Astragalus polysaccharides improve cardiomyopathy in STZ-induced diabetic mice and heterozygous (SOD2+/-) knockout mice

Oxidative stress plays an important role in the development of diabetic cardiomyopathy. In the present study, we determined whether the effect of astragalus polysaccharides (APS) on diabetic cardiomyopathy was associated with its impact on oxidative stress. Streptozotocin (STZ)-induced diabetic mice and heterozygous superoxide dismutase (SOD2+/-) knockout mice were administered APS. The hemodynamics, cardiac ultrastructure, and the apoptosis, necrosis and proliferation of cardiomyocytes were assessed to evaluate the effect of APS on diabetic and oxidative cardiomyopathy. Furthermore, H2O2 formation, oxidative stress/damage, and SOD activity in cardiomyocytes were evaluated to determine the effects of APS on cardiac oxidative stress. APS therapy improved hemodynamics and myocardial ultrastructure with reduced apoptosis/necrosis, and enhanced proliferation in cardiomyocytes from both STZ-induced diabetic mice and heterozygous SOD2+/- knockout mice. In addition, APS therapy reduced H2O2 formation and oxidative stress/damage, and enhanced SOD activity in both groups of mice. Our findings suggest that APS had benefits in diabetic cardiomyopathy, which may be partly associated with its impact on cardiac oxidative stress.

Effects of ovariectomy on the secretory apparatus in the right atrial cardiomyocytes of middle-aged mice

OBJECTIVE : The aim of the present study was to evaluate the effects of ovariectomy on the secretory apparatus of natriuretic peptides in right atrial cardiomyocytes. METHODS: Nine-month-old mice underwent bilateral ovariectomy or sham surgery. The blood exam of the ovariectomized mice showed results consistent with castrated females. Systolic blood pressure was measured after ovariectomy (9 mo of age) and at the moment of sacrifice (12 mo of age). Fragments of the right atrium were collected and prepared for electron microscopy examination. The following variables were quantified: the quantitative density and area of the natriuretic peptide granules, the relative volume of euchromatin in the nucleus, the number of pores per 10 μm of the nuclear membrane and the relative volumes of the mitochondria and Golgi complex. RESULTS: The cardiomyocytes obtained from ovariectomized mice indicated that the quantitative density and the area of secretory granules of natriuretic peptides were significantly lower compared with the sham-operated mice. Furthermore, there was a decrease in the relative volume of euchromatin, a lower density of nuclear pores, and lower relative volumes of the mitochondria and Golgi complex in the ovariectomized mice compared with the sham-operated mice. These findings suggest a pool with a low turnover rate, i.e., low synthesis and elimination of natriuretic peptides. CONCLUSION: A lack of estrogen caused hypotrophy of the secretory apparatus in right atrial cardiomyocytes that could explain the weak synthesis of natriuretic peptides in mice. Furthermore, one of the mechanisms of blood pressure control was lost, which may explain, in part, the elevated blood pressure in ovariectomized mice. .

The effects of electromagnetic fields on the ultrastructure of heart / Efectos de los campos electromagnéticos en la ultraestructura del corazón

Increasingly the use and convenience of electrical appliances in our daily lives are the cause of harmful effects caused by electromagnetic fields (EMF). The aim of this study was to research the effect of EMF on the ultrastructure of the heart in EMF exposed rats. In this study 45 male Sprague Dawley rats ranging in weight between 260 and 280 grams were used. The rats were divided into 3 groups, control (n:15), Sham (n:15) and EMF group (n: 15) and exposed for 14 days 3 hours per day; gauss levels at 2.5 were applied to the EMF group, while the sham group in the same environment in Plexiglas cage was kept for 14 days 3 hours per day without magnetic field exposure. Control group at 14/10 hours light dark cycle fed in normal cages for 14 days. After two weeks rats were sacrificed by 50mg/kg of Ketalar anesthesia and heart tissue fixed in 2.5 gluteraldehide. Routine follow up with electron microscopic assessment. Mitochondrial structures and cellular structures observed in all the groups were normal. Myofibrillar loss, dilatation of smooth endoplasmic reticulum, mitochondrial swelling or cristalysis was not observed. Intercalated disc degeneration and apoptosis of nucleus was not observed. Therefore, and as a result of our study we did not observe differences between control and EMF groups.

