Moderate-intensity exercise allows enhanced protection against oxidative stress-induced cardiac dysfunction in spontaneously hypertensive rats

The progression of myocardial injury secondary to hypertension is a complex process related to a series of physiological and molecular factors including oxidative stress. This study aimed to investigate whether moderate-intensity exercise (MIE) could improve cardiac function and oxidative stress in spontaneously hypertensive rats (SHRs). Eight-week-old male SHRs and age-matched male Wistar-Kyoto rats were randomly assigned to exercise training (treadmill running at a speed of 20 m/min for 1 h continuously) or kept sedentary for 16 weeks. Cardiac function was monitored by polygraph; cardiac mitochondrial structure was observed by scanning electron microscope; tissue free radical production was measured using dihydroethidium staining. Expression levels of SIRT3 and SOD2 protein were measured by western blot, and cardiac antioxidants were assessed by assay kits. MIE improved the cardiac function of SHRs by decreasing left ventricular systolic pressure (LVSP), and first derivation of LVP (+LVdP/dtmax and −LVdP/dtmax). In addition, exercise-induced beneficial effects in SHRs were mediated by decreasing damage to myocardial mitochondrial morphology, decreasing production of reactive oxygen species, increasing glutathione level, decreasing oxidized glutathione level, increasing expression of SIRT3/SOD2, and increasing activity of superoxide dismutase. Exercise training in SHRs improved cardiac function by inhibiting hypertension-induced myocardial mitochondrial damage and attenuating oxidative stresses, offering new insights into prevention and treatment of hypertension.

Importancia clínica del estudio estructural y funcional de las mitocondrias en las diferentes miocardiopatías / Clinical significance of structural and functional study of mitochondria in different cardiomyopathies

Los principales mecanismos que intervienen en la génesis y progresión de la insuficiencia cardiaca no se encuentran aclarados totalmente. El presente estudio se llevó a cabo para analizar la participación de las mitocondrias en la insuficiencia cardíaca y el posible paralelismo que hubiere entre el músculo cardíaco y el músculo esquelético en relación a los síntomas clínicos y el daño mitocondrial. También se analizaron los factores de riesgo para enfermedad cardiovascular en los diferentes grupos de estudio, y como se vinculan con las alteraciones estructurales y funcionales de las mitocondrias; así como se estudiaron en un modelo experimental, las posibles modificaciones de las mitocondrias cardíacas y esqueléticas producidas por los distintos fármacos utilizados para el tratamiento de la insuficiencia cardíaca.Veintisiete (27) pacientes que se sometieron a cirugía cardiovascular por diferentes razones y aceptaron participar en este estudio se incluyeron.Los criterios de inclusión para el grupo de control (n = 6) fueron pacientes de ambos sexos con fracción de eyección ventricular izquierda normal (FEVI) (> 60%), sin enfermedad reumatológica, diabetes, hipertensión arterial, dislipemia, obstrucción de vasos coronarios, siendo la comunicación interauricular el diagnóstico único para la cirugía.

Abstract: The fundamental mechanisms involved in the genesis and progression of heart failure are not clearly understood. Present study was conducted to analyze the cardiac mitochondrial involvement in heart failure, the possible parallelism between cardiac and skeletal muscle and if there is a link between clinical symptoms and mitochondrial damage. The risk factors were also analyzed in the different groups under study and the possible modification upon cardiac and skeletal mitochondria produced by the different drugs used for cardiac failure treatment was also studied in an experimental model. Twenty seven patients who underwent cardiovascular surgery for different reasons and accepted to participate in this study were included.

