Spironolactone effects on myocardium changes induced by thyroid hormone in rats / Efeitos da espironolactona sobre as alterações miocárdicas induzidas pelo hormônio tireoideano em ratos

FUNDAMENTO: Estudar o papel do sistema renina-angiotensina-aldosterona na hipertrofia miocárdica induzida pelo hormônio tireoideano, utilizando-se a espironolactona. OBJETIVO: Analisar as alterações morfológicas no miocárdio induzidas pelo hormônio tireoideano e os efeitos da espironolactona nesse processo. MÉTODOS: Foram estudados 40 ratos Wistar, divididos em quatro grupos, que receberam: veículo utilizado para a diluição do hormônio tireoideano (C); levotiroxina sódica (50 µg/rato/dia) (H); espironolactona (0,3 mg/kg/dia) (E) e hormônio tireoideano + espironolactona (HE), nas mesmas doses citadas, durante 28 dias consecutivos. Todos os animais foram submetidos a pesagem, coleta de sangue para dosagens hormonais e realização de ECG no início e no final do experimento. Ao final do período de estudo, os animais foram sacrificados para determinação do peso do ventrículo esquerdo (VE) e obtenção de cortes de VE para análise morfológica. RESULTADOS: Houve aumento dos níveis de T3 no plasma, perda de peso corporal e aumento da freqüência cardíaca nos animais que receberam o hormônio. O peso do VE foi maior nos grupos H e HE. A análise histométrica mostrou maiores diâmetros dos miócitos no grupo H, com os valores decrescentes nos grupos HE, E e C, sendo as diferenças estatisticamente significantes entre todos os grupos. A espironolactona associada ao hormônio tireoideano (HT) diminuiu em 14,6 por cento a hipertrofia transversal dos miócitos. CONCLUSÃO: Em ratos tratados com hormônio tireoideano ocorre hipertrofia cardíaca com aumento do peso do VE e do diâmetro do miócito. A associação de espironolactona ao hormônio tireoideano previne parcialmente essa hipertrofia por mecanismos ainda desconhecidos.

BACKGROUND: To study the possible role of aldosterone on thyroid hormone-induced myocardium hypertrophy, using spironolactone. OBJECTIVE: To evaluate morphological changes in the myocardium induced by thyroid hormone and the possible effects of spironolactone use on these alterations. METHODS: Forty Wistar rats were studied. The animals were allocated to four groups and were given: the vehicle used for dilution of the thyroid hormone (C); sodium levothyroxin at 50 µg/rat/day (H); spironolactone, 0.3 mg/kg/day (S); or thyroid hormone plus spironolactone (HS), at the same doses mentioned above, for 28 consecutive days. All the animals were weighed, had blood drawn for hormonal measurements and underwent ECG at the start and the end of the experiment. At the end of experiment all animals were euthanized, the weight of the left ventricle (LV) was determined and LV slices were obtained for morphological analysis. RESULTS: There was an increase in T3 levels, decrease of body weight and higher heart rate in the animals from group H. The LV weight was significantly higher in the H e HS groups. The histometric analyses that measured the diameter of the myocytes showed higher values in group H and a progressive decrease in groups HS, S and C, with a significant difference among all the groups. The addition of spironolactone decreased the transversal myocyte hypertrophy by 14.6 percent. CONCLUSION: Rats treated with thyroid hormone present cardiac hypertrophy with increased LV weight and greater myocyte diameter. Spironolactone, when associated with thyroid hormone, can partially prevent this hypertrophy through mechanisms that are yet to be determined.