El uso y la comodidad de los aparatos eléctricos en nuestra vida cotidiana cada vez más son causa de efectos perjudiciales debido a los campos electromagnéticos(CEM).El objetivo de este estudio fue investigar el efecto de los CEM sobre la ultraestructura del corazón en ratas. Fueron utilizadas 45ratas Sprague Daw ley, con peso entre 260 y 280gramos. Las ratas fueron divididas en 3 grupos: control (n: 15); Sham (n:15), y grupo expuesto a CEM (n:15) durante 14 días,3 horas por día. Se aplicó niveles de 2,5gaussal grupo expuesto a CEM, mientras que el grupo de tratamiento simulado en el mismo entorno en jaulas plexiglás se mantuvo durante 14 días 3 horas día, sin exposición a campo electromagnético. Grupo control alimentado en jaulas normales durante 14 días con ciclo luz/oscuridad de 14/10. Al termino de dos semanas las ratas fueron sacrificadas por medio de anestesia Ketalar 50mg/kg y el tejido del corazón fijado engluteraldehido al 2,5. Se realizó seguimiento de rutina con correspondiente evaluación de microscopía electrónica. Las estructuras mitocondriales y celular es observadas en todos los grupos eran normales. No se observó pérdida miofibrilar, tampoco aumento del volumen mitocondrial ni dilatación del retículo endoplásmico lisoocristalysis. No se observó degeneración de los discosintercaladoso apoptosis de núcleo. Por lo tanto,y como resultado de nuestro estudio no encontramos diferencias entre los grupos control y CEM.

Fluoxetine effects on mitochondrial ultrastructure of right ventricle in rats exposed to cold stress / Efeitos da fluoxetina sobre a ultraestrutura mitocondrial no ventrículo direito de ratos expostos ao estresse pelo frio

OBJECTIVE: To assess fluoxetine effects on mitochondrial structure of the right ventricle in rats exposed to cold stress. METHODS: The experimental study procedures were performed in 250-300g male EPM-Wistar rats. Rats (n=40) were divided into four groups: 1) Control group (CON); 2) Fluoxetine (FLU); 3) Induced hypothermia (IH) and; 4) Induced hypothermia treated with fluoxetine (IHF). Animals of FLU group were treated by the administration of gavages containing 0.75 mg/kg/day fluoxetine during 40 days. The induced hypothermia was obtained by maintaining the groups 3 and 4 in a freezer at -8ºC for 4 hours. The animals were sacrificed and fragments of the right ventricle (RV) were removed and processed prior to performing electron microscopic analysis. RESULTS: The ultrastructural changes in cardiomyocytes were quantified through the number of mitochondrial cristae pattern (cristolysis). The CON (3.85 percent), FLU (4.47 percent) and IHF (8.4 percent) groups showed a normal cellular structure aspect with preserved cardiomyocytes cytoarchitecture and continuous sarcoplasmic membrane integrity. On the other hand, the IH (34.4 percent) group showed mitochondrial edema and lysis in cristae. CONCLUSION: The ultrastructural analysis revealed that fluoxetine strongly prevents mitochondrial cristolysis in rat heart, suggesting a protector effect under cold stress condition.

