Atenuação da remodelação ventricular após infarto agudo do miocárdio / Attenuation of ventricular remodeling after myocardial acute infarction

Após o infarto agudo do miocárdio podem ocorrer complexas alterações da arquitetura ventricular, envolvendo tanto a região infartada como a região não infartada. Há alguns anos, essas alterações passaram a ser designadas como remodelação ventricular pós-infarto. Do ponto de vista clínico, a remodelação está associada ao pior prognóstico após a oclusão coronária. Assim, a remodelação predispõe o coração infartado à ruptura ventricular e é o substrato fisiopatológico para a posterior formação do aneurisma ventricular. Cronicamente, a remodelação está associada com maior prevalência de arritmias malignas, principalmente a taquicardia ventricular sustentada e a fibrilação ventricular. O aspecto mais relevante da remodelação pós-infarto, no entanto, é que esse processo desempenha papel fundamental na fisiopatologia da disfunção ventricular. Aspecto a ser considerado refere-se ao fato de que a evolução do processo de remodelação pode ser modificado por meio de diversas intervenções terapêuticas. Entre as estratégias para atenuar a remodelação ventricular destacam-se: terapia de reperfusão, inibidores da enzima conversora da angiotensina e antagonistas da angiotensina II, betabloqueadores, antagonistas da aldosterona e dispositivos de assistência circulatória.

After acute myocardial infarction (AMI), complex changes in ventricular architecture may occur involving the infarcted and the non-infarcted region. This set of adaptations, which includes changes in the composition, mass, volume and geometry of the heart, is known as myocardial remodeling. In relation to clinical significance, the intensity of the ventricular remodeling process is directly associated with worse prognosis, due to the higher incidence of aneurysm formation, ventricular rupture and arrhythmia, and is also associated with the progression of ventricular dysfunction. A relevant aspect to be considered is that a number of strategies have been employed to prevent or mitigate the process of ventricular remodeling following AMI, for instance: reperfusion therapy, angiotensin converting enzyme inhibitors and angiotensin II antagonists, beta-adrenergic receptor blockade, aldosterone antagonists, and left ventricular assist devices.

Retinoic acid prevents ventricular remodelling induced by tobacco smoke exposure in rats.

OBJECTIVE: Our objective was to test the hypothesis that retinoic acid supplementation could attenuate ventricular remodelling induced by tobacco smoke exposure in rats. METHODS AND RESULTS: Wistar rats were allocated into three groups: control (C, n = 8); exposed to tobacco smoke (ETS, n = 9); exposed to tobacco smoke and all-trans-retinoic acid (ETS-RA, n = 9). After two months, cardiac function and geometry were assessed by echocardiography, and geometry changes were confirmed by morphometric analysis. Data are expressed as mean +/- SD or medians (including the lower quartile and upper quartile). ETS showed higher normalized left ventricular diastolic diameters than groups C and ETS-RA (C = 18.4 +/- 3.57 mm/kg, ETS = 23.0 +/- 1.8, ETS-RA = 19.5 +/- 0.99; P <0.05) and systolic diameters (C = 8.25 +/- 2.16 mm/kg, ETS = 11.5 +/- 1.31, ETS-RA = 8.25 +/- 0.71 mm/kg; P < 0.05). ETS showed reduced ejection fraction (C= 91 +/- 2.0, ETS = 87 +/- 3.0, ETS-RA = 92 +/- 3.0; P < 0.05) and fractional shortening (C = 55.8 +/- 4.41%, ETS = 49.7 +/- 4.43%, ETS-RA = 57.6 +/- 5.15 %; P= 0.01) compared to C and ETS-RA. ETS had increased myocyte cross-sectional area (C = 294 +/- 21 mm2, ETS = 352 +/-44, ETS-RA = 310 +/- 35; P < 0.05) compared to C and ETS-RA. Considering all variables, there were no differences between groups C and ETS-RA. CONCLUSION: Retinoic acid prevented ventricular remodelling induced by tobacco smoke exposure.

Influence of lisinopril on cardiac remodeling induced by tobacco smoke exposure.

BACKGROUND: To investigate the effect of lisinopril on cardiac remodeling induced by smoking. MATERIAL/METHODS: Rats were allocated into 3 groups: group CON (n=8): control; group CSE (n=8): cigarette smoke exposure; group CSE-LIS (n=8): exposed to tobacco smoke and treated with lisinopril. RESULTS: After 2 months, the tail systolic pressure was lower in CSE-LIS (CON=116 +/-27 mm Hg, CSE=126+/-16, CSE-LIS=89+/-12; P<.001). CSE animals showed higher left ventricular systolic diameter (CON=8.25+/-2.16 mm/kg, CSE=11.5+/-1.3, CSE-LIS=9.27+/-2.00; P=.009) and myocyte cross-sectional area (CON=245+/-8 microm2, CSE=260+/-17, CSE-LIS=238+/-12; P=.01) than CON and CSE-LIS. The ejection fraction (CON =0.91+/-0.02, CSE=0.86+/-0.02, CSE-LIS=0.92+/-0.03; P=.002) and fractional shortening (CON=55.7+/-4.41%, CSE=48.7+/-3.43, CSE-LI=58.2+/-7.63; P=.006) were lower in CSE group than CON and CSE-LIS. CSE and CSE-LIS animals showed higher collagen amounts (CON=3.49+/-0.95%, CSE= 5.01+/-1.58, CSE-LIS=5.27+/-0.62; P=.009) than CON. CON group showed a higher connexin 43 amount in the intercalated disc (CON=3.70+/-0.38, CSE=2.13+/-0.53; CSE-LIS=2.17+/-0.73; P=.004) than CSE and CSE-LIS. There were no differences in IFN-gamma or TNF-alpha cardiac levels among the groups. CONCLUSIONS: Lisinopril attenuated both morphologic and functional abnormalities induced by exposure to tobacco smoke. In addition, this effect was associated with diminished blood pressure, but not alterations in connexin 43 distribution, cytokine production or collagen amount.

