Atrophic Cardiac Remodeling Induced by Taurine Deficiency in Wistar Rats

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Tobacco Smoke Induces Ventricular Remodeling Associated with an Increase in NADPH Oxidase Activity

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Papel relativo da remodelação geométrica do ventrículo esquerdo, morfológica e funcional do miocárdio na transição da hipertrofia compensada para a falência cardíaca em ratos com estenose aórtica supravalvar

OBJETIVO: Avaliar a contribuição relativa da remodelação geométrica do ventrículo esquerdo (VE) e das alterações morfológicas e funcionais do miocárdio, em ratos com estenose aórtica supravalvar (EAS), na fase de transição da hipertrofia compensada para a insuficiência cardíaca congestiva (ICC). MÉTODOS: Vinte e uma semanas após a indução da EAS os ratos foram classificados como controles (GC,n=13), não portadores (GE,n=11) ou portadores de insuficiência cardíaca congestiva (GE-IC,n=12).Todos os grupos foram avaliados com estudo ecocardiográfico, hemodinâmico e morfológico do miocárdio. RESULTADOS: Vinte e uma semanas após EAS: índice de massa (GE-IC>GE>GC,p<0.05); pressão sistólica: (GE-IC = GE>GC, p<0,05); pressão diastólica: (GE-IC>GE>GC, p<0,05); estresse meridional sistólico e diastólico: (GE-IC>GE>GC,p<0.05); área de secção dos miócitos: (GE-IC>GE>GC, p<0,05) e conteúdo de hidroxiprolina: (GE-IC>GE>GC, p<0,05) do VE. No grupo GE-IC o remodelamento geométrico do VE foi caracterizado por aumento significante das dimensões e espessura relativa da parede normal (remodelamento excêntrico) enquanto que o grupo GE apresentou remodelamento concêntrico. Os índices de desempenho do VE do grupo GE-IC foram significantemente menores que do grupo GE. CONCLUSÃO: Os grupos GE-IC e GE diferiram primariamente no processo de remodelação geométrica do VE e estrutural do miocárdio que estabeleceu um estado cronicamente compensado no grupo GE e precipitou a ICC no grupo GE-IC na vigência de graus equivalentes de comprometimento da contratilidade. Neste modelo experimental a fase de transição da hipertrofia compensada para a ICC está mais estreitamente relacionada com o remodelamento geométrico adverso do VE e estrutural do miocárdio do que com o grau de comprometimento da contratilidade.

Ventricular remodeling induced by retinoic acid supplementation in adult rats

Retinoic acid (RA) plays a role in regulating cardiac geometry and function throughout life. The aim of this study was to analyze the cardiac effects of RA in adult rats. Wistar rats were randomly allocated to a control group (n = 18) receiving standard rat chow and a group treated with RA (n = 14) receiving standard rat chow supplemented with RA for 90 days. All animals were evaluated by echocardiography, isolated papillary muscle function, and morphological studies. Whereas the RA-treated group developed an increase in both left ventricular (LV) mass and LV end-diastolic diameter, the ratio of LV wall thickness to LV end-diastolic diameter remained unchanged when compared with the control group. In the isolated papillary muscle preparation, RA treatment decreased the time to peak developed tension and increased the maximum velocity of isometric relengthening, indicating that systolic and diastolic function was improved. Although RA treatment produced an increase in myocyte cross-sectional area, the myocardial collagen volume fraction was similar to controls. Thus our study demonstrates that small physiological doses of RA induce ventricular remodeling resembling compensated volume-overload hypertrophy in rats.

Partial urethral obstruction of rabbit urinary bladder: stereological evidence that the increase in muscle content is mostly driven by changes in number, rather than size, of smooth muscle cells

The effects of partial urethral obstruction on the detrusor muscle of rabbit urinary bladder were investigated using stereological sampling and estimation tools. Twelve female Norfolk rabbits (2.5-3.0 kg body weight) were divided into four groups: 3, 7 and 12 weeks after surgical intervention to produce a standard partial obstruction and unobstructed controls. Following removal, bladder axes (craniocaudal, dorsoventral and laterolateral) and organ weights were recorded. Bladders were prepared for light microscopy by multistage random sampling procedures. Stereological methods were used to estimate the volume of muscle and the packing density and total number of myocyte nuclei in each bladder. We also estimated mean myocyte volume and the mean cross-sectional area and length of myocytes. Group comparisons were made by one-way analysis of variance. Changes in bladder axes were mainly laterolateral and craniocaudal. Mean bladder weight increased roughly six-fold by 3 weeks and 17-fold by 12 weeks and was accompanied, on average, by 12- and 33-fold increases in total muscle volume. These variables did not differ at 3 and 7 weeks post-obstruction. Increases in muscle content were not accompanied by changes in packing densities but were associated with increases in the total numbers of myocyte nuclei (13-fold by 3 weeks, 28-fold by 12 weeks). Mean myocyte volume did not vary significantly between groups but cells in obstructed groups were shorter and wider. These findings support the notion that partial outflow obstruction leads to an increase in the number, but not mean volume, of myocytes. If due solely to myocyte mitosis, the total of 43 x 10(8) cells found at 12 weeks could be generated by the original complement of 15 x 10(7) cells if an average of only 2.1 x 10(6) new cells was produced every hour. In reality, even this modest proliferation rate is unlikely to be achieved because myocyte proliferation rates are very low and it is possible that new myocytes can arise by differentiation of mesenchymal or other precursor cells.