OBJETIVO: Analisar os efeitos da fluoxetina sobre a estrutura mitocondrial do ventrículo direito de ratos expostos ao estresse pelo frio. MÉTODOS: Os procedimentos do estudo foram realizados em ratos Wistar-EPM (250-300g) machos. Os ratos (n=40) foram divididos em quatro grupos: 1) Controle (CON); 2) Fluoxetina (FLU); 3) Induzidos à hipotermia (IH) e; 4) Induzidos à hipotermia tratados com fluoxetina (IHF). O grupo FLU foi tratado com gavagem contendo 0,75 mg/kg/dia de fluoxetina durante 40 dias. O estresse induzido pelo frio foi realizado mantendo os grupos 3 e 4 em um freezer (-8ºC) por quatro horas. Os animais foram sacrificados e fragmentos do ventrículo direito (VD) foram removidos e processados antes de serem conduzidos para a microscopia eletrônica. RESULTADOS: As alterações ultraestruturais dos cardiomiócitos foram quantificadas pelo número padrão de cristas mitocondriais (cristólises). Os grupos CON (3,85 por cento), FLU (4,47 por cento) e IHF (8,4 por cento) mostraram aspecto normal de suas estruturas celulares com a citoarquitetura dos cardiomiócitos preservada com integridade sarcoplasmática contínua. Por outro lado, o grupo IH (34,4 por cento) apresentou edema mitocondrial e lise nas cristas. CONCLUSÃO: A análise ultraestrutural revelou que a fluoxetina previne fortemente cristólises mitocondriais em miocárdio de ratos, sugerindo possível efeito protetor na condição de estresse induzido pelo frio.

Efeito do treinamento físico em alterações induzidas pelo envelhecimento no músculo papilar do rato / Effect of exercise training on aging-induced changes in rat papillary muscle / Efecto del entrenamiento físico en alteraciones inducidas por el envejecimiento en el músculo papilar de la rata

FUNDAMENTO: Os efeitos do envelhecimento no músculo papilar têm sido amplamente demonstrados, mas não há dados disponíveis sobre os efeitos do exercício nas alterações relacionadas à idade. OBJETIVO: Analisar os efeitos do envelhecimento nas propriedades morfológicas e quantitativas do músculo papilar e investigar se um programa contínuo de exercícios moderados pode exercer um efeito protetor contra as conseqüências do envelhecimento. MÉTODOS: Microscopia eletrônica foi utilizada para estudar a densidade dos miócitos, capilares e tecido conectivo e área transversal dos miócitos do músculo papilar no ventrículo esquerdo de ratos Wistar de 6 e 13 meses, não-treinados e submetidos a exercícios. RESULTADOS: Como esperado, a densidade de volume dos miócitos diminui significantemente (p<0,05) com a idade. A densidade de comprimento dos capilares também diminui com a idade, mas não de forma significante. A fração de volume intersticial do tecido do músculo capilar aumenta significantemente com a idade (P<0,05). O número de perfis de miócitos mostrou uma redução de 20% que foi acompanhada de hipertrofia dos miócitos no envelhecimento (P<0,05). Animais submetidos a uma sessão diária de 60 minutos, 5 dias/semana a 1,8 km.h-1 de corrida moderada em esteira ergométrica durante 28 semanas mostraram uma reversão de todos os efeitos do envelhecimento observados no músculo papilar. CONCLUSÃO: O presente estudo apóia o conceito de que treinamento físico de longo prazo impede as mudanças deletérias relacionadas à idade no músculo capilar.

BACKGROUND: The effects of aging on papillary muscle have been widely demonstrated, but no data on the effects of exercise on the age-related changes are available. OBJECTIVE: To analyze the effects of aging on the morphological and quantitative properties of papillary muscle and investigate whether a long-term moderate exercise program would exert a protective effect against the effects of aging. METHODS: We used electron microscopy to study the density of myocytes, capillaries and connective tissue and the cross-sectional area of myocytes of the papillary muscle of the left ventricle of 6- and 13-month-old untrained and exercised Wistar rats. RESULTS: As expected, the volume density of myocytes declined significantly (p<0.05) with aging. The length density of myocardial capillaries also declined with aging, but not significantly. The interstitial volume fraction of the papillary muscle tissue increased significantly (P<0.05) with age. The number of myocyte profiles showed a reduction of 20% that was accompanied by myocyte hypertrophy in the aged rats (P<0.05). Animals submitted to a 60-minute daily session,, 5 days/wk at 1.8 km.h-1 of moderate running on a treadmill for 28 weeks showed a reversion of all the observed aging effects on papillary muscle. CONCLUSION: The present study supports the concept that long-term exercise training restrains the aging-related deleterious changes in the papillary muscle.