O bloqueio da síntese do óxido nítrico promove aumento da hipertrofia e da fibrose cardíaca em ratos submetidos a treinamento aeróbio / Nitric oxide synthesis blockade increases hypertrophy and cardiac fibrosis in rats submitted to aerobic training

OBJETIVO: O presente estudo avaliou as adaptações teciduais cardíacas em ratos submetidos a treinamento aeróbio, após o bloqueio da síntese de óxido nítrico (NO). MÉTODOS: Os animais (n = 48) foram divididos em quatro grupos: sedentários (grupo CONTROLE), hipertensos após administração de Ng-nitro-L-arginina metil éster durante sete dias (grupo L-NAME), treinados por meio de natação durante oito semanas (grupo TREINADO) e treinados e tratados com L-NAME na última semana (grupo TREINADO L-NAME). Em todos os animais foi registrada a pressão arterial (PA) e realizada a avaliação morfométrica cardíaca. RESULTADOS: Os grupos L-NAME e TREINADO L-NAME apresentaram-se hipertensos em relação aos demais (p < 0,05), porém a elevação da PA no grupo TREINADO L-NAME foi significativamente menor em relação ao L-NAME (p < 0,05). Os grupos TREINADO e TREINADO L-NAME apresentaram índice de peso cardíaco maior que os grupos CONTROLE e L-NAME (p < 0,05). Também apresentaram maiores índices de área cardíaca macroscópica e de fibrose cardíaca em relação aos demais (p < 0,05) e, quando comparados, o grupo TREINADO L-NAME mostrou-se significativamente superior (p < 0,05). CONCLUSÃO: O bloqueio a curto prazo da síntese de NO, em animais sedentários, induziu hipertensão, sem no entanto causar hipertrofia cardíaca. Nos animais treinados, a inibição da síntese de NO atenuou a hipertensão e promoveu hipertrofia cardíaca com aumento expressivo da fibrose miocárdica, sugerindo importante papel do NO nas adaptações teciduais cardíacas induzidas pelo treinamento físico aeróbio.

OBJECTIVE: The objective of the present study was to evaluate cardiac tissue adaptations in rats submitted to aerobic training after nitric oxide (NO) synthesis blockade. METHODS: The animals (n=48) were divided into four groups: sedentary (CONTROL group); hypertensive after administration of NG-nitro-L-arginine methyl ester for 7 days (L-NAME Group); trained for 8 weeks through swimming exercises (TRAINED Group);trained and treated with L-NAME during the last week (L-NAME TRAINED Group). All the animals were submitted to the experiment procedures for blood pressure (BP) readings and cardiac morphometric evaluation. RESULTS: In comparison to the other groups, the L-NAME and L-NAME TRAINED groups were hypertensive (p<0.05); however, BP elevation in the L-NAME TRAINED group was significantly lower than the L-NAME group (p<0.05). The heart weight indexes for the TRAINED and L-NAME TRAINED groups were higher than the CONTROL and L-NAME groups (p<0.05). Also they had presented higher rates of macroscopic cardiac area and cardiac fibrosis in relation to the rest (p<0.05); comparisons revealed that the values for the L-NAME TRAINED group were significantly higher (p<0.05) than the others. CONCLUSION: Short term NO synthesis blockade in sedentary animals induced hypertension but did not cause cardiac hypertrophy. In the trained animals, the inhibition of NO synthesis attenuated hypertension, induced cardiac hypertrophy and significantly increased myocardial fibrosis, indicating that NO plays an important role in cardiac tissue adaptations caused by aerobic exercise.

Aspectos morfológicos produzidos pelo enalaprilato no miocárdio, diagrama e gastrocnêmio induzidos pelo isoproterenol / Morphological aspects produced by isoproterenol-induced enalaprilat in the myocardium, diaphragm and gastrocnemius muscle of rats