Swimming training exacerbates pathological cardiac hypertrophy in kinin B(2) receptor-deficient mice

Kallikrein-kinin system exerts cardioprotective effects against pathological hypertrophy. These effects are modulated mainly via B(2) receptor activation. Chronic physical exercise can induce physiological cardiac hypertrophy characterized by normal organization of cardiac structure. Therefore, the aim of this work was to verify the influence of kinin B(2) receptor deletion on physiological hypertrophy to exercise stimulus. Animals were submitted to swimming practice for 5 min or for 60 min, 5 days a week, during 1 month and several cardiac parameters were evaluated. Results showed no significantly difference in heart weight between both groups, however an increased left ventricle weight and myocyte diameter were observed after the 60 min swimming protocol, which was more pronounced in B(2)(-/-) mice. In addition, sedentary B(2)(-/-) animals presented higher left ventricle mass when compared to wild-type (WT) mice. An increase in capillary density was observed in exercised animals, however the effect was less pronounced in B(2)(-/-) mice. Collagen, a marker of pathological hypertrophy, was increased in B(2)(-/-) mice submitted to swimming protocol, as well as left ventricular thickness, suggesting that these animals do not respond with physiological hypertrophy for this kind of exercise. In conclusion, our data suggest an important role for the kinin B(2) receptor in physiological cardiac hypertrophy. (c) 2007 Elsevier B.V. All rights reserved.

Cardiac benefits of exercise training in aging spontaneously hypertensive rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The effect of non-antihypertensive doses of angiotensin converting enzyme inhibitor on myocardial necrosis and hypertrophy in young rats with renovascular hypertension

In renovascular hypertensive rats, low doses of angiotensin converting enzyme (ACE) inhibitors have been found to prevent myocardial hypertrophy independent of blood pressure level. This finding would suggest humoral rather than mechanical control of myocyte growth. The aim of this study was to examine the effect of nonantihypertensive doses of ACE inhibitor on myocardial hypertrophy and necrosis in hypertensive rats. Renovascular hypertension (RHT) was induced in four-week-old Wistar rats. Twenty-eight animals were treated for four weeks with three doses of ramipril (0.01, 0.1 or 1.0 mg/kg/day, which are unable to lower blood pressure. Fourteen animals were not treated (RHT group). A sham operated, age/sex-matched group was used as control (n=10). Myocardial histology was analysed in 3 μm thick sections of the ventricle stained with either haematoxylin-eosin, reticulin silver stain or Masson's trichrome. There was a significant correlation between systolic blood pressure and left ventricular to body weight ratio in both sets of animals: untreated plus controls and ramipril-treated rats. ACE inhibition prevented myocyte and perivascular necrosis and fibrosis in a dose-dependent manner. We conclude that myocardial hypertrophy in rats with renovascular hypertension is directly related to arterial pressure, and that this relationship is not affected by nonantihypertensive doses of ACE inhibitor. Myocardial necrosis/fibrosis and coronary artery damage induced by angiotensin II are prevented by ACE inhibitor in a dose-dependent manner, despite the presence of arterial hypertension.

Retinoic acid supplementation attenuates ventricular remodeling after myocardial infarction in rats

The objective of this study was to evaluate the role of retinoic acid in experimental postinfarction myocardial remodeling. Wistar rats were subjected to myocardial infarction (MI) and treated with retinoic acid (RA), 0.3 mg/(kg · d) (MI-RA, n = 29), or fed a control diet (MI, n = 34). After 6 mo, the surviving rats (MI-RA = 18 and MI = 22) underwent echocardiograms, and isolated hearts were tested for function in vitro. The cross-sectional area of the myocyte (CSA) and interstitial collagen fraction (IC) were measured in a cross section of the heart stained by hematoxylin-eosin and picrosirius red, respectively. The CSA was smaller in the MI-RA group [229 (220, 234) μm 2] [medians (lower quartile, upper quartile)] than in the MI group [238 (232, 241) μm 2] (P = 0.01) and IC was smaller in the MI-RA group [2.4 (1.7, 3.1)%] than in the MI group [3.5 (2.6, 3.9)%] (P = 0.05). The infarct size did not differ between the groups [MI = 44.6 (40.8, 48.4)%, MI-RA = 45 (38.6, 47.2)%]. Maximum rate of rise of left ventricular pressure (+dp/dt) was greater in the MI-RA group (2645 ± 886 mm Hg/s) than in the MI group (2081 ± 617 mm Hg/s) (P = 0.05). The other variables tested did not differ between groups. Retinoic acid supplementation of rats for 6 mo attenuates the ventricular remodeling process after MI. © 2005 American Society for Nutrition.