FUNDAMENTO: Los efectos del envejecimiento en el músculo papilar han sido demostrados de modo amplio, pero no hay datos disponibles sobre los efectos del ejercicio en las alteraciones relacionadas a la edad. OBJETIVO: Analizar los efectos del envejecimiento en las propiedades morfológicas y cuantitativas del músculo papilar e investigar si un programa continuo de ejercicios moderados puede ejercer un efecto protector contra las consecuencias del envejecimiento. MÉTODOS: Se utilizó microscopia electrónica para estudiar la densidad de los miocitos, capilares y tejido conectivo, así como el área transversal de los miocitos del músculo papilar en el ventrículo izquierdo de ratas Wistar de 6 y 13 meses, no entrenadas y sometidas a ejercicios. RESULTADOS: Como se esperaba, la densidad de volumen de los miocitos disminuye significantemente (p<0,05) con el avance de la edad. La densidad de longitud de los capilares también disminuye con la edad, pero no de forma significante. La fracción de volumen intersticial del tejido del músculo capilar aumenta significantemente con el avance de la edad (P<0,05). El número de perfiles de miocitos mostró una reducción del 20%, seguida de su hipertrofia en el envejecimiento (P<0,05). Sometidos a una sesión diaria de 60 minutos, 5 días/semana a 1,8 km.h-1 de corrida moderada en estera ergométrica durante 28 semanas, los animales mostraron una reversión de todos los efectos del envejecimiento observados en el músculo papilar. CONCLUSIÓN: El presente estudio apoya el concepto de que entrenamiento físico de largo plazo impide los cambios letales en el músculo capilar relacionados a la edad.

Effects of statin and aerobic physical exercise association in the cardiomyocytes of the rat: morphometric study / Efectos de la asociación de estatina y del ejercicio aeróbico en los cardiomiocitos de rata: estudio morfométrico

Physical exercise and statins, recommended interventions to dyslipidaemia treatment, are independently related to cardiomyocytes alterations, characterized by miocardic hypertrophy and apoptosis, respectively. Thus, the objective of the present study was to analyze the effects of statin and aerobic physical exercise association in the morphometric parameters of cardiac cell nucleus. 40 male rats adults were divided into four groups: exercised (DE); sedentary (DS), exercised and statin use (DES); sedentary and statin use (DSS). The animals received during the whole experimental period a hiperlipidic diet added 20 percent of coconut oil and 1.25 percent of cholesterol; after 30 days of its ingestión, a blood collection was made to verify the dyslipidaemia. Simvastatin (20 mg) was taken five days a week, during eight weeks. During this period, the animals exercised 60 minutes daily in the treadmill. After the last day of the protocol, the cardiac muscle was collected and maintained in liquid nitrogen (-180°C); the cuts were stained by Hematoxilin-Eosin method, and the cardiac fibers were submitted to the nuclear morphometric analyses. The data were analyzed using descriptive analyses, paired T test, Kruskal-Wallis test and Dunn post hoc test; for all analyses, it was adopted p<0.05. It was verified that the group receiving statin presented values statistically significant in comparison to the other groups, in the tridimensional and linear variables. The exercised and statin group, the values obtained in the morphometric analyses were similar to the control group. It is suggested that statins alone can cause alterations in the nucleus of cardiac cells that can be related to apoptosis occurrence and, when exercise is practiced associated to statin administration, the effects of statin can be reduced, what can be related to beneficial adaptations of cardiac mitochondrial in response to physical exercise, turning them more resistant to apoptotic stimuli.