Evaluation of the mitochondrial respiration of cardiac myocytes in rats submitted to mechanical bile duct obstruction / Avaliação da respiração mitocondrial de miócitos cardíacos em ratos ictéricos sumetidos à obstrução do ducto biliar

PURPOSE: The objective of the present study was to evaluate the capacity of the myocardium for energy production by the analysis of mitochondrial respiration in rats with jaundice submitted to bile duct ligature. METHODS: Sixteen male Wistar rats were divided into 2 Groups: Group SO submitted to nontherapeutic laparotomy (sham operation) and Group IC (icteric group) submitted to bile duct ligature. After 7 days, laparotomy was again performed in all animals for cardiac muscle extraction and analysis. Mitochondrial oxygen consumption was determined by stage 3 velocity and stage 4 velocity. The respiratory control ratio (RCR) was obtained by the ratio of stage 3 to stage 4 velocity. Statistical analysis was performed by the Mann-Whitney test, with the level of significance set at 5 percent (p<0.05). RESULTS: Statistical analysis revealed a significant drop in oxygen consumption during stage 3 mitochondrial respiration in group IC compared with SO, whereas the values obtained during stage 4 were basically identical for the two groups. Likewise, RCR values exhibited a significant reduction. CONCLUSION: The cellular respiration of the "jaundiced heart" is depressed. This was demonstrated by the reduced capacity of cardiac mitochondria to consume oxygen and synthesize ATP, supporting the idea of a latent cardiac impairment responsible for the hemodynamic decompensation occurring during cholestasis.

OBJETIVO: A proposta deste trabalho é avaliar a capacidade de produção energética do miocárdio mediante análise da respiração mitocondrial em ratos ictéricos submetidos à ligadura do ducto biliar. MÉTODOS: Foram utilizados 16 ratos Wistar machos divididos em 2 Grupos: Grupo SO , os quais foram submetidos à Laparotomia branca e Grupo IC, os quais sofreram ligadura do ducto biliar para o desenvolvimento de icterícia obstrutiva. Todos os animais após 7 dias de cirurgia foram submetidos à nova laparotomia para extração e análise do músculo cardíaco. O consumo de oxigênio pelas mitocôndrias foi determinado pela velocidade do estado 3 e velocidade do estado 4. A razão do controle respiratório (RCR) foi obtida pela relação entre as velocidades dos estados 3 e 4. A análise estatística foi feita pelo teste de Mann-Whitney com nível de significância de 5 por cento (p<0.05). RESULTADOS: Observou-se queda estatisticamente significante nos valores do consumo de oxigênio do estado 3 da respiração mitocondrial no grupo IC em relação ao SO, no entanto os valores para estado 4 permaneceram basicamente inalterados entre os grupos. Os valores de RCR entre os grupos também apresentaram diminuição significativa. CONCLUSÃO: A respiração celular do 'coração ictérico' está deprimida em decorrência da redução da capacidade da mitocôndria cardíaca em consumir oxigênio e sintetizar ATP, o que pode contribuir para a disfunção cardiovascular na vigência da colestase.

A method to estimate mitochondrial Ca2+ uptake in intact cardiac myocytes

In the present paper we describe a method to estimate mitochondrial Ca2+ uptake during the declining phase of Ca2+ transients (cell relaxation) in intact isolated myocardial cells. This method is based on inhibition of sarcoplasmic reticulum (SR) Ca2+ accumulation by caffeine, blockade of Ca2+ transport via sarcolemmal Ca2+ -ATPase by treatment with carboxyeosin and inhibition of sarcolemmal Na+/Ca+ exchange by removal of extracellular Na+ and Ca2+. Ca2+ transients were evoked in rabbit ventricular myocytes by quick and sustained caffeine application (10 mM) after a 5-min period of electrical stimulation to load the SR with Ca2+. Mitochondrial Ca2+ transport was estimated using a model described by Sipido and Wier (Journal of Physiology (1991), 435: 605-630), which was originally proposed to describe Ca2+ fluxes during excitation-contraction coupling in cardiac cells. Our results indicate that, in intact rabbit myocytes, the Ca2+ flux due to net mitochondrial CA2+ uptake may attain a value close to 1 muM/sec.

