Stingless bee propolis, metformin, and their combination alleviate diabetic cardiomyopathy

Abstract Background and aim: Stingless bee propolis, a resinous compound processed by mandibular secretion of stingless bees, is used for maintenance of hygiene and stability of beehives. Research on stingless bee propolis shows therapeutic properties attributed to polyphenols exhibiting antioxidative, antihyperglycemic and antiischemic effect. However, the cardioprotective effect of stingless bee propolis on diabetic cardiomyopathy is unknown. Methods: Adult male Sprague Dawley rats were randomised to five groups: normal group, diabetic group, diabetic given metformin (DM+M), diabetic given propolis (DM+P) and diabetic given combination therapy (DM+M+P) and treated for four weeks. Body weight, fasting blood glucose, food and water intake were taken weekly. At the end of experiment, biomarkers of oxidative damage were measured in serum and heart tissue. Antioxidants in heart tissue were quantified. Part of left ventricle of heart was processed for histological staining including Haematoxylin and Eosin (H&E) stain for myocyte size and Masson's Trichrome (MT) stain for heart fibrosis and perivascular fibrosis. Results: Propolis alleviated features of diabetic cardiomyopathy such as myocyte hypertrophy, heart fibrosis and perivascular fibrosis associated with improvement in antioxidative status. Conclusion: This study reports beneficial effect of propolis and combination with metformin in alleviating histopathological feature of diabetic cardiomyopathy by modulating antioxidants, making propolis an emerging complementary therapy.

Myocardial biopsy of Liwen procedure: representability and etiological diagnostic value of cardiac samples obtained by a novel technique in patients with hypertrophic cardiomyopathy / 中华心血管病杂志

Objective: To investigate the representability and etiological diagnostic value of myocardium samples obtained from patients with hypertrophic cardiomyopathy (HCM) by transthoracic echocardiography-guided percutaneous intramyocardial septal biopsy (myocardial biopsy of Liwen procedure). Methods: This study was a retrospective case-series analysis. Patients with HCM, who underwent myocardial biopsy of Liwen procedure and radiofrequency ablation in Xijing Hospital, Air Force Military Medical University from July to December 2019, were included. Demographic data (age, sex), echocardiographic data and complications were collected through electronic medical record system. The histological and echocardiographic features, pathological characteristics of the biopsied myocardium of the patients were analyzed. Results: A total of 21 patients (aged (51.2±14.5) years and 13 males (61.9%)) were enrolled. The thickness of ventricular septum was (23.3±4.5)mm and the left ventricular outflow tract gradient was (78.8±42.6)mmHg (1 mmHg=0.133 kPa). Eight patients (38.1%) were complicated with hypertension, 1 patient (4.8%) had diabetes, and 2 patients (9.5%) had atrial fibrillation. Hematoxylin-eosin staining of myocardial samples of HCM patients before radiofrequency ablation evidenced myocytes hypertrophy, myocytes disarray, nuclear hyperchromatism, hypertrophy, atypia, coronary microvessel abnormalities, adipocyte infiltration, inflammatory cell infiltration, cytoplasmic vacuoles, lipofuscin deposition. Interstitial fibrosis and replacement fibrosis were detected in Masson stained biopsy samples. Hematoxylin-eosin staining of myocardial samples of HCM patients after radiofrequency ablation showed significantly reduced myocytes, cracked nuclear in myocytes, coagulative necrosis, border disappearance and nuclear fragmentation. Quantitative analysis of myocardial specimens of HCM patients before radiofrequency ablation showed that there were 9 cases (42.9%) with mild myocardial hypertrophy and 12 cases (57.1%) with severe myocardial hypertrophy. Mild, moderate and severe fibrosis were 5 (23.8%), 9 (42.9%) and 7 (33.3%), respectively. Six cases (28.6%) had myocytes disarray. There were 11 cases (52.4%) of coronary microvessel abnormalities, 4 cases (19.0%) of adipocyte infiltration, 2 cases (9.5%) of inflammatory cell infiltration,6 cases (28.5%) of cytoplasmic vacuole, 16 cases (76.2%) of lipofuscin deposition. The diameter of cardiac myocytes was (25.2±2.8)μm, and the percentage of collagen fiber area was 5.2%(3.0%, 14.6%). One patient had severe replacement fibrosis in the myocardium, with a fibrotic area of 67.0%. The rest of the patients had interstitial fibrosis. The myocardial specimens of 13 patients were examined by transmission electron microscopy. All showed increased myofibrils, and 9 cases had disorder of myofibrils. All patients had irregular shape of myocardial nucleus, partial depression, mild mitochondrial swelling, fracture and reduction of mitochondrial crest, and local aggregation of myofibrillary interfascicles. One patient had hypertrophy of cardiomyocytes, but the arrangement of muscle fibers was roughly normal. There were vacuoles in the cytoplasm, and Periodic acid-Schiff staining was positive. Transmission electron microscopy showed large range of glycogen deposition in the cytoplasm, with occasional double membrane surround, which was highly indicative of glycogen storage disease. No deposition of glycolipid substance in lysozyme was observed under transmission electron microscope in all myocardial specimens, which could basically eliminate Fabry disease. No apple green substance was found under polarized light after Congo red staining, which could basically exclude cardiac amyloidosis. Conclusion: Myocardium biopsied samples obtained by Liwen procedure of HCM patients are representative and helpful for the etiological diagnosis of HCM.

