A rat coronary artery ligation leads to a wide range of infarct size, cardiac remodeling and left ventricular dysfunction. In addition, it is accepted that the coronary occlusion consequences are closely related to infarction size, which is a powerful determinant of survival , ventricularremodeling , and cardiac systolic function . In order to determine the association between infarct size and outcomes after coronary occlusion, the animals were divided into three groups (small, moderate or large infarct size), but this division was not homogeneous among the studies because the animals were randomly placed in the groups. Consequently, the infarct size that is necessary to determine morphological, functional, and clinical alterations after the coronary occlusion, still needs to be determined. The present study was carried out to determine the critical infarct size to induce ventricularremodeling, cardiac dysfunction, and heart failure in a rat model.
In spite of the conceptual importance of this stress, we are not aware of previous studies that have evaluated this variable through echocardiography as a determinant of remodeling in this model. In our study, wall stress, measured noninvasively in the early phase of infarction, was an independent predictor of ventricularremodeling three months after coronary occlusion. Therefore, we believe that our study adds important data to the association of wall stress with left ventricular dilatation, suggesting that this variable could be used as a marker of the remodeling process.
Background/Aims: The role of tissue vitamin-A insufficiency on post-infarction ventricularremodeling 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
In the vascular endothelium, it is well established that cigarette smoke induces ROS production via NADPH oxidase activation [7-9]. Previous studies also suggest that tobacco smoke may induce ventricularremodeling via changes in oxidative stress [18, 19]. However, the role that NADPH oxidase plays in cardiac remodeling that is induced by smoking is unknown. Fig. 1. The cardiac NADPH oxidase activity, which was increased in the EST group compared to the controls. Table 3. Total protein, lipid hydroperoxide concentration and antioxidant enzyme activity in the cardiac tissue. C: control animals; ETS: animals exposed to tobacco smoke; LH: lipid hydroperoxide; CAT: catalase; GSH-Px: glutathione peroxidase; SOD: superoxide dismutase; TP: total protein. The data are expressed as the mean ± SD or the median (including the lower quartile and upper quartile).
O remodelamento cardíaco é uma das consequências da insuficiência cardíaca (IC) e a terapia de ressincronização cardíaca (TRC) uma das opções terapêuticas que pode auxiliar no remodelamento ventricular reverso. O objetivo do estudo é analisar o papel da TRC no remodelamento ventricular reverso em pacientes com IC. Estudo de coorte retrospectivo, censo, realizado no ambulatório de miocardiopatias do Instituto de Cardiologia de Santa Catarina (ICSC), em pacientes portadores de IC que foram submetidos à TRC no período de 2001 a 2013. A coleta de dados foi realizada por meio de prontuários e os dados analisados sob a forma descritiva e bivariada através dos testes T pareado e qui- quadrado, com nível de significância de p< 0,05. Estudo aprovado pelo CEP da Unisul. Os resultados revelaram-se com predomínio do sexo masculino (57,1%), faixa etária ≥ 50 anos (81,0%), ritmo sinusal (73,8%) e etiologia não-isquêmica (76,25%). Pré-TRC 78,6% apresentaram classe funcional (NYHA) III e IV, e pós-TRC totalizaram 4,7%. Houve aumento da fração de ejeção (p< 0.01) e queda discreta dos volumes do ventrículo esquerdo. A regurgitação mitral moderada e importante pré-TRC totalizou o valor de 49,9% e pós-TRC a regurgitação discreta teve predomínio (57,1%). Uso de drogas que inibem o sistema renina-angiotensina-aldosterona totalizou 92,8% pré e pós TRC. O Carvedilol apresentou tendência a menor uso pós-TRC. O uso de qualquer betabloqueador antes ou após a TRC (88,1% pré-TRC e 64,3% pós-TRC) revelou-se significativa (p<0,01). A TRC possibilitou, portanto, alterações favoráveis na fração de ejeção, nos volumes do ventrículo esquerdo e na regurgitação mitral, além de melhora clínica dos pacientes.
