Effect of gestational protein restriction on left ventricle hypertrophy and heart angiotensin II signaling pathway in adult offspring rats

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

Activation of calcineurin in human failing heart ventricle by endothelin-1, angiotensin II and urotensin II

1 The calcineurin (CaN) enzyme-transcriptional pathway is critically involved in hypertrophy of heart muscle in some animal models. Currently there is no information concerning the regulation of CaN activation by endogenous agonists in human heart. 2 Human right ventricular trabeculae from explanted human ( 14 male/2 female) failing hearts were set up in a tissue bath and electrically paced at 1Hz and incubated with or without 100 nM endothelin-1 (ET-1), 10 mu M, angiotensin-II (Ang II) or 20 nM human urotensin-II (hUII) for 30 min. Tissues from four patients were incubated with 200 nM tacrolimus (FK506) for 30 min and then incubated in the presence or absence of ET-1 for a further 30 min. 3 ET-1 increased contractile force in all 13 patients (P < 0.001). Ang II and hUII increased contractile force in three out of eight and four out of 10 patients but overall nonsignificantly (P > 0.1). FK506 had no effect on contractile force (P = 0.12). 4 ET-1, Ang II and hUII increased calcineurin activity by 32, 71 and 15%, respectively, while FK506 reduced activity by 34%. ET-1 in the presence of FK506 did not restore calcineurin activity (P = 0.1). 5 There was no relationship between basal CaN activity and expression levels in the right ventricle. Increased levels of free phosphate were detected in ventricular homogenates that were incubated with PKC epsilon compared to samples incubated without PKCe. 6 Endogenous cardiostimulants which activate G alpha q-coupled receptors increase the activity of calcineurin in human heart following acute (30 min) exposure. PKC may contribute to this effect by increasing levels of phosphorylated calcineurin substrate.

Myoarchitecture and vasculature of the heart ventricle in some freshwater teleosts

The morphological characteristics of the ventricular myocardium and of coronary vascularization were studied in three freshwater teleost species, Piaractus mesopotamicus, Colossoma macropomum and Clarias gariepinus (African catfish), by correlating their ventricular shapes and swimming habits. In Piaractus mesopotamicus and Colossoma macropomum, species with highly active swimming habits, the cardiac ventricle showed a pyramidal shape and a richly vascularized myocardium consisting of an outer compact layer and inner spongy layer. In Clarias gariepinus, a less active species, we observed a saccular ventricle with a mixed myocardium and coronary arteries, in contrast to the ventricular structure of other species described in the literature.

Morphological studies on the heart ventricle of African catfish (Clarias gariepinus)

The histological and ultrastructural characteristics of the heart ventricle in Clarias gariepinus (African catfish) has been studied by light microscopy and transmission electron microscopy. The ventricle of the heart has a saccular shape and the myocardial wall consists of an outer thin compact myocardium and an inner well-developed spongy myocardium. The myocardial layer has small myocytes, interstitial spaces and blood vessels. The myocytes are the major constituents of the ventricular wall. They are long cells, with large nuclei, and predominantly euchromatin. The sarcoplasmic reticulum of the ventricular myocytes consists of a network of tubules and subsarcolemmal cisternae oriented mainly along the longitudinal axis of the myofibrils. In contrast to the ventricular structure of other fish species described in the literature (Greer-Walker et al., 1985 Santer, 1985 Sanchez-Quintana et al., 1995, 1996), the African catfish, a freshwater sedentary fish recently introduced in neotropical climatic environments, showed a saccular ventricle that consisted of two muscle layers, a thin compact layer with large vessels and a developed spongy layer. The ultrastructure of the ventricular myocardium of C.gariepinus is similar to that of other teleosts, inclusive that of fish with other swimming habits.