Pressure Overload-induced Cardiac Hypertrophy Varies According to Different Ligation Needle Sizes and Body Weights in Mice / A Hipertrofia Cardíaca Induzida por Sobrecarga de Pressão Varia de Acordo com os Diferentes Tamanhos de Agulhas para Ligadura e os Pesos Corporais em Ratos

Abstract Background: The cardiac hypertrophy (CH) model for mice has been widely used, thereby providing an effective research foundation for CH exploration. Objective: To research the effects of CH modeling under abdominal aortic constriction (AAC) using different needles and weights in mice. Methods: Four needles with different external diameters (0.35, 0.40, 0.45, and 0.50 mm) were used for AAC. 150 male C57BL/6 mice were selected according to body weight (BW) and divided into 3 weight levels: 18 g, 22 g, and 26 g (n = 50 in each group). All weight levels were divided into 5 groups: a sham group (n = 10) and 4 AAC groups using 4 ligation intensities (n = 10 per group). After surgery, survival rates were recorded, echocardiography was performed, hearts were dissected and used for histological detection, and data were statistically analyzed, P < 0.05 was considered statistically significant. Results: All mice died in the following AAC groups: 18g/0.35 mm, 22 g/0.35 mm, 26 g/0.35 mm, 22 g/0.40 mm, and 26 g/0.40 mm. All mice with AAC, those ligated with a 0.50-mm needle, and those that underwent sham operation survived. Different death rates occurred in the following AAC groups: 18 g/0.40 mm, 18 g/0.45 mm, 18 g/0.50 mm, 22 g/45 mm, 22 g/0.50 mm, 26 g/0.45 mm, and 26 g/0.50 mm. The heart weight/body weight ratios (5.39 ± 0.85, 6.41 ± 0.68, 4.67 ± 0.37, 5.22 ± 0.42, 4.23 ± 0.28, 5.41 ± 0.14, and 4.02 ± 0.13) were significantly increased compared with those of the sham groups for mice with the same weight levels. Conclusion: A 0.45-mm needle led to more obvious CH than did 0.40-mm and 0.50-mm needles and caused extraordinary CH in 18-g mice.

