Metabolic Disturbances in Male Broilers of Different Strains. 1. Performance, Mortality, and Right Ventricular Hypertrophy

Two trials were carried out to test the susceptibility for metabolic disturbances of different strains of male broilers. In Trial 1, 1,890 male chickens were allotted in a randomized block design with seven treatments (Arbor Acres, Avian Farms, Cobb-500, Hubbard-Peterson, ISA, Naked Neck, and Ross) and six blocks of 45 chickens. Trial 2 involved 2,184 male chickens of six strains (Arbor Acres, Avian Farms, Cobb 500, Hubbard-Peterson, ISA Naked Neck, and Ross) allotted in seven complete blocks of 52 birds. The same management system was adopted for all birds, reared up to 42 d in an open house during late winter (Trial 1) or late autumn (Trial 2). The most marked differences observed among the strains tested was the lower BW and higher feed conversion of Naked Neck broilers. Total percentage mortalities were high among the most productive broilers, being more than 50% due to sudden death (SDS) and ascites syndrome (AS). No Naked Neck birds died as a consequence of these disturbances and the total mortalities were significantly lower (P ≤ 0.05) than the other strains. The ratio of right ventricle weight to total ventricle weight of the dead birds was over 0.25, except for Naked Neck birds, which presented a nonhypertrophic ratio. The two trials confirmed the relationship between high productivity and high incidence of SDS and AS and indicated that Naked Neck male broilers are resistant to these metabolic disturbances.

Left ventricular sphericity index predicts systolic dysfunction in rats with experimental aortic regurgitation

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

Myocardial contractile dysfunction contributes to the development of heart failure in rats with aortic stenosis

Objectives: To analyze the potential contribution of contractility state and ventricular geometry to the development of heart failure in rats with aortic stenosis.Methods: Rats were divided into three groups: compensated aortic stenosis (AS, n = 11), heart failure AS (n = 12) and control rats (C, n = 13).Results: After 21 weeks, failing AS rats presented higher systolic (C = 36.6 +/- 3.1, AS-78.6 +/- 4.8*, failing AS = 104.6 +/- 7.8*) and diastolic meridian stress (C = 6.9 +/- 0.4, AS = 20.1 +/- 1.1*, failing AS = 43.2 +/- 3.2*(dagger)), hydroxyproline (C = 3.6 +/- 0.7 mg/g, AS = 6.6 +/- 0.6* mg/g, failing AS = 9.2 +/- 1.4*(dagger) mg/g) and cross-sectional area (C = 338 +/- 25 mu m(2), AS = 451 +/- 32* mu m(2), failing AS = 508 +/- 36*(dagger) mu m(2)), in comparison with control and compensated AS animals (*p < 0.05 vs. control, (dagger)p < 0.05 vs. AS). In the isometric contraction study, considering the time from peak tension to 50% relaxation (RT50), the relative variation responses, following post-rest contraction and increase in Ca2+ concentration, were higher in failing AS than compensated AS animals. In contrast, following post-rest contraction, compensated AS group presented higher values of the peak developed tension (DT) than failing AS group. Following beta-adrenergic stimulation, control animals presented higher values of +dT/dt and -dT/dt than AS animals. In addition, failing AS animals presented higher TPT values than compensated AS animals.Conclusion: Myocardial contractile dysfunction contributes to the development of heart failure in rats with aortic stenosis. (c) 2006 Elsevier B.V.. All rights reserved.

Myocardial remodeling and dysfunction are induced by chronic food restriction in spontaneously hypertensive rats

Several studies have shown alterations in hearts from animals subjected to food restriction (FR). However, few experiments in hearts evaluating pressure overload have been reported. We examined the effects of chronic FR on myocardial function and morphology in spontaneously hypertensive rats (SHR). Sixty-day-old SHR were fed a control (C) or a restricted diet (daily intake reduced to 50% of amount of food consumed by the control group) for 90 days. Myocardial performance was studied in isolated left ventricular (LV) papillary muscle. Food restriction decreased body weight and LV weight; LV weight/body-weight ratio was lower in the food-restricted group (SHR-C, 2.84 +/- 0.21 mg/g; SHR-FR, 2.56 +/- 0.24 mg/g; P <.05). Food restriction did not change arterial systolic blood pressure. Myocyte surface area was lower in the food-restricted group (P <.01). Food restriction induced myocardial ultrastructural alterations including reduced sarcoplasm content, reduced and disorganized myofilaments, disorganized Z line, dilated sarcoplasmic reticulum, and deep infoldings of plasma membrane. Myocardial hydroxyproline concentration was increased in the restricted rats. Peak developed tension (P <.05) and maximum rate of tension development (P <.01) were decreased in the SHR-FR group. In conclusion, myocardium of SHR subjected to chronic FR presents attenuation of hypertrophy development, ultrastructural changes, increased collagen content, and systolic dysfunction. (c) 2006 Elsevier B.V. All rights reserved.