Objetivo: Avaliar o efeito do enalaprilato, inibidor da enzima conversorade angiotensina, no processo de reversão da hipertrofia, uma vez quea hipertrofia ventricular esquerda é um importante fator fisiológicopreditivo que auxilia na prevenção de doenças cardíacas, pois seusmecanismos indutores estão relacionados ao índice de massa corporal,hipertensão, hipercolesterolemia, tabagismo, diabetes e uso demedicação, que são empregados nos índices para modelos de avaliaçãode risco. Métodos: Um modelo histomorfométrico comparativo foiempregado para analisar os miócitos do ventrículo esquerdo, diafragmae gastrocnêmio. Oitenta ratos Wistar foram divididos em cinco grupos:controle, isoproterenol, enalaprilato, isoproterenol-enalaprilato (ISOE)e isoproterenol-água. O coração, o diafragma e o gastrocnêmioforam submetidos a uma análise histomorfométrica microscópica.Resultados: A proporção da massa tecidual úmida-seca verificouseaumentada entre os grupos controle e isoproterenol. Não houvediferença estatística significativa ou morfológica entre os demaisgrupos experimentais. Conclusão: Sugere-se que há forte evidênciade que a hipertrofia ventricular esquerda seja primariamente induzidapor ativadores neuro-humorais relacionados aos sistemas simpáticoe renina-angiotensina. O enalaprilato aumenta a taxa de regressãohipertrófica no ventrículo esquerdo, mas isto não é observado nodiafragma e gastrocnêmio.

Electrocardiographic abnormalities among arsenic-exposed persons through groundwater in Bangladesh.

This study was carried out among arsenic-exposed and non-exposed people of Bangladesh to assess and compare their cardiac status based on electrocardiographic (ECG) findings. For the purpose of the study, participants were included in three groups: arsenic-exposed persons with arsenicosis (arsenicosis group), arsenic-exposed persons without arsenicosis (non-arsenicosis group), and persons not exposed to arsenic (non-exposed group). Each group included 50 respondents. In this study, no significant difference in heart rate, rhythm, axis, and pulse rate interval was detected among the arsenicosis, non-arsenicosis and non-exposed groups. A significant difference in corrected QT interval between the arsenicosis and the non-exposed group (p<0.05) was observed. On the contrary, no statistically significant difference in corrected QT interval between the non-arsenicosis and the non-exposed group was found. Abnormal QRS complex was found among 14%, 8%, and 2% of the arsenicosis, non-arsenicosis, and non-exposed groups respectively. ECG findings, indicative of left ventricular hypertrophy, ischaemic heart disease, and right bundle branch block, were high among the arsenicosis group. Overall, abnormal ECG findings were high (58%) among the respondents of the arsenicosis group and were highly significant (p<0.001). The findings revealed that there was a significant association between ECG abnormalities and arsenic exposure.

Analisis ecocardiografico del efecto de diferentes inhibidores del intercambiador Na+/H+ sobre la estructura y funcion sistolica del ventriculo izquierdo en ratas espontaneamente hipertensas / Echocardiographic analysis of the effect of different Na+/H+ exchanger inhibitors on left

El presente estudio fue proyectado para analizar mediante ecocardiograma los efectos del HOE 642 (cariporide) (HOE) y del BIIB 723 (BIIB) sobre la estructura y función sistólica del ventrículo izquierdo en ratas espontáneamente hipertensas (SHR)- 8 con 30 mg/kg/día de HOE, 8 con 30 mg/kg/día de BIIB durante 30 días y 4 sin tratamiento (grupo control) durante esos 30 días. Los distintos parámetros analizados no mostraron cambios durante ese período en las ratas controles. Si bien el HOE determinó un leve descenso de la presión arterial (C: 184 ± 1.75 mm Hg; 30d:176.20 ± 2.60 mm Hg, p <0.01), no detectada con BIIB,ambas drogas provocaron un aumento del estrés sistólico pico (HOE C:166 ± 29 kdinas/cm2; 30d: 204 ± 34kdinas/cm2, p <0.04. BIIB C: 164 ± 25.90 kdinas/cm2; 30d: 234 ± 29.30 kdinas/cm2, p<0.02).Tanto HOE comoBIIB redujeron significativamente la masa ventricular izquierda (MVI) (HOE C: 612.50±50 mg; 30d:452 ± 37 mg,p <0.01; BIIB C: 544 ± 16mg; 30 d: 374 ± 25 mg, p<0.01). El porcentaje de acortamiento endocárdico no semodificó luego del tratamiento con HOE (C: 62.30 ± 2.75; 30d 65.50 ± 2.40%, ns) y BIIB (C: 63.20 ± 2.39%;30d 67.20 ± 1.62%, ns). Los resultados analizados permiten concluir que ambos inhibidores determinaron similarreducción de la MVI. Esa reducción se acompañó de mejoría en los índices de evaluación de la función sistólica ventricular izquierda, pese al incremento del estrés sistólico pico. Estas evidencias sugieren que independientemente del inhibidor utilizado se encuentra un aumento del inotropismo, previamente comprometidodurante el desarrollo de la hipertrofia