Resumo Fundamentos: O modelo de hipertrofia cardíaca (HC) para ratos foi amplamente utilizado, proporcionando assim uma base de pesquisa efetiva para a exploração de HC. Objetivo: pesquisar os efeitos do modelamento de HC sob constrição da aorta abdominal (CAA) usando diferentes agulhas e pesos em ratos. Métodos: foram utilizadas quatro agulhas com diâmetros externos diferentes (0,35, 0,40, 0,45 e 0,50 mm) para CAA. Foram selecionados 150 ratos C57BL / 6 machos de acordo com o peso corporal (PC) e divididos em 3 níveis de peso: 18 g, 22 g e 26g (n = 50 em cada grupo). Todos os níveis de peso foram divididos em 5 grupos: um grupo sham (n = 10) e 4 grupos CAA usando 4 intensidades de ligadura (n = 10 por grupo). Após a cirurgia, foram registradas as taxas de sobrevivência, foi realizada ecocardiografia, os corações foram dissecados e utilizados para detecção histológica, e os dados foram analisados estatisticamente, p < 0,05 foi considerado estatisticamente significante. Resultados: Todos os ratos morreram nos seguintes grupos de CAA: 18 g/0,35 mm, 22 g/0,35 mm, 26 g/0,35 mm, 22 g/0,40 mm e 26 g/0,40 mm. Todos os ratos com CAA, aqueles ligados com uma agulha de 0,50 mm, e aqueles que sofreram operação sham sobreviveram. Ocorreram diferentes taxas de mortalidade nos seguintes grupos de CAA: 18 g/0,40 mm, 18 g/0,45 mm, 18 g/0,50 mm, 22 g/45 mm, 22 g/0,50 mm, 26 g/0,45 mm e 26 g/0,50 mm. As proporções de peso do coração/peso corporal (5,39 ± 0,85, 6,41 ± 0,68, 4,67 ± 0,37, 5,22 ± 0,42, 4,23 ± 0,28, 5,41 ± 0,14 e 4,02 ± 0,13) aumentaram significativamente em comparação com os grupos sham para ratos com os mesmos níveis de peso. Conclusão: uma agulha de 0,45mm levou a HC mais óbvia do que as agulhas de 0,40 mm e 0,50mm e causou HC extraordinária em ratos de 18 g.

Base of the skull morphology and Class III malocclusion in patients with unilateral cleft lip and palate

OBJECTIVE: The aim of the present study was to determine the morphological differences in the base of the skull of individuals with cleft lip and palate and Class III malocclusion in comparison to control groups with Class I and Class III malocclusion. METHODS: A total of 89 individuals (males and females) aged between 5 and 27 years old (Class I, n = 32; Class III, n = 29; and Class III individuals with unilateral cleft lip and palate, n = 28) attending PUC-MG Dental Center and Cleft Lip/Palate Care Center of Baleia Hospital and PUC-MG (CENTRARE) were selected. Linear and angular measurements of the base of the skull, maxilla and mandible were performed and assessed by a single calibrated examiner by means of cephalometric radiographs. Statistical analysis involved ANCOVA and Bonferroni correction. RESULTS: No significant differences with regard to the base of the skull were found between the control group (Class I) and individuals with cleft lip and palate (P > 0.017). The cleft lip/palate group differed from the Class III group only with regard to CI.Sp.Ba (P = 0.015). Individuals with cleft lip and palate had a significantly shorter maxillary length (Co-A) in comparison to the control group (P < 0.001). No significant differences were found in the mandible (Co-Gn) of the control group and individuals with cleft lip and palate (P = 1.000). CONCLUSION: The present findings suggest that there are no significant differences in the base of the skull of individuals Class I or Class III and individuals with cleft lip and palate and Class III malocclusion. .

OBJETIVO: o objetivo do presente estudo foi determinar diferenças morfológicas da base do crânio de indivíduos portadores de fissura de lábio e palato e de má oclusão de Classe III, comparado-os com indivíduos controle com má oclusão de Classes I ou III. MÉTODOS: oitenta e nove indivíduos, de ambos os sexos, com idade variando entre 5 e 27 anos, Classe I (n = 32), Classe III não fissurados (n = 29) e Classe III com fissura labiopalatina unilateral (n = 28), oriundos do Centro de Odontologia e Pesquisa da PUC-MG e do Centro de Atendimento de Fissurados do Hospital da Baleia e da PUC-MG (CENTRARE), foram selecionados. Medições lineares e angulares da base do crânio, maxila e mandíbula foram realizadas e avaliadas por um único examinador calibrado, por meio de radiografias cefalométricas. Foram utilizados os testes ANCOVA e correção de Bonferroni para a análise estatística dos dados. RESULTADOS: com relação à base do crânio, os resultados não indicaram diferença estatística entre indivíduos controle (Classe I) e os indivíduos com fissuras (p > 0,017). O grupo com fissura foi diferente do grupo Classe III somente em relação à medida CI.Sp.Ba (p = 0,015). O comprimento maxilar (Co-A) apresentou diferença estatisticamente significativa na comparação entre o grupo controle (Classe I) e o grupo com fissuras (p < 0,001), sendo que os fissurados apresentaram uma maxila menor. Não foram encontradas diferenças na mandíbula (Co-Gn) entre indivíduos do grupo controle (Classe I) e indivíduos fissurados (p = 1,000). CONCLUSÃO: os resultados sugerem que não houve diferença estatisticamente significativa na base do crânio entre indivíduos Classe I e III e indivíduos com fissuras de lábio e palato com má oclusão de Classe III. .

