old rats fed normal diet for 510 days; and Group IV (G IV): old rats fed HD for 510 days. The following analyses were performed: calorimetric, glucose and lipid concentrations, atherogenic index (AI), total antioxidant substances (TAS), fat depots, cardiac lipid hydroperoxide (LH) and cardiac lactate dehydrogenase (LDH), citrate synthase (CS), phosphofructokinase (PFK) and pyruvate dehydrogenase (PDH) activities. Older animals were heavier than young and the hypercaloric animals were heavier than controls. Animals from GIV had lower fat oxidation than GIII, which in turn, had higher fat oxidation than GI. Total cholesterol, LDL-C and all fat depots were higher in the GII, as compared to GI. The GIV rats had higher VLDL, retroperitoneal fat, serum lipids and cardiac glycogen levels than GII. Furthermore, GIV rats had higher fat depots, triacylglycerol, total cholesterol and VLDL than GIII. Animals from GII and -IV showed higher LH and AI than age-matched controls. Older hypercaloric rats also had higher TAS than older control rats, which also had lower LH and TAS than younger control rats. Aged animals had increased CS and LDH and decreased PFK and PDH activities. Additionally, GIV rats exhibited an increase in PDH activity, compared to GIII. We conclude that the consumption of HD coupled with aging leads to impaired basal and cardiac metabolism.

Malondialdeído e troponina I cardíaca em equinos da raça Puro Sangue Árabe submetidos ao exercício e à suplementação com vitamina E / Malondialdehyde and cardiac troponin I in Arabian horses subjected to exercise and vitamin E supplementation

Para avaliar o efeito do exercício físico, do treinamento e da suplementação com vitamina E sobre o malondialdeído (MDA) e a troponina I cardíaca (cTnI) séricos, foram utilizados 16 equinos da raça Puro Sangue Árabe, sem treinamento, divididos em dois grupos de oito: controle e suplementado com vitamina E. Ambos os grupos foram submetidos a provas de exercício progressivo em esteira de alta velocidade inclinada a +7 por cento, antes (P1) e após (P2) o período de treinamento de 20 dias. Foram determinadas as concentrações séricas de MDA, vitamina E e cTnI e realizou-se o eletrocardiograma de repouso antes e após as provas P1 e P2. Os resultados sugerem a ocorrência do estresse oxidativo ocasionado pelo exercício, determinado por meio do aumento de MDA sérico. Em alguns animais, houve um discreto aumento de cTnI associado à detecção de complexos ventriculares prematuros, mas que não representou lesão cardíaca expressiva. Não houve efeito do treinamento sobre o estresse oxidativo. Portanto, é possível concluir que o exercício físico progressivo promoveu a lipoperoxidação nessas condições, que não foi prevenida pela suplementação com vitamina E nem pelo treinamento, mas não foi suficiente para causar uma lesão cardíaca significativa.

To evaluate the effect of exercise, training and vitamin E supplementation on serum malondialdehyde (MDA) and cardiac troponin I (cTnI), sixteen adult untrained Arabian horses were divided into 2 groups of 8 animals each, control and supplemented with vitamin E. Both groups had incremental exercise tests performed on a high-speed treadmill at a +7 percent slope, before (P1) and after (P2) a training period of 20 days. Serum concentrations of MDA, vitamin E and cTnI, and resting electrocardiogram were performed before and after P1 and P2. Results suggested that oxidative stress was induced by exercise as measured by serum MDA increase. In some animals, there was a subtle increase in cTnI concentration associated with the detection of ventricular premature complexes, which didn't represent a significant cardiac injury. There was no training effect on oxidative stress. It was concluded that, under the conditions above, the incremental exercise promoted lipoperoxidation, which was not prevented by vitamin E supplementation or training, however, it was not enough to cause a significant cardiac damage.

Medición del metabolismo de la glucosa en pacientes con miocardiopatía dilatada mediante tomografía de emisión de positrones con 18F-FDG: experiencia inicial / Measurement of glucose metabolism in patients with dilated cardiomyopathy by 18F-FDG PET

Introducción. La Fluor-18 deoxiglucosa (18F-FDG) ha sido utilizada en múltiples estudios para determinar la tasa de utilización de la glucosa en condiciones normales y patológicas. Actualmente se sabe que en la insuficiencia cardiaca el patrón metabólico se encuentra alterado. Materiales y métodos Se realizó medición del metabolismo glucocídico en 4 portadores de miocardiopatía dilatada y en 3 sujetos sanos, todos bajo una carga de hidratos de carbono vía oral (75gr). Se adquirieron imágenes dinámicas de tórax. La captación miocárdica se estimó a partir de las curvas tiempo-actividad en aurícula y ventrículo izquierdo utilizando el análisis gráfico de Patlak. Resultados. Los siete pacientes estudiados son de sexo masculino. La tasa de captación de la 18F-FDG para el grupo de pacientes con miocardiopatía dilatada fue 1,31 +/- 0,2 versus 1,26 +/- 0,37 ml/100gr/min en el grupo control. Conclusión. La medición del metabolismo cardiaco de la glucosa por medio de 18F-FDG PET es posible de realizar en un servicio clínico, permitiendo de esta forma determinar la repercusión fisiológica y los cambios del metabolismo miocárdico en diversas enfermedades además de la evaluación de terapia.