El ejercicio físico y las estatinas, intervenciones recomendadas para tratamiento de la dislipidemia, están independientemente relacionadas con las alteraciones de los cardiomiocitos, que se caracterizan por hipertrofia miocárdica y apoptosis, respectivamente. El objetivo del presente estudio fue analizar los efectos de la asociación de estatinas y el ejercicio físico aeróbico en los parámetros morfométricos del núcleo de células cardíacas. 40 ratas macho adultas se dividieron en cuatro grupos: ejercitadas (DE); sedentarias (DS), ejercitadas y con uso de estatina (DES), sedentarias y con uso de estatina (DSS). Los animales recibieron durante todo el período experimental una dieta hiperlipidemica añadiendo 20 por ciento de aceite de coco y 1,25 por ciento de colesterol. Después de 30 días de su ingestión, se les extrajo sangre para verificar la dislipidemia. Los ejemplares ingirieron Simvastatina (20 mg) cinco días a la semana, durante ocho semanas. Durante este período, los animales ejercitaron 60 minutos diarios en la rueda de andar. Después del último día del protocolo,los animales fueron sacrificados y se les extrajo músculo cardiaco que fue mantenido en nitrógeno líquido (-180°C). De este material se obtuvieron cortes que fueron teñidos por el método de hematoxilina-eosina y las fibras cardiacas fueron sometidas a análisis morfométrico nuclear. Los datos fueron analizados mediante el análisis descriptivo, prueba de la t de Student, prueba de Kruskal-Wallis y Dunn test post hoc. Para todos los análisis fue aprobado p <0,05. Se comprobó que el grupo que recibió estatinas presentó valores estadísticamente significativos en comparación con los otros grupos, en las variables lineales y tridimensionales. En el grupo ejercitado y estatina, los valores obtenidos de los análisis morfométricos fueron similares a los del grupo control. Se sugiere que las estatinas, por sí solas, pueden causar alteraciones en el núcleo de las células cardiacas ...

O miocárdio na tetralogia de Fallot: estudo histológico e morfométrico / The myocardium in tetralogy of Fallot: a histological and morphometric study / El miocardio en la tetralogía de Fallot: estudio histológico y morfométrico

FUNDAMENTO: Pacientes com tetralogia de Fallot freqüentemente cursam com disfunção ventricular no período pós-operatório. A base histológica dessa alteração funcional tem sido pouco estudada. OBJETIVO: Avaliar, em espécimes anatômicos, o remodelamento miocárdico comparando as regiões subepicárdica e subendocárdica, especialmente por esta última ser facilmente abordável por meio de biópsias endomiocárdicas. MÉTODOS:Análises em cortes transmurais de miocárdio da via de entrada, parede anterior e infundíbulo do ventrículo direito (VD) e da parede livre do esquerdo (VE), foram avaliados quanto ao grau de hipertrofia de cardiomiócitos, de vascularização e fibrose intersticial. RESULTADOS:O diâmetro médio dos cardiomiócitos do subendocárdio é semelhante ao do subepicárdio em todas as regiões, com exceção do infundíbulo do VD, em que os subendocárdicos se mostraram significativamente maiores em relação aos do subepicárdio (p=0,007). A quantidade de colágeno intersticial encontra-se nos limites superiores do normal e foi similar nas camadas subendocárdicas, comparada à subpericárdica de cada região, sendo, todavia, maior na via de entrada e na parede anterior do VD, do que na parede lateral do VE. A densidade numérica de capilares do subendocárdio foi semelhante à do subepicárdio e esteve menor que a média menos dois desvios-padrão do normal em todas as regiões e camadas, com exceção do infundíbulo, em que o subepicárdio mostrava valores normais e o subendocárdio valores menores que a média menos dois desvios-padrão. CONCLUSÃO: As alterações do miocárdio pós-natal na tetralogia de Fallot estão distribuídas homogeneamente nas metades subepicárdica e subendocárdica das paredes ventriculares, com exceção do infundíbulo, que apresenta características peculiares de remodelamento e que, portanto, não é representativo das demais regiões e camadas ventriculares para estudos morfométricos.