Disproportionate pregnancy-induced myocardial hypertrophy in women with essential hypertension

BACKGROUND Pregnancy and arterial hypertension (AH) have a prohypertrophic effect on the heart. It is suspected that the 2 conditions combined cause disproportionate myocardial hypertrophy. We sought to evaluate myocardial hypertrophy (LVH) and left ventricular function in normotensive and hypertensive women in the presence or absence of pregnancy.METHODS This prospective cross-sectional study included 193 women divided into 4 groups: hypertensive pregnant (HTP; n = 57), normotensive pregnant (NTP; n = 47), hypertensive nonpregnant (HTNP; n = 41), and normotensive nonpregnant (NTNP; n = 48). After clinical and echocardiographic evaluation, the variables were analyzed using 2-way analysis of variance with pregnancy and hypertension as factors. Left ventricular mass (LVM) was compared using nonparametric analysis of variance and Dunn′s test. Predictors of LVH and diastolic dysfunction were analyzed using logistic regression (significance level, P < 0.05).RESULTS Myocardial hypertrophy was independently associated with hypertension (odds ratio (OR) = 11.1, 95% confidence interval (CI) = 3.2-38.5; P < 0.001) and pregnancy (OR = 6.1, 95% CI = 2.6-14.3; P < 0.001) in a model adjusted for age and body mass index. Nonpregnant women were at greater risk of LVH in the presence of AH (OR = 25.3, 95% CI = 3.15-203.5; P = 0.002). The risk was additionally increased in hypertensive women during pregnancy (OR = 4.3, 95% CI = 1.7-10.9; P = 0.002) in the model adjusted for stroke volume and antihypertensive medication. Although none of the NTNP women presented with diastolic dysfunction, it was observed in 2% of the NTP women, 29% of the HTNP women, and 42% of the HTP women (P < 0.05).CONCLUSIONS Hypertension and pregnancy have a synergistic effect on ventricular remodeling, which elevates a woman's risk of myocardial hypertrophy. © 2013 © American Journal of Hypertension, Ltd 2013. All rights reserved.

Infarto do miocárdio experimental em ratos: Análise do modelo

One of the most often used strategies to study the physiopathological alterations caused by coronary occlusion is the use of the experimental infarction model in rats. Among other factors, this is due to the similarities in the physiopathological alterations that occur after the infarction in humans. One must consider, however, that this model has characteristics that can hinder the use as well as the interpretation of eventual outcomes. Thus, this review aims at analyzing the main characteristics of the experimental infarction model in rats, discussing the coronary occlusion technique, the consequences and the methods of morphological and functional assessment of the infarction and its clinical implications.

Hypertrophied myocardium is more dependent on extracellular calcium than the normal cardiac muscle

Background: The aim of this study was to analyze stable hypertrophied myocardial function and its response to inotropic maneuvers in rats submitted to renovascular hypertension for a 10-week period (RHT group, n=10). Material/Methods: Myocardial performance was studied in isolated left ventricle papillary muscles in isometric contraction under the following conditions: at postrest contraction of 30 seconds (PRC), at extracellular calcium (ECa 2+) chloride concentration of 1.25 and 5.20 mM, and after beta-adrenergic stimulation with 10 -6 M isoproterenol (ISOP). Results: The results were compared with normotensive Wistar controls rats (C group, n=10). In basal condition, resting tension, and contraction time (TPT) were greater, while relaxation time (RT 50) tended to be longer in RHT than C group. PRC and ISOP promoted a similar change in muscle function response intensity (Δ) in both groups. ECa 2+ shift did not change TPT in the C group and decreased TPT in the RHT animals; Δ was different between these groups. RT 50 increased in C and decreased in RHT, both without statistical significance; however, Δ was different. Conclusions: These results suggest that hypertrophied myocardial dysfunction may be attibuted to changes in intracellular calcium cycling. © Med Sci Monit, 2010.