The role of Ca2+/calmodulin-dependent protein kinase II and calcineurin in TNF-α-induced myocardial hypertrophy

We investigated whether Ca2+/calmodulin-dependent kinase II (CaMKII) and calcineurin (CaN) are involved in myocardial hypertrophy induced by tumor necrosis factor α (TNF-α). The cardiomyocytes of neonatal Wistar rats (1-2 days old) were cultured and stimulated by TNF-α (100 μg/L), and Ca2+ signal transduction was blocked by several antagonists, including BAPTA (4 µM), KN-93 (0.2 µM) and cyclosporin A (CsA, 0.2 µM). Protein content, protein synthesis, cardiomyocyte volumes, [Ca2+]i transients, CaMKIIδB and CaN were evaluated by the Lowry method, [³H]-leucine incorporation, a computerized image analysis system, a Till imaging system, and Western blot analysis, respectively. TNF-α induced a significant increase in protein content in a dose-dependent manner from 10 µg/L (53.56 µg protein/well) to 100 μg/L (72.18 µg protein/well), and in a time-dependent manner from 12 h (37.42 µg protein/well) to 72 h (42.81 µg protein/well). TNF-α (100 μg/L) significantly increased the amplitude of spontaneous [Ca2+]i transients, the total protein content, cell size, and [³H]-leucine incorporation in cultured cardiomyocytes, which was abolished by 4 µM BAPTA, an intracellular Ca2+ chelator. The increases in protein content, cell size and [³H]-leucine incorporation were abolished by 0.2 µM KN-93 or 0.2 µM CsA. TNF-α increased the expression of CaMKIIδB by 35.21% and that of CaN by 22.22% compared to control. These effects were abolished by 4 µM BAPTA, which itself had no effect. These results suggest that TNF-α induces increases in [Ca2+]i, CaMKIIδB and CaN and promotes cardiac hypertrophy. Therefore, we hypothesize that the Ca2+/CaMKII- and CaN-dependent signaling pathways are involved in myocardial hypertrophy induced by TNF-α.

Remodelamento cardíaco: análise seriada e índices de detecção precoce de disfunção ventricular / Cardiac remodeling: serial analysis and indexes for early detection of ventricular dysfunction / Remodelación cardiaca: análisis seriado e índices de detección precoz de disfunción ventricular

Fundamento: A estenose aórtica supravalvar (EAo) é utilizada para o estudo da remodelação cardíaca (RC) por sobrecarga pressórica. Nesse modelo, não estão claramente estabelecidos o comportamento da RC desde a fase inicial, nem os melhores parâmetros para a identificação da disfunção ventricular. OBJETIVOS: 1) Caracterizar, precoce e evolutivamente, as modificações morfofuncionais durante a RC em ratos com EAo e 2) identificar o índice mais sensível para detecção do momento do aparecimento da disfunção diastólica e sistólica do ventrículo esquerdo (VE). Métodos: Ratos Wistar foram divididos em dois grupos - controle (GC, n=13) e EAo (GEAo, n=24) - e estudados nas 3ª, 6ª, 12ª e 18ª semanas pós-cirurgia. Os corações foram analisados por meio de ecocardiograma (ECO). Resultados: Ao final do experimento, as relações do VE, do ventrículo direito e dos átrios com o peso corporal final foram aumentadas no GEAo. O ECO mostrou que o átrio esquerdo sofreu uma remodelação significativa a partir da 6ª semana. No GEAo, a porcentagem de encurtamento endocárdico apresentou queda significativa a partir da 12ª semana e a porcentagem de encurtamento mesocárdico, na 18ª semana. A relação onda E e onda A (E/A) foi superior no GC em comparação ao GEAo em todos os momentos analisados. Conclusões: O ventrículo esquerdo dos ratos com EAo, durante o processo de remodelação, apresentou hipertrofia concêntrica, disfunção diastólica precoce e melhoria da função sistólica, com posterior deterioração do desempenho. Além disso, constatou-se que os índices ecocardiográficos mais sensíveis para a detecção da disfunção diastólica e sistólica são, respectivamente, a relação E/A e a porcentagem de encurtamento endocárdico.