BACKGROUND: Patients with Tetralogy of Fallot frequently develop ventricular dysfunction in the postoperative period. The histological basis of this functional alteration has been scarcely studied. OBJECTIVE: To evaluate myocardial remodeling in anatomical specimens, comparing the subepicardial and subendocardial regions, especially because the subendocardial region is easily approached by means of endomyocardial biopsy. METHODS: Transmural sections of myocardium from the right ventricular (RV) inflow tract, anterior wall and infundibulum, and from the left ventricular (LV) free wall were evaluated regarding the degree of cardiomyocyte hypertrophy, vascularization and interstitial fibrosis were analyzed. RESULTS: The mean diameter of subendocardial cardiomyocytes is similar to that of subepicardial cardiomyocytes in all regions, except for the RV infundibulum, in which subendocardial cardiomyocytes are significantly larger in relation to those of the subepicardium (p=0.007). The amount of interstitial collagen is in the upper limits of normal and was similar in the subendocardial layers in comparison with the subpericardial layer of each region; however, it was greater in the inflow tract and RV anterior wall than in the LV lateral wall. The numerical density of subendocardial capillaries was similar to that of the subepicardium and was lower than the mean minus two standard deviations of normal in all regions and layers, except for the infundibulum, in which the subepicardium showed normal values and the subendocardium showed values lower than the mean minus two standard deviations. CONCLUSION: The postnatal myocardial changes in Tetralogy of Fallot are homogeneously distributed in the subepicardial and subendocardial halves of the ventricular walls, except for the infundibulum, which has peculiar remodeling characteristics and, therefore, is not representative of the other ventricular regions and layers for morphometric studies.

FUNDAMENTO: Frecuentemente, pacientes con tetralogía de Fallot cursan con disfunción ventricular en el período postoperatorio. La base histológica de esa alteración funcional ha sido poco estudiada. OBJETIVO: Evaluar, en especímenes anatómicos, la remodelación miocárdica comparándose las regiones subepicárdica y subendocárdica, sobre todo por esta última ser fácilmente abordable por medio de biopsias endomiocárdicas. MÉTODOS: Se evaluaron análisis en cortes transmurales de miocardio de la vía de entrada, pared anterior e infundíbulo del ventrículo derecho (VD) y de la pared libre del izquierdo (VI), en cuanto al grado de hipertrofia de cardiomiocitos, de vascularización y fibrosis intersticial. RESULTADOS: El diámetro promedio de los cardiomiocitos del subendocardio se asemeja al del subepicardio en todas las regiones, con excepción del infundíbulo del VD, en que los subendocárdicos se mostraron significativamente mayores con relación a los del subepicardio (p=0,007). La cantidad de colágeno intersticial se encuentra en los límites superiores al normal y fue similar en las camadas subendocárdicas, comparada a la subpericárdica de cada región; pero se mostró mayor en la vía de entrada y en la pared anterior del VD, que en la pared lateral del VI. La densidad numérica de capilares del subendocardio se asemejó a la del subepicardio y se mostró menor que el promedio menos dos desviaciones estándar del normal, en todas las regiones y capas, con excepción del infundíbulo, en lo que el subepicardio revelaba valores normales y el subendocardio valores menores que el promedio menos dos desviaciones estándar. CONCLUSIÓN: Las alteraciones del miocardio postnatal en la tetralogía de Fallot están distribuidas de modo homogéneo en las mitades subepicárdica y subendocárdica de las paredes ventriculares, a excepción del infundíbulo, que presenta características peculiares de remodelación y que, por lo tanto, no es representativo de las otras regiones...