[Remodeling pattern and ventricular function in rats exposed to cigarette smoke].

BACKGROUND: The relevance of the remodeling pattern in the model of rats exposed to cigarette smoke is not known. OBJECTIVE: Analyzing the presence of different remodeling patterns in this model and its relation with the ventricular function. METHODS: Smoking rats (n=47) have been divided according to the geometry pattern, analyzed by echocardiogram: normal (normal mass index and normal relative wall thickness), concentric remodeling (normal mass index and increased relative wall thickness), concentric hypertrophy (increased mass index and increased relative wall thickness) and eccentric hypertrophy (increased mass index and normal relative wall thickness). RESULTS: Smoking rats presented one of the following geometry patterns: normal pattern, 51%; eccentric hypertrophy; 32%; concentric hypertrophy, 13% and concentric remodeling, 4%. The normal and eccentric hypertrophy groups presented smaller ejection fraction values and fractional shortening than the concentric hypertrophy group. Thirteen animals (28%) presented systolic dysfunction detected by the ejection fraction and by fractional shortening. In the single regression analysis, geometry patterns and mass index could not predict ventricular dysfunction (p<). On the other hand, the increased relative thickness of the wall could predict ventricular dysfunction in the single regression analysis (p<0.001) and in the multiple regression analysis after adjustment to the mass index (p=0.003). CONCLUSION: Rats exposed to cigarette smoke presented one of the four different remodeling patterns. Among the geometric variables analyzed, only the increased relative thickness of the left ventricle wall could predict ventricular dysfunction in this model.

Padrão de remodelação e função ventricular em ratos expostos à fumaça do cigarro / Estándar de remodelación y función ventricular en ratones expuestos al humo del cigarrillo / Remodeling pattern and ventricular function in rats exposed to cigarette smoke

FUNDAMENTO: A relevância do padrão de remodelação no modelo de ratos expostos à fumaça do cigarro não é conhecida. OBJETIVO: Analisar a presença de diferentes padrões de remodelação nesse modelo e sua relação com a função ventricular. MÉTODOS: Ratos fumantes (n=47) foram divididos de acordo com o padrão de geometria, analisado pelo ecocardiograma: normal (índice de massa normal e espessura relativa normal), remodelação concêntrica (índice de massa normal e espessura relativa aumentada), hipertrofia concêntrica (índice de massa aumentado e espessura relativa aumentada) e hipertrofia excêntrica (índice de massa aumentado e espessura relativa normal). RESULTADOS: Os ratos fumantes apresentaram um dos quatro padrões de geometria: padrão normal, 51 por cento; hipertrofia excêntrica:,32 por cento; hipertrofia concêntrica, 13 por cento e remodelação concêntrica, 4 por cento. Os grupos normal e hipertrofia excêntrica apresentaram menores valores de fração de ejeção e porcentagem de encurtamento que o grupo hipertrofia concêntrica. Treze animais (28 por cento) apresentaram disfunção sistólica, detectada pela fração de ejeção e pela porcentagem de encurtamento. Na análise de regressão univariada, os padrões de geometria e o índice de massa não foram fator de predição de disfunção ventricular (p>0,05). Por outro lado, o aumento da espessura relativa da parede foi fator de predição de disfunção ventricular na análise univariada (p<0,001) e na análise multivariada, após ajuste para o índice de massa (p=0,003). CONCLUSÃO: Ratos expostos à fumaça do cigarro apresentam um dos quatro diferentes padrões de remodelação. Entre as variáveis geométricas analisadas, somente o aumento da espessura relativa da parede do ventrículo esquerdo foi fator de predição de disfunção ventricular nesse modelo.