ABSTRACT: This paper describes a case of congenital aortic stenosis with eccentric left ventricular hypertrophy associated with hypothyroidism in a 1-year-old Bourdeaux Mastiff dog. The dog had ascites, apathy, alopecic and erythematous skin lesions in different parts of the body. A two-dimensional echocardiogram revealed aortic valve stenosis, with poststenotic dilation in the ascending aorta. The same exam showed eccentric hypertrophy and dilation of the left ventricle during systole and diastole. Aortic stenosis usually results in concentric left ventricular hypertrophy instead of eccentric hypertrophy; and therefore, this finding was very unusual. Hypothyroidism, which is uncommon in young dogs, may be incriminated as the cause of ventricular dilation, making this report even more interesting. Because hypothyroidism would only result in dilatation, the eccentric hypertrophy was attributed to pressure overload caused by aortic stenosis. Thus, cardiac alterations of this case represent a paradoxical association of both diseases.
Methodology/Principal Findings: RV remodeling was induced in rats by intraperitoneal injection of monocrotaline (MCT). RV systolic pressure (RVSP) was measured at the end of each week after MCT injection. Blood samples were drawn for brain natriuretic peptide (BNP) ELISA analysis. The hearts were excised for histopathological, ultrastructural, immunohistochem- ical, and Western blotting analyses. The MCT-injected rats exhibited greater mortality and less weight gain and showed significantly increased RVSP and RV hypertrophy during the second week. These worsened during the third week. MCT injection for three weeks caused pathological RV remodeling, characterized by hypertrophy, fibrosis, dysfunction, and RV mitochondrial impairment, as indicated by increased levels of apoptosis. Nicorandil improved survival, weight gain, and RV function, ameliorated RV pressure overload, and prevented maladaptive RV remodeling in PAH rats. Nicorandil also reduced the number of apoptotic cardiomyocytes, with a concomitant increase in Bcl-2/Bax ratio. 5-hydroxydecanoate (5-HD) reversed these beneficial effects of nicorandil in MCT-injected rats.
The estimation of cardiac hypertrophy, by ventricular weight and body weight ratio is used in several experimental models. After coronary occlusion, an inflammatory process sets in on the infarction region, and afterwards a fibrous scar replaces this region. In the right ventricle and in the regions without infarction of the left ventricle, myocyte growth and collagen clumping occur. So the increase in ventricular mass does not reflect exclusively the hypertrophy process. Des- pite these limitations, the VM/BM rate is accepted in the literature as a parameter of cell growth in this model 13-16 . In
influence of LV dysfunction on CCL21 levels, the high levels in AS patients as compared with our previous data on CCL21 levels in post-MI HF , suggest that the raised levels of CCL21 in AS patients do not merely reflect accompanying HF. There was a significant association between CCL21 and backscatter as a marker of aortic valve calcification, and in particular with decreased aortic valve area. In fact, CCL21 was significantly associated with aortic valve area and backscatter also after correction for several confounders. Moreover, in the experimental model of pressure overload following AB, myocardial CCL21 mRNA expression was significantly increased in both compensat- ed and decompensated hypertrophy, and CCL21 protein levels were significantly increased in hearts with overt HF. These findings suggest that CCL21 might have a role in the remodeling process secondary to pressure overload and not merely reflect associated conditions in these patients.
To further elucidate the structural remodeling and thereby the qualitative characteristics of the healing wound we assessed the collagen content of the myocardial scar 3 weeks post MI. The larger infarcted myocardial tissue area was characterized by increased collagen content in the infarcted myocardium of animals with depleted circulating NOS3. The time point “3 weeks post MI” is frequently regarded as the “stable” phase in the remodeling process termed “scar maturation phase” . It is critical that a strong, mature scar is formed as early as possible since the structurally weakened infarct area is subject to expansion during the proliferative phase and vulnerable to rupture . Preservation of the extracellular matrix and collagen de- position at the site of myocyte necrosis are essential for structural stability of the infarcted heart. Excessive collagen degradation and impaired fibrous tissue formation may reduce the tensile strength of the necrotic zone and lead to enhanced infarct expansion [31, 32]. On the other hand, increased fibrosis stiffens the left ventricle and impairs its diastolic filling .