In vitro and in vivo resuscitation with adenosine retains cardiomyocyte structure and function following hemorrhagic shock in rats

Successful treatment of hemorrhage requires restoration of normal cardiac function following resuscitation. However, many interventions used to attempt to restore cardiac function may cause additional myocardial injury, cardiac dysfunction and failure. The purpose of this study was to examine the ability of therapeutic intervention using adenosine to protect the heart from contractile dysfunction and post-resuscitation injury following hemorrhagic shock. Male Spargue-Dawley rats were divided into 3 groups: 1] In vivo hemorrhagic shock [1hour] followed by in vitro treatment with adenosine and ex vivo resuscitation using the Langendorff apparatus [60 minutes], 2] In vivo hemorrhagic shock [1 hour] followed by in vivo treatment with 20 microM adenosine and resuscitation [30 minutes] then ex vivo perfusion [60 minutes] and 3] In vivo hemorrhagic shock [2 hours] followed by in vivo treatment with 20 microM adenosine and resuscitation [30 minutes] then ex vivo perfusion [60 minutes]. Arterial blood samples were collected for measurements of TNF-alpha. Treatment with adenosine before resuscitation from hemorrhagic shock significantly improved left ventricular contractile function compared to the untreated resuscitated group. Treatment with adenosine also decreased the inflammatory response to shock by lowering the levels of TNF. In conclusion, treatment with adenosine before resuscitation of hemorrhagic shock protected the heart from post-resuscitation myocardial dysfunction and injury in rats

Resuscitation with adenosine retains cardiomyocyte structure following hemorrhagic shock in rats

Despite the improvement in resuscitation strategies, the incidence of post-resuscitation myocardial injury and failure remains high. Hemorrhagic shock activates an inflammatory response that can lead to myocardial cellular injury. Adenosine has been shown to protect the heart against ischemia reperfusion injury. However, the cardioprotective effects of adenosine following hemorrhagic shock may reduce myocardial injury by decreasing the inflammatory response to shock in rats. After 60 min on hemorrhage, 10 rats were randomized in vivo resuscitation with [n=8] microM adenosine for 30 min. heart Biopsies were collected from histological and electron microscopy examination. Light microscopy demonstrated decreased neutrophil infiltration, absence of contraction band necrosis and hydropic degeneration in the adenosine treated group compared to the hemorrhage untreated. Electron microscopy showed relative preservation of myocardial structure with absence of mitochondrial swelling in the hemorrhage treated group. These findings suggest that treatment with adenosine before in vivo resuscitation of hemorrhagic shock protected the heart from post-resuscitation myocardial injury in rats and the mechanism could be mediated by lowering the inflammatory response to shock

Cold stress effects on cardiomyocytes nuclear size in rats: light microscopic evaluation / Efeitos do estresse pelo frio sobre o tamanho nuclear do cardiomiócito em ratos: avaliação por microscopia de luz

INTRODUÇÃO: Hipotermia corporal induzida e resfriamento do miocárdio são métodos efetivos em relação à proteção domiocárdio durante cirurgias cardíacas e isquemia. É descrito na literatura que a exposição a temperaturas extremamente baixas causa comprometimentos de miofilamentos e de cristas mitocondriais em cardiomiócitos, entretanto, nenhum estudo analisou os efeitos do estresse pelo frio no tamanho do núcleo dos cardiomiócios. OBJETIVOS: Analisar os efeitos do estresse agudo pelo frio sobre o tamanho do núcleo dos cardiomiócitos. MÉTODOS: O estudo foi realizado em ratos Wistar adultos, pesando 300-310g (n=20). Os ratos foram divididos em dois grupos: 1) Controle (CON) e; 2) Hipotermia induzido (IH). Os animais do grupo IH foram expostos a uma temperatura controlada de -8ºC, durante 4 horas uma única vez. Foi realizada análise histológica de fígados e glândulas adrenais para examinar a condição de estresse. O tamanho do núcleo dos cardiomiócitos foi examinado por três investigadores independentes com o mesmo critério padronizado e posteriormente analisado pelo coeficiente de correlação de Bartko (R>0,75=concordância positiva). Teste t de Student foi aplicado. O nível de significância foi considerado como P<0,05. RESULTADOS: O grupo exposto ao estresse pelo frio apresentou maior depleção de lipídio nas glândulas adrenais (P<0,05) e de glicogênio no fígado (P<0,05). O grupo induzido à hipotermia mostrou menor volume do núcleo de seus cardiomiócitos (108 + 1,7 µm³; P<0,05), reduziu em 76 por cento comparado ao grupo controle (142 + 2,3 µm³). Correlação de Bartko: CON=0,44; IH=0,96, a variação entre a média dos grupos foi significativamente diferente. CONCLUSÃO: Esses resultados sugerem que a exposição ao estresse agudo pelo frio induz redução do núcleo dos cardiomiócitos em ratos.

