Prevalence and predictors of ventricular remodeling after anterior myocardial infarction in the era of modern medical therapy

Background: The consequences of aggressive therapy following a myocardial infarction (MI) on ventricular remodeling are not well established. Thus, the objective of this study was to analyze the prevalence, clinical characteristics, and predictors of left ventricular remodeling in the era of modern medical therapy.Material/Methods: Clinical characteristics and echocardiographic data were analyzed in 66 consecutive patients with anterior infarction at admission and at 6-month follow-up. Ventricular remodeling was defined as an increase of 10% in ventricular end-systolic or end-diastolic diameter.Results: In our study, 58% of patients presented with ventricular remodeling. Patients with remodeling possessed higher total plasma creatine kinase (CPK), MB-fraction (CPK-MB), heart rate, heart failure, shortness of breath, and reperfusion therapy than patients without remodeling. In contrast, patients with remodeling had a smaller ejection fraction, E-Wave deceleration time (EDT), and early (E' Wave) and late (A' Wave) diastolic mitral annulus velocity (average of septal and lateral walls), but a higher E/E' than patients without remodeling. Patients with remodeling used more diuretics, digoxin, oral anticoagulants and aldosterone antagonists than patients without remodeling. In the multivariate analyses, only E' Wave was an independent predictor of ventricular remodeling. Each 1 unit increase in the E' Wave was associated with a 59% increased odds of ventricular remodeling.Conclusions: In patients with anterior MI, despite contemporary treatment, ventricular remodeling is still a common event. In addition, diastolic function can have an important role as a predictor of remodeling in this scenario.

Doppler Echocardiographic Assessment of Pregnant Women with Chronic Arterial Hypertension

OBJECTIVE: To assess structural and functional cardiac changes in asymptomatic pregnant women with chronic arterial hypertension (CAH). METHODS: One hundred pregnant women with CAH underwent conventional Doppler echocardiography. The Student t test was used to compare them with 29 normotensive pregnant women (NT) in their third gestational trimester. RESULTS: Systolic (SBP; mmHg) and diastolic (DBP; mmHg) blood pressure values were higher (p<0.001) in the CAH pregnant women (SBP: 139±19 and DBP: 92± 18) as compared with those of the NT group (SBP: 112±10 and DBP: 74±9). A significant enlargement of the left atrium (4.10±0.48 cm vs 3.6±0.3 cm; p<0.001) and of the left ventricular normalized mass (59.6±19.7 g/cm2,7 vs 41.9±3.4 g/cm2,7; p<0.001) was observed. Cardiac output (CO, L/min) and systolic volume (SV, mL) were significantly higher in the CAH group (CO: 6.0±1.54 vs 4.9±2.1, p<0.01; SV: 77.3±19.8 vs 56.5±25.8, p<0.001). CONCLUSION: Chronic hypertensive pregnant women have structural and functional cardiac changes that justify routine cardiologic assessment, even in the absence of cardiopulmonary symptoms.

Food restriction impairs myocardial inotropic response to calcium and beta-adrenergic stimulation in spontaneously hypertensive rats

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

Cardiac remodeling in a rat model of diet-induced obesity

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

Growth hormone attenuates skeletal muscle changes in experimental chronic heart failure