Background: Supravalvar aortic stenosis (SVAS) is used to study overload-induced cardiac remodeling (CR). In this model, neither CR behavior since beginning stage nor the best parameters to identify ventricular dysfunction are clearly stated. Objective: 1) Characterizing, early and evolutively, morphological and functional modifications during CR in rats with SVAS and 2) identifying the most sensitive index for detecting the moment when the diastolic and systolic dysfunction first appeared in the left ventricle (LV). Methods: Wistar Rats were divided into two groups - control (CG, n=13) and SVAS (SVASG, n=24) - and studied in post-surgical 3rd, 6th, 12th and 18th weeks. Hearts were analyzed by means of an echocardiogram (ECHO). Results: By the end of the experiment, ratios between the LV, right ventricle and atria and the final body weight were increased in the SVASG. The ECHO showed that the left atrium underwent significant remodeling from the 6th on. The percent of endocardial shortening underwent significant drop as of the 12nd week and the percent of, as of the 18th week, in the SVASG. The ratio between E- wave and A-wave (E/A) was higher in CG compared to the SVASG in all events analyzed. Conclusions: During the remodeling process, the left ventricle of rats with SVAS presented concentric hypertrophy, early diastolic dysfunction and improvement of systolic function, with posterior performance deterioration. Besides this, the study found out the most sensitive echocardiographic indexes for detecting systolic and diastolic dysfunction are, respectively, the ratio E/A and the percent of endocardial shortening.

Fundamento: La estenosis aórtica supravalvular (EAo) se utiliza para el estudio de la remodelación cardiaca (RC) por sobrecarga de presión. En este modelo, no están claramente establecidos el comportamiento del RC desde la fase inicial, ni los mejores parámetros para la identificación de la disfunción ventricular. OBJETIVO: 1) Caracterizar, precoz y evolutivamente, las modificaciones morfofuncionales durante el RC en ratones con EAo, y 2) identificar el índice más sensible para detección del momento de la aparición de la disfunción diastólica y sistólica del ventrículo izquierdo (VI). Métodos: Ratones Wistar se dividieron en dos grupos - control (GC, n=13) y EAo (GEAo, n=24) - y estudiados en las 3ª, 6ª, 12ª y 18ª semanas post cirugía. Los corazones se analizaron por medio de ecocardiograma (ECO). Resultados: Al final del experimento, las relaciones del VI, del ventrículo derecho y de los atrios con el peso corporal final fueron aumentadas en el GEAo. El ECO mostró que el atrio izquierdo sufrió una remodelación significativa a partir de la 6ª semana. En el GEAo, el porcentaje de acortamiento endocárdico presentó disminución significativa a partir de la 12ª semana y el porcentaje de acortamiento mesocárdico, en la 18ª semana. La relación onda E y onda A (E/A) fue superior en el GC en comparación al GEAo en todos los momentos analizados. Conclusión: El ventrículo izquierdo de los ratones con EAo, durante el proceso de remodelación, presentó hipertrofia concéntrica, disfunción diastólica precoz y mejora de la función sistólica, con posterior deterioro del desempeño. Además de ello, se constató que los índices ecocardiográficos más sensibles para la detección de la disfunción diastólica y sistólica son, respectivamente, la relación E/A y el porcentaje de acortamiento endocárdico.

Hipertensão pulmonar associada à síndrome da imunodeficiência adquirida: apresentação de cinco casos e revisão da literatura / Pulmonary hypertension associated with acquired immunodeficiency syndrome: presentation of five cases and review of the literature

Diversas doenças cardiorespiratórias podem complicar a síndrome da imunodeficiência adquirida. A hipertensão pulmonar é uma rara doença com um pobre prognóstico. Nós descrevemos esta síndrome em cinco pacientes com infecção pelo vírus da imunodeficiência adquirida em nosso serviço com revisão da literatura.