BACKGROUND: The relevance of the remodeling pattern in the model of rats exposed to cigarette smoke is not known. OBJECTIVE: Analyzing the presence of different remodeling patterns in this model and its relation with the ventricular function. METHODS: Smoking rats (n=47) have been divided according to the geometry pattern, analyzed by echocardiogram: normal (normal mass index and normal relative wall thickness), concentric remodeling (normal mass index and increased relative wall thickness), concentric hypertrophy (increased mass index and increased relative wall thickness) and eccentric hypertrophy (increased mass index and normal relative wall thickness). RESULTS: Smoking rats presented one of the following geometry patterns: normal pattern, 51 percent; eccentric hypertrophy; 32 percent; concentric hypertrophy, 13 percent and concentric remodeling, 4 percent. The normal and eccentric hypertrophy groups presented smaller ejection fraction values and fractional shortening than the concentric hypertrophy group. Thirteen animals (28 percent) presented systolic dysfunction detected by the ejection fraction and by fractional shortening. In the single regression analysis, geometry patterns and mass index could not predict ventricular dysfunction (p<). On the other hand, the increased relative thickness of the wall could predict ventricular dysfunction in the single regression analysis (p<0,001) and in the multiple regression analysis after adjustment to the mass index (p=0,003). CONCLUSION: Rats exposed to cigarette smoke presented one of the four different remodeling patterns. Among the geometric variables analyzed, only the increased relative thickness of the left ventricle wall could predict ventricular dysfunction in this model.

FUNDAMENTO: No se conoce la relevancia del estándar de remodelación en el modelo de ratones expuestos al humo del cigarrillo. OBJETIVO: Analizar la presencia de diferentes estándares de remodelación en este modelo y su relación con la función ventricular. MÉTODOS: Ratones fumadores (n=47) se dividieron según el estándar de geometría, analizado por el ecocardiograma: normal (índice de masa normal y espesor relativo normal), remodelación concéntrico (índice de masa normal y espesor relativo aumentado), hipertrofia concéntrica (índice de masa aumentado y espesor relativo aumentado) y hipertrofia excéntrica (índice de masa aumentado y espesor relativo normal). RESULTADOS: Los ratos fumadores presentaron uno de los cuatro estándares de geometría: estándar normal, el 51 por ciento; hipertrofia excéntrica: el 32 por ciento; hipertrofia concéntrica, el 13 por ciento y remodelación concéntrica, el 4 por ciento. Los grupos normal e hipertrofia excéntrica presentaron menores valores de fracción de eyección y porcentaje de acortamiento que el grupo hipertrofia concéntrica. Trece animales (28 por ciento) presentaron disfunción sistólica, detectada por la fracción de eyección y por el porcentaje de acortamiento. En el análisis de regresión univariado, los estándares de geometría y el índice de masa no fueron factor de predicción de disfunción ventricular (p > 0,05). Por otro lado, el aumento del espesor relativo de la pared fue factor de predicción de disfunción ventricular en el análisis univariado (p < 0,001) y en el análisis multivariado, tras ajuste para el índice de masa (p = 0,003). CONCLUSIÓN: Ratones expuestos al humo del cigarrillo presentan uno de los cuatro diferentes estándares de remodelación. Entre las variables geométricas analizadas, solamente el aumento del espesor relativo de la pared del ventrículo izquierdo del factor de predicción de disfunción ventricular en este modelo.

Role of lipoperoxidation in the remodeling intensification induced by beta-carotene after infarction.

BACKGROUND: The mechanisms involved in the biggest remodeling caused by the post-infarct beta-carotene are unknown. OBJECTIVE: To analyze the role of lipoperoxidation in the ventricular remodeling after infarct of the myocardium in rats supplemented with beta-carotene. METHODS: Rats were infarcted and divided into two groups: C (control) and BC (500mg/kg/regimen). After six months, echocardiogram and biochemical evaluation were performed. The t test was used, with 5% significance. RESULTS: The animals from BC group presented highest means of the diastolic (C = 1.57 +/- 0.4 mm(2)/g, BC = 2.09 +/- 0.3 mm(2)/g; p < 0.001) and systolic (C = 1.05 +/- 0.3 mm(2)/g, BC = 1.61 +/- 0.3 mm(2)/g; p < 0.001) areas of LV, which were adapted according to the rat's body weight. The systolic function of LV, evaluated by the area variation fraction, was lower in the animals supplemented with beta-carotene (C = 31.9 +/- 9.3%, BC = 23.6 +/- 5.1%; p = 0.006). The animals supplemented with beta-carotene presented higher values of the E/A relation (C = 2.7 +/- 2.5, BC = 5.1 +/- 2.8; p = 0.036). No differences were found between the groups concerning the cardiac levels of the GSH (C = 21 +/- 8 nmol/mg of protein, BC = 37 +/- 15 nmol/mg of protein; p = 0.086), GSSG (C = 0.4 (0.3-0.5) nmol/g of protein, BC = 0.8 (0.4-1.0; p = 0.19) of protein; p = 0.246) and lipoperoxides (C = 0.4 +/- 0.2 nmol/mg of tissue, BC = 0.2 +/- 0.1 nmol/mg of tissue; p = 0.086). CONCLUSION: The highest remodeling in infarcted rats supplemented with beta-carotene does not depend on the lipoperoxidation.

Effects of the administration of beta-blockers on ventricular remodeling induced by cigarette smoking in rats.