Sixty dogs with idiopathic dilated cardiomyopathy were randomly treated with traditional therapy – digitalis, diuretics, angiotensin-converting inhibitors – (group A) or treated with these drugs plus carvedilol (group B). Echocardiographic variables were measured before and after 3, 13, 26, and 52 weeks of treatment or until death. Comparisons between groups and time were performed. No significant differences between groups were found in the most of the echocardiographic variables. The left ventricular end-systolic diameter indexed to body surface area (LVESDi) increased significantly in the group A dogs compared to the group B animals. The survival of groups A and B dogs were not different (P-value=0.1137). In conclusion, the stability of the LVESDi observed in the group treated with carvedilol may represent the beneficial effect over the ventricularremodeling.
Moreover, recent autopsy studies demonstrated significant cardiac hypertrophy, coronary microvascular rarefaction and myocardial fibrosis in patients with HFpEF compared to con- trols. We further extend these previous results by adding information on LV myocardial structure obtained by myocardial biopsy. We found a strong inverse correlation between the extent of the left ventricular extracellular matrix and the invasively measured stroke volume. In fact, structural changes in both heart chambers seem to independently predict outcome: left ventricularremodeling processes with stiffening, filling impairment and consecutive rise in left ventricular filling pressures on one hand and right ventricular systolic dysfunction due to an increased afterload with variable degrees of pulmonary vascular remodeling on the other hand are major determinants of the clinical course . Thus, estimates of sPAP by transthoracic echocardiography together with a visual assessment of the RV may be appropriate to predict prognosis in HFpEF patients. Interestingly, we did not observe a significant correlation between LV filling pressures or LV mass and myocardial fibrosis obtained by myocardial biopsy. This may suggest that myocardial fibrosis although a significant driving force in the development of HFpEF might not be the sole trigger for an increase in LV filling pressures in the pathogenesis of HFpEF. Recent data by Zile et al. suggests that myocardial stiffness in patients with HFpEF not only depends on the extent of extracellular matrix, but also on myo- cardial titin homeostasis, which might explain our findings . However, our results need to be interpreted with caution since our number of LV biopsies is rather small and our histol- ogy-based analysis should be more considered as hypothesis-generating and foster future investigations.
Contrarily to our original hypothesis, the supplementation of beta-carotene did not modify the variables that evaluated the lipoperoxidation. In fact, the relation GSH/GSSG, and the levels of GSH, GSSG and lipoperoxides of the group supplemented with beta-carotene were not different from the infarcted animals without supplementation. It should be considered that the concentrations of GSH and GSSG and their association indicate how much of the GSH was used to preserve the antioxidant/oxidant equilibrium. So, the GSH is converted into GSSG to stop the action of the reactive species in the organism. Since there were no differences in the concentrations of GSH, GSSG and in its relation, our results did not confirm the possible pro-oxidant activity of the beta-carotene. On the contrary, as the beta-carotene itself can only present antioxidant effect, there should be no need of consuming GSH, forming GSSG to keep the redox balance. Therefore, if we consider that, despite these factors, there was a consistent intensification of the cardiac remodeling with beta-carotene, it may be suggested that the lipoperoxidation probably did not participate in the enhancement of the ventricularremodeling.