Several cardiorespiratory diseases may complicate the acquired immunodeficiency syndrome. Pulmonary hypertension is a rare clinical disorder with a poor prognosis. We describe this syndrome in five patients seen at our service who presented infection with the acquired immunodeficiency virus, and we review the literature.

Regression of gestational diabetes induced cardiomegaly in offspring of diabetic rat / Regressão da miocardiopatia hipertrófica em filhotes de ratas diabéticas

PURPOSE: To compare body weight and length, heart weight and length, heart-to-body weight ratio, glycemia, and morphometric cellular data of offspring of diabetic rats (ODR) and of normal rats (control). METHODS: Diabetes was induced in 3 pregnant Wistar rats, bearing 30 rats, on the 11th day after conception by intraperitoneal injection of 50 mg/kg of streptozotocin. Six normal pregnant Wistar rats, bearing 50 rats, made up the control group. Morphometric data were obtained using a scale for the weight, length, heart and body measurements. Morphometric cellular data were obtained by a computer assisted method applied to the measurements of myocytes. Statistical analysis utilized Student's t-test, ANOVA and Levene test. RESULTS: Control offspring had greater mean body weight and length than offspring of diabetic rats (p < 0.001). Heart weight and length and heart-to-body ratios of newborn rats differed between groups at birth (p < 0.001), but showed no difference at 21 days. Mean nuclei area and perimetric value of the myocytes decrees throughout the first 21 days of life (p < 0.01) in the diabetic group. CONCLUSIONS: Heart hypertrophy on the offspring of diabetic rats at birth was demonstrated by the significant difference between the groups. After the eleventh day, no difference was found, which confirmed regression of cardiomegaly. The significant difference between the first and the 21th day of life, for nuclei area feature, demonstrate regression of cardiac hypertrophy in the offspring of diabetic rats.

OBJETIVO: Comparar as medidas cardíacas e a morfometria celular miocárdica dos filhotes de ratas diabéticas (FRD) com filhotes de ratas normais (FRN). MÉTODOS: Foram estudados 30 filhotes de 3 ratas Wistar com diabetes gestacional induzido por 50mg/kg de estreptozotocina, no 11° dia após a concepção. O grupo controle foi de 50 filhotes de 6 ratas Wistar normais. As medidas de comprimento, peso corporal e peso cardíaco foram realizadas com paquímetro e balança e as medidas celulares por analisador computadorizado de imagem. A análise estatística usou o Teste t de Student, ANOVA e teste de Levene. RESULTADOS: A média de peso e comprimento dos filhotes, desde o nascimento até os 21 dias de vida, foi significativamente maior (p<0,001) no grupo dos FRN. O peso, tamanho cardíaco e a proporção cardíaca dos FRD, ao nascimento, foi, significativamente, maior (p<0,001), regredindo ao longo dos 21 dias de vida. Os FRD apresentaram uma regressão significativa da área e perímetro nuclear (p<0,01) do nascimento aos 21 dias de vida, o mesmo não ocorrendo no grupo controle. CONCLUSÕES: Os FRD apresentaram, ao nascimento, maior tamanho cardíaco, maior peso cardíaco e maior proporção peso cardíaco-peso corporal do que FRN, havendo igualdade estatística entre os dois grupos a partir do 11° dia de vida. Houve diferença significativa entre o nascimento e o 21º dia de vida nas medidas celulares demonstrando regressão da hipertrofia miocárdica nos filhotes das ratas diabéticas.

Real-time three-dimensional echocardiographic assessment of left ventricular remodeling index in patients with hypertensive heart disease and coronary artery disease / 华中科技大学学报（医学）（英德文版）

Left ventricular remodeling index (LVRI) was assessed in patients with hypertensive heart disease (HHD) and coronary artery disease (CAD) by real-time three-dimensional echocardiography (RT3DE). RT3DE data of 18 patients with HHD, 20 patients with CAD and 22 normal controls (NC) were acquired. Left ventricular end-diastolic volume (EDV) and left ventricular end-diastolic epicardial volume (EDVepi ) were detected by RT3DE and two-dimensional echocardiography Simpson biplane method (2DE). LVRI (left ventricular mass /EDV) was calculated and compared. The results showed that LVRI measurements detected by RT3DE and 2DE showed significant differences inter-groups (P0.05), but significant difference in HHD and CAD intra-group (P0.05). It was concluded that LVRI derived from RT3DE as a new index for evaluating left ventricular remodeling can provide more superiority to LVRI derived from 2DE.

