Effects of lisinopril on experimental ischemia in rats. Influence of infarct size

OBJECTIVE - Angiotensin-converting enzyme inhibitors (ACEIs) have gained importance in preventing or attenuating the process of ventricular remodeling after myocardial infarction. The significance of infarct size in regard to the response to ACEIs, however, is controversial. This study aimed to analyze the effects of lisinopril on mortality rate, cardiac function, degree of cardiac hypertrophy and fibrosis in rats with different infarct sizes. METHODS - Lisinopril (20 mg/kg/day) dissolved in drinking water was administered to rats immediately after coronary artery occlusion. After being sacrificed, the infarcted animals were divided into two groups: one group of animals with small infarcts (< 40% of the left ventricle) and another group of animals with large infarcts (> 40% of the left ventricle). RESULTS - The mortality rate was 31.7% in treated rats and 47% in the untreated rats. There was no statistical difference between the groups with small and large infarcts in regard to myocardial concentration of hydroxyproline. In small infarcts, the treatment attenuated the heart dysfunction characterized by lower levels of blood pressure and lower values of the first derivative of pressure and of the negative derivative of pressure. The degree of hypertrophy was also attenuated in small infarcts. In regard to large infarcts, no differences between the groups were observed. CONCLUSION - Treatment with the ACEIs had no effect on mortality rate and on the amount of fibrosis. The protective effect of lisinopril on heart function and on the degree of hypertrophy could only be detected in small infarcts

Infarct Size as Predictor of Systolic Functional Recovery after Myocardial Infarction

Background: The effects of modern therapy on functional recovery after acute myocardial infarction (AMI) are unknown.Objectives: To evaluate the predictors of systolic functional recovery after anterior AMI in patients undergoing modern therapy (reperfusion, aggressive platelet antiaggregant therapy, angiotensin-converting enzyme inhibitors and beta-blockers).Methods: A total of 94 consecutive patients with AMI with ST-segment elevation were enrolled. Echocardiograms were performed during the in-hospital phase and after 6 months. Systolic dysfunction was defined as ejection fraction value < 50%.Results: In the initial echocardiogram, 64% of patients had systolic dysfunction. Patients with ventricular dysfunction had greater infarct size, assessed by the measurement of total and isoenzyme MB creatine kinase enzymes, than patients without dysfunction. Additionally, 24.5% of patients that initially had systolic dysfunction showed recovery within 6 months after AMI. Patients who recovered ventricular function had smaller infarct sizes, but larger values of ejection fraction and E-wave deceleration time than patients without recovery. At the multivariate analysis, it can be observed that infarct size was the only independent predictor of functional recovery after 6 months of AMI when adjusted for age, gender, ejection fraction and E-wave deceleration time.Conclusion: In spite of aggressive treatment, systolic ventricular dysfunction remains a frequent event after the anterior myocardial infarction. Additionally, 25% of patients show functional recovery. Finally, infarct size was the only significant predictor of functional recovery after six months of acute myocardial infarction.

Early rather than delayed administration of lisinopril protects the heart after myocardial infarction in rats

Background: ACE inhibitors have shown beneficial results in several studies after myocardial infarction (MI). However, these studies have shown conflicting results about the ideal starting time of the ACE inhibitors administration after MI and the importance of infarct size.Objectives: This study was designed to assess the long-term effects of lisinopril on mortality, cardiac function, and ventricular fibrosis after MI, in rats.Methods: Lisinopril (20 mg/kg/day) was given on day 1 or 21 days after coronary occlusion in small or large infarctions.Results: the mortality rate was reduced by 39% in early treatment and 30% in delayed treatment in comparison to the untreated rats. Early treatment reduced cardiac dysfunction in small MIs; however, delayed treatment did not. No statistical difference was observed among the groups for large MIs. No statistical difference was observed among the groups with large or small MIs on myocardial hydroxyproline concentration.Conclusions: Both early and delayed treatments with lisinopril increased survival. Treatment exerts no marked effects on fibrosis; early treatment has exerted beneficial influences on cardiac function whereas delayed treatment had no consistent effects. The protective effect of lisinopril is detectable only in small (< 40% of LV) MIs.