BACKGROUND: The role of the adrenergic system on ventricular remodeling induced by cigarette smoking is unknown. OBJECTIVES: To investigate the influence of propranolol on ventricular remodeling induced by exposure to tobacco smoke. METHODS: Rats were divided into three groups: 1) C, n=10--control group; 2) F, n=10--animals exposed to tobacco smoke; 3) BB, n=10--animals receiving propranolol and exposed to tobacco smoke (40 mg/kg/day). After 2 months, the animals underwent echocardiographic and morphometric analyses. One-way ANOVA (mean +/- standard deviation) or the Kruskal-Wallis test (median and interquartile interval) was used. RESULTS: Group BB showed a lower heart rate than group F (C = 358 +/- 74 bpm, F = 374 +/- 53 bpm, BB = 297 +/- 30; P = 0.02). Group F showed greater end-diastolic diameters (C = 18.6 +/- 3.4 mm/kg, F = 22.8 +/- 1.8 mm/kg, BB = 21.7 +/- 1.8 mm/kg; P = 0.003) and left ventricular (LV) end-systolic diameters (C = 8.6 +/- 2.1 mm/kg, F = 11.3 +/- 1.3 mm/kg, BB = 9.9 +/- 1.2 mm/kg; P = 0.004), adjusted for body weight (BW) and a tendency towards a lower ejection fraction (C = 0.90 +/- 0.03, F = 0.87 +/- 0.03, BB =0.90 +/- 0.02; P = 0.07) than group C. Group BB showed a tendency towards a lower LV/BW ratio than group F (C = 1.94 (1.87 - 1.97), F = 2.03 (1.9-2.1) mg/g, BB = 1.89 (1.86-1.94); P = 0.09). CONCLUSION: Administration of propranolol attenuated some of the variables of ventricular remodeling induced by the exposure to tobacco smoke in rats.

The role of oxidative stress and lipid peroxidation in ventricular remodeling induced by tobacco smoke exposure after myocardial infarction.

OBJECTIVE: To evaluate the roles of oxidative stress and lipid peroxidation in the ventricular remodeling that is induced by tobacco smoke exposure after myocardial infarction. METHODS: After induced myocardial infarction, rats were allocated into two groups: C (control, n=25) and ETS (exposed to tobacco smoke, n=24). After 6 months, survivors were submitted to echocardiogram and biochemical analyses. RESULTS: Rats in the ETS group showed higher diastolic (C = 1.52 +/- 0.4 mm(2), ETS = 1.95 +/- 0.4 mm(2); p=0.032) and systolic (C = 1.03 +/- 0.3, ETS = 1.36 +/- 0.4 mm(2)/g; p=0.049) ventricular areas, adjusted for body weight. The fractional area change was smaller in the ETS group (C = 30.3 +/- 10.1 %, ETS = 19.2 +/- 11.1 %; p=0.024) and E/A ratios were higher in ETS animals (C = 2.3 +/- 2.2, ETS = 5.1 +/- 2.5; p=0.037). ETS was also associated with a higher water percentage in the lung (C = 4.8 (4.3-4.8), ETS = 5.5 (5.3-5.6); p=0.013) as well as higher cardiac levels of reduced glutathione (C = 20.7 +/- 7.6 nmol/mg of protein, ETS = 40.7 +/- 12.7 nmol/mg of protein; p=0.037) and oxidized glutathione (C = 0.3 +/- 0.1 nmol/g of protein, ETS = 0.9 +/- 0.3 nmol/g of protein; p=0.008). No differences were observed in lipid hydroperoxide levels (C = 0.4 +/- 0.2 nmol/mg of tissue, ETS = 0.1 +/- 0.1 nmol/mg of tissue; p=0.08). CONCLUSION: In animals exposed to tobacco smoke, oxidative stress is associated with the intensification of ventricular remodeling after myocardial infarction.

Papel da lipoperoxidação na intensificação da remodelação causada pelo betacaroteno após o infarto / Rol de la lipoperoxidación en la intensificación de la remodelación ocasionada por el betacaroteno tras infarto / Role of lipoperoxidation in the remodeling intensification induced by beta-carotene after infarction

FUNDAMENTO: Os mecanismos envolvidos na maior remodelação causada pelo betacaroteno após o infarto são desconhecidos. OBJETIVO: Analisar o papel da lipoperoxidação na remodelação ventricular após o infarto do miocárdio, em ratos suplementados com betacaroteno. MÉTODOS: Ratos foram infartados e distribuídos em dois grupos: C (controle) e BC (500mg/kg/dieta). Após seis meses, foram realizados ecocardiograma e avaliação bioquímica. Utilizamos o teste t, com significância de 5 por cento. RESULTADOS: Os animais do grupo BC apresentaram maiores médias das áreas diastólicas (C = 1,57 ± 0,4 mm²/g, BC = 2,09 ± 0,3 mm²/g; p < 0,001) e sistólicas (C = 1,05 ± 0,3 mm²/g, BC = 1,61 ± 0,3 mm²/g; p < 0,001) do VE, ajustadas ao peso corporal do rato. A função sistólica do VE, avaliada pela fração de variação de área, foi menor nos animais suplementados com betacaroteno (C = 31,9 ± 9,3 por cento, BC = 23,6 ± 5,1 por cento; p = 0,006). Os animais suplementados com betacaroteno apresentaram valores maiores da relação E/A (C = 2,7 ± 2,5, BC = 5,1 ± 2,8; p = 0,036). Não foram encontradas diferenças entre os grupos em relação aos níveis cardíacos de GSH (C = 21 ± 8 nmol/mg de proteína, BC = 37 ±15 nmol/mg de proteína; p = 0,086), GSSG (C = 0,4 (0,3-0,5) nmol/g de proteína, BC = 0,8 (0,4-1,0; p = 0,19) de proteína; p = 0,246) e lipoperóxidos (C = 0,4 ± 0,2 nmol/mg de tecido, BC = 0,2 ± 0,1 nmol/mg de tecido; p = 0,086). CONCLUSÃO: A maior remodelação em animais infartados e suplementados com betacaroteno não depende da lipoperoxidação.