Epigallocatechin-3 gallate prevents cardiac hypertrophy induced by pressure overload in rats

Pressure overload diseases, such as valvular stenosis and systemic hypertension, manifest morphologically in patients as cardiac concentric hypertrophy. Prevention of cardiac remodeling due to increased pressure overload is important to reduce morbidity and mortality. Epigallocatechin-3 gallate (EGCG) is a major bioactive polyphenol present in green tea which has been found to be a nitric oxide-mediated vasorelaxant and to be cardioprotective in myocardial ischemia-reperfusion injury. Therefore, we investigated whether EGCG supplementation could reduce in vivo pressure overloadmediated cardiac hypertrophy. Cardiac hypertrophy was induced by suprarenal transverse abdominal aortic constriction (AC) in rats. Three weeks after AC surgery, heart to body weight ratio increased in the AC group by 34% compared to the sham group. EGCG administration suppressed the load-induced increase in heart weight by 69%. Attenuation of cardiac hypertrophy by EGCG was associated with attenuation of the increase in myocyte cell size and fibrosis induced by aortic constriction. Despite abolition of hypertrophy by EGCG, transstenotic pressure gradients did not change. Echocardiogram revealed that increased left ventricular systolic dimensions and deteriorated systolic function were relieved by EGCG. These results suggest that EGCG prevents the development of left ventricular concentric hypertrophy by pressure overload and may be a useful therapeutic modality to prevent cardiac remodeling in patients with pressure overload myocardial diseases.

Swimming training increases cardiac vagal activity and induces cardiac hypertrophy in rats

The effect of swimming training (ST) on vagal and sympathetic cardiac effects was investigated in sedentary (S, N = 12) and trained (T, N = 12) male Wistar rats (200-220 g). ST consisted of 60-min swimming sessions 5 days/week for 8 weeks, with a 5 percent body weight load attached to the tail. The effect of the autonomic nervous system in generating training-induced resting bradycardia (RB) was examined indirectly after cardiac muscarinic and adrenergic receptor blockade. Cardiac hypertrophy was evaluated by cardiac weight and myocyte morphometry. Plasma catecholamine concentrations and citrate synthase activity in soleus muscle were also determined in both groups. Resting heart rate was significantly reduced in T rats (355 ± 16 vs 330 ± 20 bpm). RB was associated with a significantly increased cardiac vagal effect in T rats (103 ± 25 vs 158 ± 40 bpm), since the sympathetic cardiac effect and intrinsic heart rate were similar for the two groups. Likewise, no significant difference was observed for plasma catecholamine concentrations between S and T rats. In T rats, left ventricle weight (13 percent) and myocyte dimension (21 percent) were significantly increased, suggesting cardiac hypertrophy. Skeletal muscle citrate synthase activity was significantly increased by 52 percent in T rats, indicating endurance conditioning. These data suggest that RB induced by ST is mainly mediated parasympathetically and differs from other training modes, like running, that seems to mainly decrease intrinsic heart rate in rats. The increased cardiac vagal activity associated with ST is of clinical relevance, since both are related to increased life expectancy and prevention of cardiac events.

Low coronary perfusion pressure is associated with endocardial fibrosis in a rat model of volume overload cardiac hypertrophy