Relevãncia do padrão de remodelamento ventricular no modelo de infarto do miocárdio em ratos

Background: The relevance of the remodeling pattern in the model of infarcted rats is not known. Objective: To analyze the presence of different patterns of remodeling in this model and its functional implications. Methods: Infarcted rats (n=47) have been divided according to the geometry pattern, analyzed by echocardiogram: normal (normal mass index and normal relative thickness), concentric remodeling (normal mass index and increased relative thickness), concentric hypertrophy (increased mass index and increased relative thickness) and eccentric hypertrophy (increased mass index and normal relative thickness). Data are median and interquartile range. Results: Infarcted rats showed only two of the four geometric patterns: normal pattern (15%) and eccentric hypertrophy - EH (85%). Groups of normal pattern and EH showed no differences in the values of fractional area change (Normal = 32.1-28.8 to 50.7; EH = 31.3-26.5 to 36.7; p = 0.343). Out of the infarcted animals, 34 (74%) had systolic dysfunction, detected by fractional area change. Considering these two geometry patterns, 77% of animals with eccentric hypertrophy and 57% with normal geometry presented systolic dysfunction (p=0.355). The relative wall thickness, the geometric patterns and the body mass index were not predictors of ventricular dysfunction (p>0.05). On the other hand, infarct size was a predictive factor for ventricular dysfunction in univariate analysis (p<0.001) and multivariate analysis (p = 0.004). Conclusion: Rats that underwent coronary occlusion showed two different patterns of remodeling, which do not constitute a predictor of ventricular dysfunction.

Could albumin level explain the higher mortality in hemodialysis patients with pulmonary hypertension?

Background: The pathogenesis of pulmonary hypertension (PH) in hemodialysis is still unclear. The aim of thisstudy was to identify the risk factors associated with the presence of PH in chronic hemodialysis patients and toverify whether these factors might explain the highest mortality among them.Methods: We conducted a retrospective study of hemodialysis patients who started treatment from August 2001to October 2007 and were followed up until April 2011 in a Brazilian referral medical school. According to theresults of echocardiography examination, patients were allocated in two groups: those with PH and those withoutPH. Clinical parameters, site and type of vascular access, bioimpedance, and laboratorial findings were comparedbetween the groups and a logistic regression model was elaborated. Actuarial survival curves were constructed andhazard risk to death was evaluated by Cox regression analysis.Results: PH > 35 mmHg was found in 23 (30.6%) of the 75 patients studied. The groups differed in extracellularwater, ventricular thickness, left atrium diameter, and ventricular filling. In a univariate analysis, extracellular waterwas associated with PH (relative risk = 1.194; 95% CI of 1.006 1.416; p = 0.042); nevertheless, in a multiple model,only left atrium enlargement was independently associated with PH (relative risk =1.172; 95% CI of 1.010 1.359;p = 0.036). PH (hazard risk = 3.008; 95% CI of 1.285 7.043; p = 0.011) and age (hazard risk of 1.034 per year of age;95% CI of 1.000 7.068; p = 0.047) were significantly associated with mortality in a multiple Cox regression analysis.However, when albumin was taken in account the only statistically significant association was between albuminlevel and mortality (hazard risk = 0.342 per g/dL; 95% CI of 0.119 0.984; p = 0.047) while the presence of PH lost itsstatistical significance (p = 0.184). Mortality was higher in patients with PH (47.8% vs 25%) who also had astatistically worse survival after the sixth year of follow up.Conclusions: PH in hemodialysis patients is associated with parameters of volume overload that sheds light on itspathophysiology. Mortality is higher in hemodialysis patients with PH and the low albumin level can explain thisassociation.© 2012 Greenfield et al.; licensee BioMed Central Ltd.

Cardiac remodeling induced by smoking: Concepts, relevance, and potential mechanisms

Cardiac or ventricular remodeling is characterized by molecular, cellular, and interstitial alterations that lead to changes in heart size, mass, geometry and function in response to a given insult. Currently, tobacco smoke exposure is recognized as one of these insults. Indeed, tobacco smoke exposure induces the enlargement of the left-sided cardiac chambers, myocardial hypertrophy, and ventricular dysfunction. Potential mechanisms for these alterations include hemodynamic and neurohormonal changes, oxidative stress, inflammation, nitric oxide bioavailability, matrix metalloproteinases and mitogen-activated protein kinase activation. This review will focus on the concepts, relevance, and potential mechanisms of cardiac remodeling induced by tobacco smoke. © 2012 Bentham Science Publishers.