BACKGROUND: The mechanisms involved in the biggest remodeling caused by the post-infarct beta-carotene are unknown. OBJECTIVE: To analyze the role of lipoperoxidation in the ventricular remodeling after infarct of the myocardium in rats supplemented with beta-carotene. METHODS: Rats were infarcted and divided into two groups: C (control) and BC (500mg/kg/regimen). After six months, echocardiogram and biochemical evaluation were performed. The t test was used, with 5 percent significance. RESULTS: The animals from BC group presented highest means of the diastolic (C = 1.57 ± 0.4 mm²/g, BC = 2.09 ± 0.3 mm²/g; p < 0.001) and systolic (C = 1.05 ± 0.3 mm²/g, BC = 1.61 ± 0.3 mm²/g; p < 0.001) areas of LV, which were adapted according to the rat's body weight. The systolic function of LV, evaluated by the area variation fraction, was lower in the animals supplemented with beta-carotene (C = 31.9 ± 9.3 percent, BC = 23.6 ± 5.1 percent; p = 0.006). The animals supplemented with beta-carotene presented higher values of the E/A relation (C = 2.7 ± 2.5, BC = 5.1 ± 2.8; p = 0.036). No differences were found between the groups concerning the cardiac levels of the GSH (C = 21 ± 8 nmol/mg of protein, BC = 37 ± 15 nmol/mg of protein; p = 0.086), GSSG (C = 0.4 (0.3-0.5) nmol/g of protein, BC = 0.8 (0.4-1.0; p = 0.19) of protein; p = 0.246) and lipoperoxides (C = 0.4 ± 0.2 nmol/mg of tissue, BC = 0.2 ± 0.1 nmol/mg of tissue; p = 0.086). CONCLUSION: The highest remodeling in infarcted rats supplemented with beta-carotene does not depend on the lipoperoxidation.

FUNDAMENTO: Los mecanismos implicados en la mayor remodelación ocasionada por betacaroteno tras el infarto son desconocidos. OBJETIVO: Analizar el rol que juega la lipoperoxidación en la remodelación ventricular tras el infarto de miocardio, en ratas suplementadas con betacaroteno. MÉTODOS: Se había inducido a un infarto a las ratas y se las distribuyó en grupos: C (control) y BC (500mg/kg/dieta). Tras seis meses, se realizaron ecocardiograma y evaluación bioquímica. Utilizamos la prueba t, con significancia del 5 por ciento. RESULTADOS: Los animales del grupo BC presentaron mayores promedios de las áreas diastólicas (C = 1,57 ± 0,4 mm²/g, BC = 2,09 ± 0,3 mm²/g; p < 0,001) y sistólicas (C = 1,05 ± 0,3 mm²/g, BC = 1,61 ± 0,3 mm²/g; p < 0,001) del VI, ajustadas al peso corporal de la rata. La función sistólica del VI, evaluada por la fracción de variación de área, fue menor en los animales suplementados con betacaroteno (C = 31,9 ± 9,3 por ciento, BC = 23,6 ± 5,1 por ciento; p = 0,006). Los animales suplementados con betacaroteno presentaron valores mayores de la relación E/A (C = 2,7 ± 2,5, BC = 5,1 ± 2,8; p = 0,036). No se encontraron diferencias entre los grupos con relación a los niveles cardiacos de GSH (C = 21 ± 8 nmol/mg de proteína, BC = 37 ±15 nmol/mg de proteína; p = 0,086), GSSG (C = 0,4 (0,3-0,5) nmol/g de proteína, BC = 0,8 (0,4-1,0; p = 0,19) de proteína; p = 0,246) y lipoperóxidos (C = 0,4 ± 0,2 nmol/mg de tejido, BC = 0,2 ± 0,1 nmol/mg de tejido; p = 0,086). CONCLUSIÓN: La mayor remodelación en animales infartados y suplementados con betacaroteno no depende de la lipoperoxidación.