INTRODUCTION: Total body induced hypothermia and myocardial cooling are effective methods regarding myocardial protection during heart surgery and ischemia. It is described in previous studies that extreme low temperature exposure causes mitochondrial cristae and myofilament disarrangement in cardiomyocytes, however, no investigation has analyzed the effects of cold stress on nuclear size of cardiomyocytes. OBJECTIVES: To evaluate the effects of acute cold stress exposure on the nuclear size of cardiomyocytes in rats. METHODS: The experimental study procedures were performed on 300-310g adult male Wistar rats. Rats (n=20) were divided into two groups: 1) Control (CON) and; 2) Induced hypothermic (IH) group. Animals of IH group were exposed during 4 hours once at a controlled temperature of - 8ºC. It was performed histological analysis of liver and adrenal gland to examine the stress condition of animals. Cardiomyocytes nucleus size were examined by three independent investigators with the same and standardized criteria and analyzed by Bartko's intra-class correlation coefficient (R>0.75 = positive concordance). Student's t test was applied. The significance level was set at P<0.05. RESULTS: The induced hypothermic group presented higher lipid depletion in adrenal gland cells (P<0.05) and higher glycogen depletion in liver glycogen (P<0.05). The experimental group showed lower cardiomyocytes nuclear volume (108 + 1.7 µm³; P<0.05), it decreased in 76 percent compared to the control group (142 + 2.3 µm³). Bartko's correlation: CON=0.44; IH=0.96, variation analysis between group's means differences was significant. CONCLUSION: These data suggest that acute cold stress exposure induces cardiomyocytes nucleus size reduction in rats.

Protective role of antioxidant vitamin E and catechin on idarubicin-induced cardiotoxicity in rats

Idarubicin is an anthracycline antibiotic extensively used in acute leukemia. In the present study we investigated whether vitamin E and catechin can reduce the toxic effects of idarubicin. Vitamin E (200 IU kg-1 week-1), catechin (200 mg kg-1 week-1), idarubicin (5 mg kg-1 week-1), idarubicin + vitamin E (200 IU kg-1 week-1), and idarubicin + catechin (200 mg kg-1 week-1) combinations were given to male Sprague-Dawley rats weighing 210 to 230 g (N = 6/group). Idarubicin-treated animals exhibited a decrease in body and heart weight, a decrease in myocardial contractility, and changes in ECG parameters (P<0.01). Catechin + idarubicin- and vitamin E + idarubicin-treated groups exhibited similar alterations, but changes were attenuated in comparison to those in cardiac muscle of idarubicin-treated rats (P<0.05). Superoxide dismutase and catalase activity was reduced in the idarubicin-treated group (P<0.05). Glutathione peroxidase levels were decreased in the idarubicin-treated group (P<0.05) and reached maximum concentrations in the catechin- and catechin + idarubicin-treated groups compared to control (P<0.01). Malondialdehyde activity was decreased in the catechin + idarubicin-treated groups compared to control and increased in the other groups, reaching maximum concentrations in the vitamin E-treated group (P<0.01). In electron microscopy studies, swelling of the mitochondria and dilatation of the sarcoplasmic reticulum of myocytes were observed in the idarubicin-treated groups. In groups that were given idarubicin + vitamin E and idarubicin + catechin, the only morphological change was a weak dilatation of the sarcoplasmic reticulum. We conclude that catechin and vitamin E significantly reduce idarubicin-induced cardiotoxicity in rats