Myocardial fibrosis rather than hypertrophy induces diastolic dysfunction in renovascular hypertensive rats

The aim of the present study was to evaluate the-effect of interstitial fibrosis alone or associated with hypertrophy. on diastolic myocardial function in renovascular hypertensive rats. Myocardial function was evaluated in isolated papillary muscle from renovascular hypertensive Wistar rats (RHT, n = 14), renovascular hypertensive rats treated with the angiotensin converting enzyme inhibitor (ACEI) ramipril, 20 mg.kg(-1).day(-1) (RHT RAM, n = 14), and age-matched unoperated and untreated Wistar rats (CONT, n = 12). The ACEI treatment for 3 weeks allowed the regression of myocyte mass and the maintenance of interstitial fibrosis. Myocardial passive stiffness was analyzed by the resting tension - length relationship. The myocardial fibrosis was evaluated by measuring myocardial hydroxyproline (Hyp) concentration and by histological studies of the myocardium stained with hematoxylin and eosin or picrosirius red. Left ventricular weight was significantly higher in RHT (0.97 +/- 0.12 g) compared with CONT (0.66 +/- 0.06 g) and RHT RAM (0.69 +/- 0.14 g). The Hyp levels were 2.9 +/- 0.4, 3.4 +/- 0.3, and 3.8 +/- 0.4 mu g/mg of dry tissue for the CONT, RHT, and RHT RAM, respectively. Perivascular and interstitial fibrosis were observed in RHT and RHT RAM groups. There were lymphomononuclear inflammatory exudate and edema around arteries, involving adjacent myocytes in the RHT group. There was an increased passive stiffness in RHT and RHT RAM groups compared with the CONT group. In conclusion, our results indicate that the Impaired diastolic function in the renovascular hypertensive rats is related to interstitial fibrosis rather than to myocardial hypertrophy.

A exposição à fumaça de cigarro intensifica a remodelação ventricular após o infarto agudo do miocárdio

OBJETIVO: Analisar os efeitos da exposição à fumaça de cigarro (EFC) na remodelação ventricular após o infarto agudo do miocárdio (IAM). MÉTODOS: Ratos foram infartados e distribuídos em dois grupos: C (controle, n = 31) e F (EFC: 40 cigarros/dia, n = 22). Após seis meses, foi realizado ecocardiograma, estudo funcional com coração isolado e morfometria. Para comparação, foi utilizado o teste t (com média ± desvio padrão) ou teste de Mann-Whitney (com mediana e percentis 25 e 75). RESULTADOS: Os animais EFC apresentaram tendência a maiores áreas ventriculares diastólicas (C = 1,5 ± 0,4 mm², F = 1,9 ± 0,4 mm²; p = 0,08) e sistólicas (C = 1,05 ± 0,3 mm², F = 1,32 ± 0,4 mm²; p = 0,08) do VE. A função sistólica do VE, avaliada pela fração de variação de área, tendeu a ser menor nos animais EFC (C = 31,9 ± 9,3 %, F = 25,5 ± 7,6 %; p = 0,08). Os valores da - dp/dt dos animais EFC foram estatisticamente inferiores (C = 1474 ± 397 mmHg, F = 916 ± 261 mmHg; p = 0,02) aos animais-controle. Os animais EFC apresentaram maior peso do VD, ajustado ao peso corporal (C = 0,8 ± 0,3 mg/g, F = 1,3 ± 0,4 mg/g; p = 0,01), maior teor de água nos pulmões (C = 4,8 (4,3-4,8)%, F = 5,4 (5,1-5,5); p = 0,03) e maior área seccional do miócito do VE (C = 239,8 ± 5,8 µm², F = 253,9 ± 7,9 µm²; p = 0,01). CONCLUSÃO: A exposição à fumaça de cigarro intensifica a remodelação ventricular após IAM.

Food restriction promotes downregulation of myocardial L-type Ca2+ channels

Food restriction (FR) has been shown to impair myocardial performance. However, the mechanisms behind these changes in myocardial function due to FR remain unknown. Since myocardial L-type Ca2+ channels may contribute to the cardiac dysfunction, we examined the influence of FR on L-type Ca2+ channels. Male 60-day-old Wistar rats were fed a control or a restricted diet (daily intake reduced to 50% of the amount of food consumed by the control group) for 90 days. Myocardial performance was evaluated in isolated left ventricular papillary muscles. The function of myocardial L-type Ca2+ channels was determined by using a pharmacological Ca2+ channel blocker, and changes in the number of channels were evaluated by mRNA and protein expression. FR decreased final body weights, as well as weights of the left and right ventricles. The Ca2+ channel blocker diltiazem promoted a higher blockade on developed tension in FR groups than in controls. The protein content of L-type Ca2+ channels was significantly diminished in FR rats, whereas the mRNA expression was similar between groups. These results suggest that the myocardial dysfunction observed in previous studies with FR animals could be caused by downregulation of L-type Ca2+ channels.