Efeitos da administração de beta-bloqueador na remodelação ventricular induzida pelo tabagismo em ratos / Efectos de la administración de betabloqueante en la remodelación ventricular inducida por el tabaquismo en ratas / Effects of the administration of beta-blockers on ventricular remodeling induced by cigarette smoking in rats

FUNDAMENTO: O papel do sistema adrenérgico na remodelação induzida pelo tabagismo é desconhecido. OBJETIVO: Investigar a influência do propranolol na remodelação induzida pela exposição à fumaça de cigarro. MÉTODOS: Ratos foram alocados em três grupos: 1) C, n=10 - animais controle; 2) F, n=10 - animais expostos à fumaça de cigarro; 3) BB, n=10 - animais expostos à fumaça de cigarro e que receberam propranolol (40 mg/kg/dia). Após dois meses, os animais foram submetidos a estudo ecocardiográfico e morfométrico. Utilizou-se análise de variância (ANOVA) de uma via (média ± desvio padrão) ou Kruskal-Wallis (mediana e intervalo interquartil). RESULTADOS: O Grupo BB apresentou menor frequência cardíaca que o Grupo F (C = 358 ± 74 btm, F = 374 ± 53 bpm, BB = 297 ± 30; P = 0,02). O Grupo F apresentou maiores diâmetros diastólicos (C = 18,6 ± 3,4 mm/kg, F = 22,8 ± 1,8 mm/kg, BB = 21,7 ± 1,8 mm/kg; P = 0,003) e sistólicos (C = 8,6 ± 2,1 mmkg, F = 11,3 ± 1,3 mm/kg, BB = 9,9 ± 1,2 mm/kg; P = 0,004) do ventrículo esquerdo (VE), ajustado ao peso corporal (PC) e tendência de menor fração de ejeção (C = 0,90 ± 0,03, F = 0,87 ± 0,03, BB =0,90 ± 0,02; P = 0,07) que o Grupo C. O Grupo BB apresentou tendência de menor relação VE/PC que o Grupo F (C = 1,94 (1,87 - 1,97), F = 2,03 (1,9-2,1) mg/g, BB = 1,89 (1,86-1,94); P = 0,09). CONCLUSÃO: A administração de propranolol atenuou algumas variáveis da remodelação ventricular induzida pela exposição à fumaça do cigarro em ratos.

BACKGROUND: The role of the adrenergic system on ventricular remodeling induced by cigarette smoking is unknown. OBJECTIVES: To investigate the influence of propranolol on ventricular remodeling induced by exposure to tobacco smoke. METHODS: Rats were divided into three groups: 1) C, n=10 - control group; 2) F, n=10 - animals exposed to tobacco smoke; 3) BB, n=10 - animals receiving propranolol and exposed to tobacco smoke (40 mg/kg/day). After 2 months, the animals underwent echocardiographic and morphometric analyses. One-way ANOVA (mean ± standard deviation) or the Kruskal-Wallis test (median and interquartile interval) was used. RESULTS: Group BB showed a lower heart rate than group F (C = 358 ± 74 bpm, F = 374 ± 53 bpm, BB = 297 ± 30; P = 0.02). Group F showed greater end-diastolic diameters (C = 18.6 ± 3.4 mm/kg, F = 22.8 ± 1.8 mm/kg, BB = 21.7 ± 1.8 mm/kg; P = 0.003) and left ventricular (LV) end-systolic diameters (C = 8.6 ± 2.1 mm/kg, F = 11.3 ± 1.3 mm/kg, BB = 9.9 ± 1.2 mm/kg; P = 0.004), adjusted for body weight (BW) and a tendency towards a lower ejection fraction (C = 0.90 ± 0.03, F = 0.87 ± 0.03, BB =0.90 ± 0.02; P = 0.07) than group C. Group BB showed a tendency towards a lower LV/BW ratio than group F (C = 1.94 (1.87 - 1.97), F = 2.03 (1.9-2.1) mg/g, BB = 1.89 (1.86-1.94); P = 0.09). CONCLUSION: Administration of propranolol attenuated some of the variables of ventricular remodeling induced by the exposure to tobacco smoke in rats.

FUNDAMENTO: Aún se desconoce el rol del sistema adrenérgico en la remodelación inducida por el tabaquismo. OBJETIVO: Investigar la influencia del propranolol en la remodelación inducida por la exposición al humo del cigarrillo. MÉTODOS: Se dividieron las ratas en tres grupos: 1) C, n=10 - animales control; 2) F, n=10 - animales expuestos al humo de cigarrillo; 3) BB, n=10 - animales expuestos al humo de cigarrillo y que recibieron propranolol (40 mg/kg/día). Tras dos meses, los animales fueron sometidos a estudio ecocardiográfico y morfométrico. Se empleó el análisis de varianza (ANOVA) de una vía (promedio ± desviación estándar) o Kruskal-Wallis (mediana e intervalo intercuartil). RESULTADOS: El Grupo BB presentó menor frecuencia cardiaca que el Grupo F (C = 358 ± 74 lpm, F = 374 ± 53 lpm, BB = 297 ± 30; P = 0,02). El Grupo F presentó mayores diámetros diastólicos (C = 18,6 ± 3,4 mm/kg, F = 22,8 ± 1,8 mm/kg, BB = 21,7 ± 1,8 mm/kg; P = 0,003) y sistólicos (C = 8,6 ± 2,1 mm/kg, F = 11,3 ± 1,3 mm/kg, BB = 9,9 ± 1,2 mm/kg; P = 0,004) del ventrículo izquierdo (VI), ajustado al peso corporal (PC) y tendencia de menor fracción de eyección (C = 0,90 ± 0,03, F = 0,87 ± 0,03, BB =0,90 ± 0,02; P = 0,07) que el Grupo C. El Grupo BB presentó tendencia de menor relación VI/PC que el Grupo F (C = 1,94 (1,87 - 1,97), F = 2,03 (1,9-2,1) mg/g, BB = 1,89 (1,86-1,94); P = 0,09). CONCLUSIÓN: La administración de propranolol atenuó algunas variables de la remodelación ventricular inducida por la exposición al humo del cigarrillo en ratas.