Comparação de diferentes métodos para medida do tamanho do infarto experimental crônico em Ratos

OBJETIVO: Avaliar as diferenças entre três métodos para medida do infarto experimental em ratos, em relação ao método tradicional. MÉTODOS: A área infartada por histologia (AREA), o perímetro interno da cavidade infartada por histologia (PER) e o perímetro interno por ecocardiograma (ECO) foram comparados ao método tradicional (análise histológica das circunferências epicárdicas e endocárdicas da região infartada - CIR). Utilizaram-se ANOVA de medidas repetidas, complementada com o teste de comparações múltiplas de Dunn, o método de concordância de Bland & Altman e o teste de correlação de Spearman. A significância foi p < 0,05. RESULTADOS: Foram analisados dados de 122 animais, após 3 a 6 meses do infarto. Houve diferença na avaliação do tamanho do infarto entre CIR e os outros três métodos (p < 0,001): CIR = 42,4% (35,9-48,8), PER = 50,3% (39,1-57,0), AREA = 27,3% (20,2-34,3), ECO = 46,1% (39,9-52,6). Assim, a medida por área resultou em subestimação de 15% do tamanho do infarto, enquanto as medidas por ecocardiograma e pelo perímetro interno por meio de histologia resultaram em superestimação do tamanho do infarto de 4% e 5%, respectivamente. em relação ao ECO e PER, apesar de a diferença entre os métodos ser de apenas 1,27%, o intervalo de concordância variou de 24,1% a -26,7%, sugerindo baixa concordância entre os métodos. em relação às associações, houve correlações estatisticamente significativas entre: CIR e PER (r = 0,88 e p < 0,0001); CIR e AREA (r = 0,87 e p < 0,0001) e CIR e ECO (r = 0,42 e p < 0,0001). CONCLUSÃO: Na determinação do tamanho do infarto, apesar da alta correlação, houve baixa concordância entre os métodos.

Relação entre a esfericidade, a função ventricular e o tamanho do infarto em ratos

FUNDAMENTO: A esfericidade do ventrículo esquerdo (VE) é fator associado com disfunção ventricular, mas não está bem caracterizada no modelo de ratos infartados. OBJETIVO: Analisar a relação entre o índice de esfericidade, a função ventricular e a área infartada no modelo experimental em ratos. MÉTODOS: Seis meses após infarto (IAM, n=33) ou cirurgia simulada (SHAM, n=18), os animais foram submetidos a ecocardiograma. O índice de esfericidade foi obtido pela razão entre as áreas diastólicas nos eixos maior e menor do VE. RESULTADOS: O grupo IAM apresentou menor índice de esfericidade (1,32 × 0,23 vs 1,57 × 0,33; p=0,002), de função sistólica e espessura relativa (0,13 × 0,003 vs 0,18 × 0,04; p<0,001) e maior índice de estresse parietal (1,27 × 0,33 vs 0,88 × 0,25; p<0,001). Houve correlação significativa entre tamanho do infarto e esfericidade (p=0,046). Na análise de regressão linear, o tamanho de infarto (p=0,014), mas não a esfericidade (p=0,683) e o estresse parietal (p=0,176), foi fator de predição da função sistólica. Remodelação excêntrica (p=0,011), mas não a esfericidade (p=0,183) ou o tamanho de infarto (p=0,101), foi fator preditor do estresse parietal. Adicionalmente, o tamanho do infarto (p=0,046), mas não remodelação excêntrica (0,705), foi fator preditor da esfericidade. O tamanho do infarto (p=0,015) e o estresse parietal (p=0,011), mas não a esfericidade (p=0,705), foram preditores de remodelação excêntrica. CONCLUSÃO: A esfericidade está associada mas não é fator determinante do estresse parietal, da remodelação excêntrica e da função sistólica ventricular no modelo de infarto experimental em ratos.

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.