No remodelamento que se segue às sobrecargas de volume não é descrito o aumento de fibrose miocárdica. Após o infarto, entretanto, há hipertrofia do miocárdio remoto com acúmulo de fibrose, particularmente no subendocárdio. Na fístula aorto-cava, tal como no infarto, é possível que a queda da pressão de perfusão coronariana interfira com a fibrose cardíaca. OBJETIVO: Investigar o papel das mudanças hemodinâmicas agudas sobre a fibrose cardíaca na fístula aorto-cava. MÉTODO: Ratos Wistar submetidos a fístula aorto-cava, seguidos por 4 e 8 semanas, constituíram 4 grupos, fístula aorto-cava 4 e fístula aorto-cava 8 (10 ratos cada) e seus respectivos controles (sham-operated controls - Sh), Sh4 e Sh8 (8 ratos cada). A hemodinâmica foi realizada 1 semana após a cirurgia. A hipertrofia e a fibrose foram quantificadas ao final do seguimento pelo diâmetro dos miócitos e pela fração de volume do colágeno. RESULTADOS: Comparados com Sh4 e Sh8, a pressão de pulso, a pressão diastólica final do ventrículo esquerdo e a +dP/dt foram maiores em fístula aorto-cava 4 e fístula aorto-cava 8, enquanto a -dP/dt foi similar. A pressão estimada da perfusão coronariana (mmHg) foi menor em fístula aorto-cava 8 (52,6±4,1) do que em Sh8 (100,8±1,3), mas comparável entre fístula aorto-cava 4 (50,0±8,9) e Sh4 (84,8±2,3). O diâmetro dos miócitos foi maior em fístula aorto-cava 8 e a fibrose intersticial e subendocárdica maior em fístula aorto-cava 4 e fístula aorto-cava 8. Houve correlação inversa e independente da pressão de perfusão coronariana com a fibrose subendocárdica (r2=0,86; p<0,0001) e das pressões sistólica (r2=0,73; p=0,0035) e diastólica final do ventrículo esquerdo (r2=0,55; p=0.0124) com a fibrose intersticial. CONCLUSÃO: A queda precoce da pressão de perfusão coronariana e o aumento das pressões ventriculares após a fístula aorto-cava associam-se com fibrose miocárdica subseqüente.

Alteraçöes da matrix extracelular cardíaca na hipertrofia miocárdica / Changes of the extracellular cardiac matrix in the hypertrophied myocardium

A patogênese da maioria das doenças tem sido associada classicamente a alterações que ocorrem nos componentes celulares dos tecidos. Assim, a insuficiência cardíaca tem sido relacionada quase que inteiramente a alterações dos miócitos. Mais recentemente, tem-se observado que modificações da matriz extracelular estão envolvidas em uma série de distúrbios estruturais e funcionais do coração. Dessa forma, o melhor conhecimento da dinâmica da matriz extracelular cardíaca é importante para a melhor compreensão da fisiopatologia de distúrbios da função da bomba cardíaca, como na insuficiência cardíaca diastólica, bem como o fenômeno de remodelamento ventricular observado na hipertensão arterial e após infarto do miocárdio. Neste artigo são revistos os conhecimentos atuais sobre a composição e a dinâmica da matriz extracelular cardíaca, procurando-se enfocar possíveis pontos onde as alterações da matriz possam ser moduladas por meio do uso de drogas. É ressaltado o papel exercido pela angiotensina II na deposição de colágeno que ocorre na fibrose miocárdica reativa da hipertensão arterial e infarto do miocárdio.

El colágeno en el miocardio / Collagen in the myocardium

Los principales adelantos recientes en el estudio de la contractilidad del miocardio son consecuencia del descubrimiento, completado hace muy pocos años, de la existencia de una muy fina red de colágeno perimiocitario, a lo largo del cual se transmite la energía cinética originada por el desplazamiento de las bandas "Z". A su vez este colágeno organiza grupos de células de eje funcional concordante reuniéndolas en paquetes de complejidad jerárquica creciente denominados fibrillas, fibras y fascículos. Queda así definido el fascículo como la unidad morfológica y funcional del tejido contráctil y el colágeno perimiocitario como una estructura indispensable a su efectividad motriz. Conocida la estructura y función de este colágeno intrínseco o motriz ha sido posible entender su participación decisiva en el comportamiento disfuncional del denominado miocardio atontado, del hibernado o del subletalmente isquémico, como en la periferia de áreas necróticas. Muy importante ha sido reconocer que en la hipertrofia cardíaca patológica se alteran, en ambos ventrículos, otras formas de colágeno, distintas del perimiocitario intrínseco. Se trata del colágeno reactivo perivascular e intersticial y del colágeno reparativo o cicatricial, los cuales deterioran notoriamente la función. Sobre ellos es posible actuar farmacológicamente