Introduction. Fluorine18 deoxyglucose (18F-FDG) has been used in numerous studies to determine the cardiac rate of glucose metabolism in normal and pathological conditions. It is known that during heart failure the metabolic pattern is altered. Patlack’s graphical analysis allows the assessment of heart muscle glucose consumption in patients with non-ischaemic heart failure and normal subjects. Methods. Standardized measurement of glucose metabolism was performed in four patients with dilated cardiomyopathy and three healthy subjects. All subjects received an oral load of carbohydrates (75gr) previous to scanning. Dynamic images of the thorax were acquired. Myocardial uptake was estimated from time-activity curves in the atrium and left ventricle using Patlack’s graphical analysis. Results. All subjects studied were male. 18F-FDG uptake rate for the group with dilated cardiomyopathy was 1.31 +/-0.2, versus 1.26 +/- 0.37 ml/100gr/min in the control group. Conclusion. Measurement of cardiac glucose metabolism by 18F-FDG PET is feasible in a clinical service, allowing impact evaluation of physiologic and metabolic changes in the myocardium in different pathologic scenarios in addition to therapy assessment.

Tomografía por emisión de positrones (PET): Una herramienta útil para el estudio del metabolismo cardiaco / Positron emission tomography (PET): A useful tool for the assessment of cardiac metabolism

En condiciones normales el metabolismo energético del corazón se basa en la oxidación de ácidos grasos y en menor proporción de carbohidratos. La función cardiaca depende del suplemento adecuado de trifosfato de adenosina (ATP) proveniente de dichos sustratos. Sin embargo, la fuente principal de energía está sujeta a modificación porfactorestanto fisiológicos (ejercicio) como patológicos (isquemia-reperfusión). Recientemente, se ha puesto gran atención al papel de la carnitina como regulador del metabolismo de ácidos grasos y carbohidratos mediante la modulación de la relación intramitocondrial de acetil-CoA/CoA. Las alteraciones en el metabolismo de carbohidratos y ácidos grasos a nivel miocárdico se han asociado al desarrollo de diversas patologías cardiovasculares (cardiopatía isquémica, hipertrofia ventricular, y miocardiopatía dilatada) por lo cual el estudio del metabolismo cardiaco cobra gran relevancia para el diagnóstico, y pronóstico de estas patologías. Dentro de la práctica clínica, la tomografía por emisión de positrones (PET) es una de las técnicas más empleadas para la evaluación del metabolismo cardiaco. Los radiotrazadores más ampliamente empleados en imagen PET son "C-palmitato, "C-acetato y 18Fluoro-2-desoxiglucosa (FDG), los dos primeros se emplean para el estudio del metabolismo oxidativo de los ácidos grasos y la FDG nos permite estudiar el metabolismo de carbohidratos.

Under normal conditions, myocardial metabolism is based on the oxidation of fatty acids and in a lesser extent carbohydrates. Cardiac function depends upon an adequate supplement of adenosine triphosphate(ATP) by these substrates. However, the main source of energy is susceptible to change upon a various physiologic (exercise) as well as pathologic (ischemia-reperfusion) conditions. Recently, carnitine has gained attention as a modulator of fatty acids and carbohydrates metabolism by means of modifying intramitochondrial Acetyl-CoA/CoA ratio. Disturbances in fatty acids and carbohydrates metabolism in the myocardium have been associated with cardiovascular diseases (chronic ischemic disease, ventricular hypertrophy and dilated cardiomyopathy). The evaluation of cardiac metabolism attains great value regarding diagnosis, treatment and prognosis of these diseases. Currently, positron emission tomography (PET) is one of the preferred methods to evaluate cardiac energy metabolism in clinical practice. In PET images the tracers most commonly used are "C-palmitate, "C-acetate y 18Fluoro-2-deoxyglucose (FDG), the first two are employed to assess fatty acids oxidation and FDG is used to evaluate carbohydrates metabolism.

Cambios en el metabolismo cardíaco y su posible aprovechamiento en la terapéutica (Parte II) / Chages in cardiaac metabolism and their possible use in therapeutics (prtt ii)

En esta segunda parte de nuestra revisión se propone a la solución polarizante como una alternativa más, además de otras ya existentes, para el mantenimiento de las células cardíacas durante un infarto, apoyado en el cambio metabólico cardíaco durante la hipoxia.

Based on the cardiac metabolic changes during hypoxia, in this second part of our review we propose, the polarizing solution as an alternative for the maintenance of the cardiac cells during an infarction, in conjunction with other alternative therapies.

Cambios en el metabolismo cardíaco y su posible aprovechamiento en la terapéutica (Parte I) / Changes in cardiac metabolism and their possible use in therapeutics (Part I)

El propósito de esta revisión es analizar las diferentes rutas metabólicas utilizadas por el corazón en momentos del desarrollo y situaciones como la hipoxia y la enfermedad, para tratar de comprenderlas y utilizarlas para restablecer las condiciones normales en células que se encuentran comprometidas durante un infarto.

We describe different metabolic states of the heart, during developmental stages, hypoxia and illness, to understand and use them to try to reestablish the normal conditions. (Arch Cardiol Mex 2003; 73:218-229).