Predictors of Right Ventricle Dysfunction After Anterior Myocardial Infarction

Background: Regardless significant therapeutic advances, mortality and morbidity after myocardial infarction (MI) are still high. For a long time, the importance of right ventricle (RV) function has been neglected. Recently, RV dysfunction has also been associated with poor outcomes in the setting of heart failure. The shape, location, and contraction conditions make the RV chamber assessment technically challenging.Methods: Our study identified clinical characteristics and left ventricle (LV) echocardiographic data performed 3-5 days after MI that could be associated with RV dysfunction (RV fractional area change [FAC] < 35%) 6 months after MI.Results: The RV dysfunction group consisted of 11 patients (RV FAC 29.4% +/- 5.2) and the no RV dysfunction group of 71 patients (RV FAC 43.7% +/- 5.1); (P < 0.001). Both groups presented the same baseline clinical characteristics. Left atrium (LA), interventricular septum (IVS), and left ventricular posterior wall (LVPW) were larger in RV dysfunction than in no RV dysfunction. Conversely, E wave deceleration time (EDT) was lower in RV dysfunction when compared with no RV dysfunction. Left atrium(adj) (adjusted by gender, age, infarct size, and body mass index) (odds ratio [OR], 1.22; confidence interval [CI], 1.016-1.47; P = 0.032), interventricular septum(adj) (OR, 1.49; CI, 1.01-2.23; P = 0.044), and E wave deceleration time(adj) (OR, 0.98; CI, 0.97-0.98; P = 0.029) assessed soon after MI predicted RV failure after 6-months.Conclusions: LV diastolic dysfunction, resulting from anterior MI and assessed 3-5 days after the event, may play an important role in predicting RV dysfunction 6 months later.

Heart Failure After Myocardial Infarction: Clinical Implications and Treatment

Heart failure is a frequent complication of myocardial infarction. Several factors, such as recurrent myocardial ischemia, infarct size, ventricular remodeling, stunned myocardium, mechanical complications, and hibernating myocardium influence the appearance of left ventricular systolic dysfunction after myocardial infarction. Importantly, its presence increases the risk of death by at least 3- to 4-fold. The knowledge of the mechanisms and clinical features are essential for the diagnosis and treatment of left ventricular dysfunction and heart failure after myocardial infarction. Therefore, this review will focus on the clinical implications and treatment of heart failure after myocardial infarction.

Echocardiographic detection of congestive heart failure in postinfarction rats

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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

Use of impedance spectroscopy in the study of the effect of Cr concentration on the electrical properties of SnO2-based ceramics

This paper reports a study of influence of Cr concentration on the electrical properties and microstructure of SnO2-based powders doped with Mn and Nb, prepared by an organic route (Pechini method). All the samples were compacted into discs and sintered at 1300 degrees C for 3h, resulting in ceramics with relative density varying between 78% and 98%. The powders were characterized by X-ray diffraction analysis. Impedance spectroscopy characterization indicated that the conductivity decreases as Cr concentration increases, probably due to Cr segregation at grain boundaries, which reduces grain size, increasing the number of resistive boundaries.

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.

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.

Echocardiographic predictors of ventricular remodeling after acute myocardial infarction in rats

Background: The prediction of the ventricular remodeling process after acute myocardial infarction (AMI) may have important clinical implications. Objetive: To analyze echocardiographic variables predictors of remodeling in the infarction model in rats. Methods: The animals underwent echocardiography in two moments, five days and three months after infarction (AMI group) or sham surgery (control group). Linear regression was used to identify the echocardiographic variables on the fifth day after the infarction, which were predictive of remodeling after three months of coronary occlusion. We considered as a criterion of remodeling in this study, the values of left ventricular diastolic diameter (LVDD) after three months of infarction. Results: The infarction induced increase in the left chambers, associated with changes in systolic and diastolic functions. The variables body weight, left ventricular wall stress index (LVWSI), systolic area (SA), diastolic area (DA), LVDD, left ventricular systolic diameter (LVSD), fractional area change (FAC), ejection fraction (EF), fractional shortening (%Short), posterior wall shortening velocity (PWSV) and infarct size assessed five days after infarction were predictors of LVDD after three months. At the multivariate regression analysis, we included the size of infarction, the LVWSI and PWSV. The LVWSI (coefficient: 4.402, standard error: 2.221, p = 0.05), but not the size of infarction and PWSV, was a predictor of remodeling after three months of infarction. Conclusion: LVPSI was an independent predictor of remodeling three months after the myocardial infarction and could be included in the clinical stratification after the coronary occlusion.