Early echocardiographic predictors of increased left ventricular end-diastolic pressure three months after myocardial infarction in rats

Background: The objective of this study was to determine the early echocardiographic predictors of elevated left ventricular end-diastolic pressure (LVEDP) after a long follow-up period in the infarcted rat model.Material/Methods: Five days and three months after surgery, sham and infarcted animals were subjected to transthoracic echocardiography. Regression analysis and receiver-operating characteristic (ROC) curve were performed for predicting increased LVEDP 3 months after MI.Results: Among all of the variables, assessed 5 days after myocardial infarction, infarct size (OR: 0.760; CI 95% 0.563-0.900; p=0.005), end-systolic area (ESA) (OR: 0.761; Cl 95% 0.564-0.900; p=0.008), fractional area change (FAC) (OR: 0.771; CI 95% 0.574-0.907; p=0.003), and posterior wall-shortening velocity (PWSV) (OR: 0.703; CI 95% 0.502-0.860; p=0.048) were predictors of increased LVEDP. The LVEDP was 3.6 +/- 1.8 mmHg in the control group and 9.4 +/- 7.8 mmHg among the infarcted animals (p=0.007). Considering the critical value of predictor variables in inducing cardiac dysfunction, the cut-off value was 35% for infarct size, 0.33 cm(2) for ESA, 40% for FAC, and 26 mm/s for PWSV.Conclusions: Infarct size, FAC, ESA, and PWSV, assessed five days after myocardial infarction, can be used to estimate an increased LVEDP three months following the coronary occlusion.

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 sm oke in rats.

Combined exercise training in asymptomatic elderly with controlled hypertension: Effects on functional capacity and cardiac diastolic function

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Myocardial dysfunction induced by food restriction is related to morphological damage in normotensive middle-aged rats

Previous works from our laboratory have revealed that food restriction (FR) promotes discrete myocardial dysfunction in young rats. We examined the effects of FR on cardiac function, in vivo and in vitro, and ultrastructural changes in the heart of middle-aged rats. Twelve-month-old Wistar- Kyoto rats were fed a control (C) or restricted diet (daily intake reduced to 50% of the control group) for 90 days. Cardiac performance was studied by echocardiogram and in isolated left ventricular (LV) papillary muscle by isometric contraction in basal condition, after calcium chloride (5.2 mM) and beta- adrenergic stimulation with isoproterenol (10(-6) M). FR did not change left ventricular function, but increased time to peak tension, and decreased maximum rate of papillary muscle tension development. Inotropic maneuvers promoted similar effects in both groups. Ultrastructural alterations were seen in most FR rat muscle fibers and included, absence and/or disorganization of myofilaments and Z line, hyper-contracted myofibrils, polymorphic and swollen mitochondria with disorganized cristae, and a great quantity of collagen fibrils. In conclusion, cardiac muscle sensitivity to isoproterenol and elevation of extracellular calcium concentration is preserved in middle-aged FR rats. The intrinsic muscle performance depression might be related to morphological damage.

Severe food restriction induces myocardial dysfunction related to SERCA2 activity

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

Tissue Vitamin A Insufficiency Results in Adverse Ventricular Remodeling after Experimental Myocardial Infarction

Background/Aims: The role of tissue vitamin-A insufficiency on post-infarction ventricular remodeling is unknown. We tested the hypothesis that cardiac vitamin A insufficiency on post-infarction is associated with adverse myocardial remodeling. Methods: After infarction, rats were allocated into two groups: C (controls, n=25); VA (dietary vitamin A restriction, n= 26). After 3 months, the animals were submitted to echocardiogram, morphometric and biochemical analysis. Results: Rats fed the vitamin-A-deficient diet had lower heart and liver retinol concentration and normal plasma retinol. There were no differences in infarct size between the groups. VA showed higher diastolic left ventricular area normalised by body weight (C= 1.81 +/- 0.4 cm2/kg, VA= 2.15 +/- 0.3 cm2/kg; p=0.03), left ventricular diameter (C= 9.4 +/- 1.4 mm, VA= 10.5 +/- 1.2 mm; p=0.04), but similar systolic ventricular fractional area change (C= 33.0 +/- 10.0 %, VA= 32.1 +/- 8.7 %; p=0.82). VA showed decreased isovolumetric relaxation time normalised by heart rate (C= 68.8 +/- 11.4 ms, VA= 56.3 +/- 16.8 ms; p=0.04). VA showed higher interstitial collagen fraction (C= 2.8 +/- 0.9 %, VA= 3.7 +/- 1.1 %; p=0.05). There were no differences in myosin heavy chain expression, metalloproteinase 2 and 9 activation, or IFN-gamma and TNF-alpha cardiac levels. Conclusion: Local tissue vitamin A insufficiency intensified ventricular remodeling after MI, worsening diastolic dysfunction. Copyright (C) 2010 S. Karger AG, Basel

Myostatin and follistatin expression in skeletal muscles of rats with chronic heart failure

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