Scurvy induced by obsessive-compulsive disorder.

Historically, scurvy has been associated with sailors of great navigational epochs. This disease has been known since ancient Egypt, but nowadays it is almost forgotten. Although its prevalence has decreased over the centuries, scurvy is still present in developed countries. A 61-year-old man was referred to hospital with a 30-day history of anorexia, fatigue, gingival bleeding and ecchymosis of the arms and legs. On physical examination he presented gingival hypertrophic lesions, signs of chronic periodontitis and petechial rash, and several bruises on his arms and legs. A food frequency questionnaire revealed a long history of poor diet, with no vegetables or fruit. The patient had ingested only chocolate milk and cookies for the last 10 years due to fear of pesticides being present in foods of vegetable origin. A diagnosis of scurvy induced by obsessive-compulsive disorder was suspected, and after vitamin C supplementation there was a marked improvement of symptoms.

The role of oxidative stress and lipid peroxidation in ventricular remodeling induced by tobacco smoke exposure after myocardial infarction

OBJECTIVE: To evaluate the roles of oxidative stress and lipid peroxidation in the ventricular remodeling that is induced by tobacco smoke exposure after myocardial infarction. METHODS: After induced myocardial infarction, rats were allocated into two groups: C (control, n=25) and ETS (exposed to tobacco smoke, n=24). After 6 months, survivors were submitted to echocardiogram and biochemical analyses. RESULTS: Rats in the ETS group showed higher diastolic (C = 1.52 ± 0.4 mm2, ETS = 1.95 ± 0.4 mm2; p=0.032) and systolic (C = 1.03 ± 0.3, ETS = 1.36 ± 0.4 mm2/g; p=0.049) ventricular areas, adjusted for body weight. The fractional area change was smaller in the ETS group (C = 30.3 ± 10.1 %, ETS = 19.2 ± 11.1 %; p=0.024) and E/A ratios were higher in ETS animals (C = 2.3 ± 2.2, ETS = 5.1 ± 2.5; p=0.037). ETS was also associated with a higher water percentage in the lung (C = 4.8 (4.3-4.8), ETS = 5.5 (5.3-5.6); p=0.013) as well as higher cardiac levels of reduced glutathione (C = 20.7 ± 7.6 nmol/mg of protein, ETS = 40.7 ± 12.7 nmol/mg of protein; p=0.037) and oxidized glutathione (C = 0.3 ± 0.1 nmol/g of protein, ETS = 0.9 ± 0.3 nmol/g of protein; p=0.008). No differences were observed in lipid hydroperoxide levels (C = 0.4 ± 0.2 nmol/mg of tissue, ETS = 0.1 ± 0.1 nmol/mg of tissue; p=0.08). CONCLUSION: In animals exposed to tobacco smoke, oxidative stress is associated with the intensification of ventricular remodeling after myocardial infarction.

Exposure time and ventricular remodeling induced by tobacco smoke exposure in rats.

BACKGROUND: We investigated the effects of length of exposure to tobacco smoke on the cardiac remodeling process induced by exposure to cigarette smoke in rats. MATERIAL/METHODS: Rats were separated into 4 groups: nonsmoking (NS)2 (n=25; control animals not exposed to tobacco smoke for 2 months), smoking (S)2 (n=22; rats exposed to smoke from 40 cigarettes/d for 2 months), NS6 (n=18; control animals not exposed to tobacco smoke for 6 months), and S6 (n=25; rats exposed to smoke from 40 cigarettes/d for 6 months). All animals underwent echocardiographic, isolated heart, and morphometric studies. Data were analyzed with a 2-way analysis of variance. RESULTS: No interaction among the variables was found; this suggests that length of exposure to tobacco smoke did not influence the effects of exposure to smoke. Values for left ventricular diastolic diameter/body weight and left atrium/body weight were higher (p=0.023 and p=0.001, respectively) in smoking (S2 and S6) than in nonsmoking animals (NS2 and NS6). Left ventricular mass index was higher (p=0.048) in smoking than in nonsmoking animals. In the isovolumetrically beating ventricle, peak systolic pressure was higher (p=0.034) in smoking than in nonsmoking animals. Significantly higher values were found for left ventricular weight (p=0.017) and right ventricular weight (p=0.001) adjusted for body weight in smoking as opposed to nonsmoking animals. Systolic pressure was higher (p=0.001) in smoking (128+/-14 mm Hg) than in nonsmoking animals (112+/-11 mm Hg). CONCLUSIONS: Length of exposure to cigarette smoke did not influence cardiac remodeling caused by exposure to smoke in rats.

Heart failure due to right ventricular metastatic neuroendocrine tumor.