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 μm2, 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-g or TNF-a 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. © Med Sci Monit, 2010.

Subclinical muscle injuries in dogs infected with Leishmania (Leishmania) infantum chagasi

Although canine visceral leishmaniasis (CVL) has been extensively studied, muscular damage due to Leishmania (Leishmania) infantum chagasi infection remains to be fully established. The aim of this study was to describe the electromyographic and histological changes, as well as search for the presence of amastigote forms of Leishmania spp, CD3+ T-lymphocytes, macrophages and IgG in skeletal muscles of dogs with visceral leishmaniasis (VL). Four muscles (triceps brachial, extensor carpi radialis, biceps femoris and gastrocnemius) from a total of 17 naturally infected and six healthy dogs were used in this study. Electromyographic alterations such as fibrillation potentials, positive sharp waves and complex repetitive discharges were observed in, at least, three muscles from all infected dogs. Myocyte necrosis and degeneration were the most frequent muscular injury seen, followed by inflammatory reaction, fibrosis and variation in muscle fibers size. Immunohistochemistry in muscle samples revealed amastigote forms in 4/17 (23. 53%), IgG in 12/17 (70. 58%), CD3+ T-lymphocytes in 16/17 (94. 12%) and macrophages in 17/17 (100%) dogs. Statistically positive correlation was observed between: inflammatory infiltrate (p=0. 0305) and CD3+ immunoreaction (p=0. 0307) in relation to the number of amastigote forms; inflammatory infiltrate (p=0. 0101) and macrophage immunoreaction (p=0. 0127) in relation to the amount of CD3+; and inflammatory infiltrate (p=0. 0044) and degeneration/necrosis (p<0. 0001) in relation to the presence of macrophages. Our results suggest that different mechanisms contribute to the development of myocytotoxicity, including celular and humoral immune responses and direct muscular injury by the parasite. Nevertheless, the catabolic nature of the disease can probably interact with other factors, but cannot be incriminated as the only responsible for myositis.

Mechanisms Involved in the Beneficial Effects of Spironolactone after Myocardial Infarction

Introduction:Our objective was to analyze the effect of spironolactone on cardiac remodeling after experimental myocardial infarction (MI), assessed by matricellular proteins levels, cardiac collagen amount and distribution, myocardial tissue metalloproteinase inhibitor-1(TIMP-1) concentration, myocyte hypertrophy, left ventricular architecture, and in vitro and in vivo cardiac function.Methods:Wistar rats were assigned to 4 groups: control group, in which animals were submitted to simulated surgery (SHAM group; n=9); group that received spironolactone and in which animals were submitted to simulated surgery (SHAM-S group, n=9); myocardial infarction group, in which animals were submitted to coronary artery ligation (MI group, n=15); and myocardial infarction group with spironolactone supplementation (MI-S group, n=15). The rats were observed for 3 months.Results:The MI group had higher values of left cardiac chambers and mass index and lower relative wall thicknesses compared with the SHAM group. In addition, diastolic and systolic functions were worse in the MI groups. However, spironolactone did not influence any of these variables. The MI-S group had a lower myocardial hydroxyproline concentration and myocyte cross-sectional area compared with the MI group. Myocardial periostin and collagen type III were lower in the MI-S group compared with the MI-group. In addition, TIMP-1 concentration in myocardium was higher in the MI-S group compared with the MI group.Conclusions:The predominant consequence of spironolactone supplementation after MI is related to reductions in collagens, with discrete attenuation of other remodeling variables. Importantly, this effect may be modulated by periostin and TIMP-1 levels. © 2013 Minicucci et al.

Influência da obesidade sobre a composição de cadeias pesadas de Miosina e Fibrose intersticial miocárdica de ratos normotensos e espontaneamente hipertensos

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Influência da suplementação de vitamina D na dieta sobre remodelação cardíaca em ratos expostos à fumaça do cigarro

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Influência do diabetes mellitus no coração de ratos senescentes espontaneamente hipertensos

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