The heart of the icefish: bioconstruction and adaptation

The Channichthyidae or "icefish" represent an intriguing example of extreme adaptation to the stable low temperature and high oxygen content of the Antarctic waters. The lack of respiratory pigments (hemoglobin and myoglobin) in these teleosts is associated with relatively low oxygen consumption and relevant cardio-circulatory adjustments which include large blood volume, increased relative heart weight (cardiomegaly), and very high cardiac output. The heart has the ability to displace large systolic volumes at a low rate and relatively low pressure, with large ventricular fillings (high ventricular compliance), whereas it is incapable of facing increased afterloads. These functional aspects of mechanical flexibility and restrictions of the cardiac pump have been tentatively related to some constructional aspects of the icefish cardiomegaly, particularly, at the whole ventricular level, to the trabeculate type of myo-architecture, and, at the subcellular level, to the conflict in space economy between the exceptionally high mitochondrial densities and the consequent severe reduction in myofibrillar volume. On the basis of this morphodynamic approach, we suggest that the icefish may illustrate how a certain feature (I.e., an architectural cardiac design) common to the suborder and to most teleosts, and apparently with "irrelevant" properties, can become useful for a specialized purpose (i.e., volume pump design); and how, in contrast, the internal machinery construction, because of structural and ultrastructural constraints, may prevent these stenothermal sedentary teleosts from conquering niches requiring more active locomotory habits.

Electrocardiographic characterization of myocardial function in normoxic and hypoxic teleosts

Electrocardiography was applied to analyze cardiac function of four teleost species (Piaractus mesopotamicus, Hoplias malabaricus, Hoplias lacerdae and Cyprinus carpio) during normoxia and graded hypoxia. In these species, hypoxic bradycardia consistently occurred during severe hypoxia (below the critical oxygen tension - PcO2) and was accompanied by alterations in the ECG recordings. Three basic ECG alterations were demonstrable: 1) increase in the T wave area and amplitude, being more positive and with symmetrical morphology during severe hypoxia (P. mesopotamicus); 2) negative T wave in normoxia, changing to isodiphasic (Just above the PcO2) and positive (below the PcO2; H. malabaricus and H. lacerdae); 3) positive T wave in normoxia, changing to negative in severe hypoxia (5 mmHg; Cyprinus carpio). These findings indicate changes in the direction of ventricular repolarization during exposure to severe hypoxia, and the analysis of the ECGs in relation to the derivation line permitted the estimation of these drifts to be 17 degrees in P. mesopotamicus, 46 degrees in H. malabaricus, 43 degrees in H. lacerdae, and 32 degrees in C. carpio. The changes in the direction of ventricular repolarization were attributed to myocardial impairment due to insufficient oxygen supply, and support the idea of a relationship between cardiac dysfunction and the bradycardia developed during severe hypoxia.

Efectos del frío sobre la respiración mitocondrial del miocardio de ratas hipotiroideas tratadas con triiodotironina / Effects of cold on myocardial mitochondria respiration of rats with hypothyroidism treated with triiodothyronine

El presente trabajo estudió el efecto del frío sobre el consumo del oxígeno (CO) y la actividad *-glicerofosfato deshidrogenasa (*-GPD) en mitocondria cardíaca de ratas hipotiroideas (hipo) tratadas con T3, T4 o T4 más Acido lopanoico (IOP). Se usaron ratas Wistar macho de 200g de peso hechas hipotiroideas con la administración de I. Los animales fueron inyectadoss s.c., en dosis divididas, por 10 días, con una de las siguientes sustancias: T3, 300 ng/100g peso/día; T4, 2 *g/100g peso/día o T4 más IOP, 5 mg/100g peso/día, por 72 hs. previas al experimento. Una mitad de cada grupo fue mantenida a 4§C y el resto a 22§C, por 24 hs., y logo decapitados. Se aislaron las mitocondrias de corazón por métodos de rutina. El CO se midió polarográficamente usando L-malato, L-glutamato y malonato como sustratos. La actividad mitocondrial *-GPD se medió por un método microcolorimétrico. Los resultados correspondientes a 16 o 20 ratas/grupo (4 o 5 "pooles" de 4 corazones cada uno) fueron los isguientes: En las ratas mantenidas a 22§C el CO (en ng at. de oxíg./min/mg prot.; Estado 3) de las Hipo+T4 fue de 69 ñ 10; en el grupo tratado con T4+IOP fue de 75 ñ 11 y ...