We report a case of a female patient that was referred to our service with progressive weakness and dyspnea. Three years ago, she had been submitted to hysterectomy and salpingo-oforectomy followed by adjuvant radiotherapy due to uterine cervix neuroendocrine tumor. Two-dimensional echocardiography showed a dense sessile mass in the right ventricle causing right and left ventricular filling restriction. Despite chemotherapy the patient died and necropsy confirmed metastases from neuroendocrine tumor to the right ventricle.

Remodelaçao cardíaca induzida pelo tabagismo (tabaquismo) / Potential mechanisms of cardiac remodeling induced by tobacco

Estudos prévios realizados por nosso grupo mostraram que a exposição à fumaça (humo) do cigarro resulta em remodelação cardíaca com prejuizo da função ventricular. Os mecanismos envolvidos nesse fenômeno entretanto, não são conhecidos. Assim, nosso laboratório tem procurado (buscado) identificar os potenciais mecanismos responsáveis pelo processo de remodelação desencadeado pelo fumo (desencadenado por el acto de fumar). O aumento da pressão (presión) arterial, o sistema renina-angiotensina e o estresse oxidativo podem modular esse processo. Por outro lado, a ativação das MMP-2 ou MMP-9 bem como a lipoperoxidação, não parecem participar das alterações morfológicas e funcionais cardíacas induzidas pelo tabagismo

Remodelaþao cardíaca induzida pelo tabagismo (tabaquismo) / Potential mechanisms of cardiac remodeling induced by tobacco

Estudos prévios realizados por nosso grupo mostraram que a exposiþÒo O fumaþa (humo) do cigarro resulta em remodelaþÒo cardíaca com prejuizo da funþÒo ventricular. Os mecanismos envolvidos nesse fen¶meno entretanto, nÒo sÒo conhecidos. Assim, nosso laboratório tem procurado (buscado) identificar os potenciais mecanismos responsáveis pelo processo de remodelaþÒo desencadeado pelo fumo (desencadenado por el acto de fumar). O aumento da pressÒo (presión) arterial, o sistema renina-angiotensina e o estresse oxidativo podem modular esse processo. Por outro lado, a ativaþÒo das MMP-2 ou MMP-9 bem como a lipoperoxidaþÒo, nÒo parecem participar das alteraþ§es morfológicas e funcionais cardíacas induzidas pelo tabagismo (AU)

Tobacco smoke-induced left ventricular remodelling is not associated with metalloproteinase-2 or -9 activation.

AIM: To investigate the role of MMP-2 and MMP-9 in cardiac remodelling induced by tobacco smoke exposure in rats. METHODS: Rats were allocated into two groups: C (n=9): control animals; ETS (n=9): exposed to tobacco smoke. After 4months, the animals underwent echocardiography, morphometric study and determination of MMP-2 and MMP-9 activity. RESULTS: ETS rats had larger diastolic (C=15.6 +/-1.2 mm/kg, ETS=18.0+/-0.9 mm/kg; p < 0.001) and systolic (C=7.3+/-1.2 mm/kg, ETS=9.2+/-0.9 mm/kg; p=0.001) ventricular diameters adjusted for body weight. Fractional shortening (C=53+/-4.8%, ETS=48+/- 3.3%; p=0.031) and ejection fraction (C=0.89+/-0.03, ETS=0.86+/-0.02; p=0.030) were smaller in the ETS group. Myocyte cross-sectional area (C=245+/-8 microm2, ETS=253+/-8 microm2; p=0.028) was higher in ETS rats. There were no differences in MMP-2 (C=50+/-14%; ETS=43+/-11%, p=0.228) or MMP-9 (C=0.36+/-0.3%; ETS=0.62+/-0.3%, p=0.630) activity between the groups. CONCLUSION: MMP-2 and MMP-9 did not participate in the remodelling process induced by tobacco smoke exposure.

Effects of beta-carotene and smoking on heart remodeling after myocardial infarction.

OBJECTIVE: To analyze the effects of beta-carotene on the ventricular remodeling process following myocardial infarction (MI) in rats exposed to cigarette smoke. METHODS: After acute myocardial infarction (AMI), the animals were divided into four groups: 1) Group C, 24 animals that were given standard diet; 2) Group BC, 26 animals that were given beta-carotene; 3) Group ECS, 26 animals that were given standard diet and were exposed to cigarette smoke; and 4) Group BC+ECS, 20 animals that were given beta-carotene and were exposed to cigarette smoke. After six months, a morphofunctional study was performed. We used a 5% significance level. RESULTS: As regards diastolic areas (DA) and systolic areas (SA), the values for the BC group were higher than those for the C group. If DA/body weight (BW) and SA/BW are considered, the values for group BC+ECS were higher than the values for group C. As regards the fractional area change, we observed significant differences between ECS (lower values) and C (higher values) and between BC (lower values) and C (higher values). Differences between groups regarding infarction size were not observed. The ECS group presented higher values for myocyte cross-section area (MCA) than control animals. Additionally, the BC+ECS group presented higher MCA values than the BC, ECS and C groups. CONCLUSION: After myocardial infarction, smoking and beta-carotene intensified the heart remodeling process; harmful effects of the remodeling process were heightened when the two treatments were used in conjunction.