The aim of this study was to analyze by echocardiogram, the action of two Na+/H+ exchange, inhibitors, HOE 642 (HOE) and BIIB 723 (BIIB) on left ventricular (LV) mass and LV systolic function. We studied 16 spontaneously hypertensive rats (SHR), 8 treated with HOE 30 mg/kg/day, 8 with 30 mg/kg/day of BIIB during 30 days and 4 SHR as controls during those 30 days. Results are expressed as mean values ± SEM. The systolic blood pressure and theechocardiograpic parameters examined did not evidence changes during that period in the controls rats. Eventhough HOE determined a slight decrease in blood pressure (HOE C: 184 ± 1.75 mm Hg; HOE 30d: 176.20 ±2.60 mm Hg - p <0.01) which was not detected with BIIB, both drugs provoked an increase of peak systolic stress (HOE C: 166 ± 29 kdynes/cm2; HOE 30d: 204 ± 34 kdynes/cm2, p <0.04; BIIB C: 164 ± 25.90 kdynes/cm2; BIIB 30d: 234 ± 29.30 kdynes/cm2, p <0.02). HOE and BIIB reduced LV mass after 30 days of administration (HOE C: 612.50 ± 50 mg; 30d: 452 ± 37 mg, p <0.01. BIIB C: 544 ± 16mg; 30d: 374 ± 25 mg, p <0.01). LV endocardial shortening was similar independently of the NHE inhibitors used (HOE C: 62.30 ± 2.75%; 30d: 65.50 ± 2.40%, ns. BIIB C: 63.20 ± 2,39%; 30d 67,20 ± 1.62%, ns). These data demonstrate that long-treatment with HOE or BIIB produced similar LV mass regression without changes in endocardial fractional shortening in spite of the increase of peak systolic stress. This finding could represent an increased inotropism previously depressed by the development of hypertrophy

Effects of long-term thyroid hormone suppressive treatment on the cardiac functions.

Long-term effects of thyroid hormone suppressive therapy on the heart were evaluated in 45 patients by non-invasive techniques. Fifteen patients were athyreotic after surgery for differentiated thyroid cancer and 30 had diffuse or nodular goiter. Mean age of the group was 42 +/- 12 years. Twenty-four age- and sex-matched subjects were taken as controls. Mean daily dose of levothyroxine was 158 +/- 36 micrograms. Plasma thyroid stimulating hormone (TSH) levels were within normal range. Mean serum T4 and free T4 were significantly higher (p < 0.001) whereas mean serum T3 and free T3 did not differ from the control levels. Non-invasive cardiac assessment was done by a standard 12 lead electrocardiogram (ECG), ambulatory electrocardiographic (Holter) monitoring and echocardiographic study. Six patients had left ventricular hypertrophy in ECG. Holter monitoring demonstrated a higher average heart rate in patients compared to controls (86 +/- 10 vs 72 +/- 6 beats/min; p < 0.001). Supraventricular premature beats were more frequent in patients than in the control group (98% vs 60%; p < 0.06). Echocardiogram showed an increased left ventricular (LV) mass index in patient group (98 +/- 28 vs 78 +/- 16 gm/m2; p < 0.02). LV systolic function was increased with higher values of fractional shortening (40 +/- 8% vs 34 +/- 6%; p < 0.05) and rate-adjusted velocity of shortening (1.4 +/- 0.12 vs 1.02 +/- 0.16 circumferences/sec; p < 0.01). It is concluded that long-term levothyroxine suppressive therapy has significant effects on the cardiac functions.