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.

Improved systolic ventricular function with normal myocardial mechanics in compensated cardiac hypertrophy

There still controversy about the relation between changes in myocardial contractile function and global left ventricular (LV) performance during stable concentric hypertrophy. To clarify this, we analyzed LV function in vivo and myocardial mechanics in vitro in rats with pressure overload-induced cardiac hypertrophy. Male Wistar rats (70 g) underwent ascending aorta stenosis for 8 weeks (group AAS, n=9). LV performance was assessed by transthoracic echocardiography under light anesthesia. Myocardial function was studied in isolated papillary muscle preparation during isometric contraction. The data were compared with age- and sex-matched sham-operated rats (group C, n=9). LV weight-to-body weight ratio (C: 2.0 ± 0.5 mg/g; AAS: 3.3 ± 0.7 mg/g), LV relative wall thickness (C: 0.19 ± 0.02; AAS; 0.34 ± 0.10), and LV fractional shortening (C: 54 ± 5%; AAS: 70 ± 8%) were increased in the group AAS (p<0.05). Echocardiographic analysis also indicated a significant association (r=0.74; p<0.001) between percent fractional shortening and LV relative wall thickness. The performance of AAS isolated muscle revealed that active tension (C: 6.6 ± 1.7 g/mm 2; AAS: 6.5 ± 1.5 g/mm 2) and maximum rate of tension development (C: 69 ± 21 g/mm 2/s; AAS: 69 ± 18 g/mm 2) were not significantly different from group C (p>0.05). In conclusion: 1) Compensated pressure-overload myocardial hypertrophy is associated with preserved myocardial function and increased ventricular performance; 2) The improved LV function might be due to the ventricular remodeling characterized by an increased relative wall thickness. Copyright © 2002 By PJD Publications Limited.

Heart failure-induced skeletal myopathy in spontaneously hypertensive rats

Background: Although skeletal muscle atrophy and changes in myosin heavy chain (MyHC) isoforms have often been observed during heart failure, their pathophysiological mechanisms are not completely defined. In this study we tested the hypothesis that skeletal muscle phenotype changes are related to myogenic regulatory factors and myostatin/follistatin expression in spontaneously hypertensive rats (SHR) with heart failure. Methods: After developing tachypnea, SHR were subjected to transthoracic echocardiogram. Pathological evidence of heart failure was assessed during euthanasia. Age-matched Wistar-Kyoto (WKY) rats were used as controls. Soleus muscle morphometry was analyzed in histological sections, and MyHC isoforms evaluated by electrophoresis. Protein levels were assessed by Western blotting. Statistical analysis: Student's t test and Pearson correlation. Results: All SHR presented right ventricular hypertrophy and seven had pleuropericardial effusion. Echocardiographic evaluation showed dilation in the left chambers and left ventricular hypertrophy with systolic and diastolic dysfunction in SHR. Soleus weight and fiber cross sectional areas were lower (WKY 3615±412; SHR 2035±224 μm2; P < 0.001), and collagen fractional volume was higher in SHR. The relative amount of type I MyHC isoform was increased in SHR. Myogenin, myostatin, and follistatin expression was lower and MRF4 levels higher in SHR. Myogenin and follistatin expression positively correlated with fiber cross sectional areas and MRF4 levels positively correlated with I MyHC isoform. Conclusion: Reduced myogenin and follistatin expression seems to participate in muscle atrophy while increased MRF4 protein levels can modulate myosin heavy chain isoform shift in skeletal muscle of spontaneously hypertensive rats with heart failure. © 2012 Elsevier B.V.