It is important to note that the mechanisms involved in the intensification of cardiac remodeling induced by ETS are not known. The present study rules out ventricular geometry as a pivotal modulator of cardiac remodelling induced by smoking. Likewise, although the extracellular matrix plays a critical role in the maintenance of ventricular geometry and function, we found that neither MMP-2 nor MMP-9 participate in ventricularremodeling induced by tobacco smoke exposure. 24 Previous investigations did not show alterations
exercise performed prior to MI showed no reduction in infarction size or attenuation of the myocardial remodeling process in animals studied seven days after coronary occlusion. To the best of our knowledge, there are no studies that evaluated the influence of exercise on late ventricularremodeling. Therefore, the aim of this study was to evaluate the late cardiac structural and functional effects in rats undergoing physical exercise followed by acute myocardial infarction.
findings are derived from a cross-sectional study and we cannot infer causality, but only an independent association between OSA and heart remodeling. The fact that we could not demonstrate the same atrial and ventricularremodeling findings in the subgroup of patients with the indeterminate form of CD could be due to the small number of patients in this category. Moreover, the absence of increased incidence of arrhythmias in OSA patients in this study should be analyzed with caution, as 24 h Holter monitoring could not detect intermittent arrhythmias. New studies with technologies that analyze long periods of time are warranted.
Because myocardial fibrosis contributes to the pathology of ventricularremodeling [25,26], we examined whether atorvastatin attenuated myocardial collagen content. As shown in Fig. 6, the myocardial hydroxyproline content in the ischemic and nonisch- emic zones was significantly higher in the vehicle-treated group compared with the atorvastatin-treated group (0.1360.01 vs. 0.0960.02 and 0.1160.01 vs. 0.0560.01 m g/mg wet weight, P,0.05, respectively). In addition, myocardial apoptotic nuclear density (i.e., the percentage of nuclei that were apoptotic) was significantly higher in vehicle-treated compared with atorvastatin- treated hearts (ischemic zone: 2.3560.25% vs. 1.0660.24%; Figure 4. Quantitative assessment of LV remodeling. Panels A–D illustrates echocardiographic measurement of LV AW thickness in diastole (A), LV end-diastolic diameter (B), LV end-diastolic area (C) and LV end-diastolic volume (D) at baseline, 48 hr and 4 wk after myocardial infarction. The administration of atorvastatin improved adverse LV remodeling at 4 wk after myocardial infarction. Data are mean 6 SEM. n = 8–12 rats per group. *, P,0.05 versus vehicle-treated rats at 4 wk. Abbreviations: AW, anterior wall; BSL, baseline; hr, hours; LV, left ventricular.
30. Zhang YM, Lu Y, Tang Y, Yang D, Wu HF, Bian ZP, et al. The effects of different initiation time of exercise training on left ventricularremodeling and cardiopulmonary rehabilitation in patients with left ventricular dysfunction after myocardial infarction – Disabil Rehabil. 2015 May 7:1-9. [Epub ahead of print]. 31. Lyne JC, Pennell DJ. Cardiovascular magnetic resonance in the quantitative assessment of left ventricular mass, volumes and contractile function. Coron Artery Dis. 2005;16(6):337-43.
Methods: 16 patients enrolled according to the following inclusion criteria: normal ventricular function defined by echocardiogram and presence of upper ventricular stimulation > 90% (generator telemetry assessment) submitted to a PM implant were prospectively studied. The following parameters were assessed: Functional Class (FC), walk test, BNP levels, echocardiography evaluation (conventional and intraventricular dyssynchrony) and quality of life test (SF36). The patients were assessed after 10 (t1), 120 (t2) and 240 days (t3). Data was compared throughout time according to ANOVA. Multiple comparisons of means were performed through Tukey’s test.
of life in elderly patients with coronary artery disease . In addition, the other 4 reports of RCT revealed the protective effects of TMZ against left ventricular dysfunction in diabetic patients with ischemic cardiomyopathy [12–14,22]. The cardioprotective effects of TMZ were also evaluated in patients with dilated cardiomyopathy. Tuunanen et al. reported that TMZ enhanced cardiac function and had both cardiac and extracardiac metabolic effects in idiopathic dilated cardiomyopathy with heart failure . Zhao et al. indicated that TMZ treatment was associated with a considerable improvement of cardiac function and physical tolerance in diabetic patients with idiopathic dilated cardiomyop- athy . The pooled results of these studies suggested that TMZ Table 2. Study characteristics.