Objective: This study evaluated the effects of growth hormone (GH) on morphology and myogenic regulatory factors (MRF) gene expression in skeletal muscle of rats with ascending aortic stenosis (AAS) induced chronic heart failure.Design: Male 90-100 g Wistar rats were subjected to thoracotomy. AAS was created by placing a stainless-steel clip on the ascending aorta. Twenty five weeks after surgery, rats were treated with daily subcutaneous injections of recombinant human GH (2 mg/kg/day; AAS-GH group) or saline (AAS group) for 14 days. Sham-operated animals served as controls. Left ventricular (LV) function was assessed before and after treatment. IGF-1 serum levels were measured by ELISA. After anesthesia, soleus muscle was frozen in liquid nitrogen. Histological sections were stained with HE and picrosirius red to calculate muscle fiber cross-sectional area and collagen fractional area, respectively. MRF myogenin and MyoD expression was analyzed by reverse transcription PCR.Results: Body weight was similar between groups. AAS and AAS-GH groups presented dilated left atrium, left ventricular (LV) hypertrophy (LV mass index: Control 1.90 +/- 0.15; AAS 3.11 +/- 0.44; AAS-GH 2.94 +/- 0.47 g/kg; p < 0.05 AAS and AAS-GH vs. Control), and reduced LV posterior wall shortening velocity. Soleus muscle fiber area was significantly lower in AAS than in Control and AAS-GH groups; there was no difference between AAS-GH and Control groups. Collagen fractional area was significantly higher in MS than Control; AAS-GH did not differ from both Control and AAS groups. Serum IGF-1 levels decreased in AAS compared to Control. MyoD mRNA was significantly higher in AAS-GH than AAS; there was no difference between AAS-GH and Control groups. Myogenin mRNA levels were similar between groups.Conclusion: In rats with aortic stenosis-induced heart failure, growth hormone administration increases MyoD gene expression above non-treated animal levels, preserves muscular trophism and attenuates interstitial fibrosis. These results suggest that growth hormone may have a potential role as an adjuvant therapy for chronic heart failure. (C) 2009 Elsevier Ltd. All rights reserved.

Ventricular Remodeling Induced by Tissue Vitamin A Deficiency in Rats

Background/Aims: Experimental studies suggest that vitamin A plays a role in regulating cardiac structure and function. We tested the hypothesis that cardiac vitamin A deficiency is associated with adverse myocardial remodeling in young adult rats. Methods: Two groups of young female rats, control (C - n = 29) and tissue vitamin A deficient (RVA - n = 31), were subjected to transthoracic echocardiography exam, isolated rat heart study and biochemical study. Results: The RVA rats showed a reduced total vitamin A concentration in both the liver and heart [vitamin A in heart, mu mol/kg (C = 0.95 +/- 0.44 and RVA = 0.24 +/- 0.16, p = 0.01)] with the same serum retinol levels (C = 0.73 +/- 0.29 mu mol/L e RVA = 0.62 +/- 0.17 mu mol/L, p = 0.34). The RVA rats showed higher left ventricular diameters and reduced systolic function. The RVA rats also demonstrated increased lipid hydroperoxide/total antioxidant capacity ratio and cardiac levels of IFN-gamma and TNF-alpha but not of metalloproteinase (MMP)-2 and -9 activity. on the other hand, the RVA rats had decreased levels of beta-hydroxyacylcoenzyme A dehydrogenase and lactate dehydrogenase. Conclusions: Tissue vitamin A deficiency stimulated cardiac remodeling and ventricular dysfunction. Additionally, the data support the involvement of oxidative stress, energy metabolism, and cytokine production in this remodeling process. Copyright (C) 2010 S. Karger AG, Basel

Influence of different doses of retinoic acid on cardiac remodeling

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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

Aldosterone is not Involved in the Ventricular Remodeling Process Induced by Tobacco Smoke Exposure

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

End-systolic pressure-diameter relation of the left ventricle during transient and sustained elevations of blood pressure

OBJECTIVE: To assess the effect of transient and sustained variations in cardiac load on the values of the end-systolic pressure-diameter relation (ESPDR) of the left ventricle. METHODS: We studied 13 dogs under general anesthesia and autonomic blockade. Variations of cardiac loads were done by elevation of blood pressure by mechanical constriction of the aorta. Two protocols were used in each animal: gradual peaking and decreasing pressure variation, the transient arterial hypertension protocol (TAH), and a quick and 10 min sustained elevation, the sustained arterial hypertension protocol(SAH). Then, we compared the ESDR in these two situations. RESULTS: Acute elevation of arterial pressure, being it transitory or sustained, did not alter the heart frequency and increased similarly the preload and after load. However, they acted differently in end systolic pressure-diameter relation. It was greater in the SAH than TAH protocol, 21.0±7.3mmHg/mm vs. 9.2±1.2mmHg/mm (p<0.05). CONCLUSION: The left ventricular ESPDR values determined during sustained pressure elevations were higher than those found during transient pressure elevations. The time-dependent activation of myocardial contractility associated with the Frank-Starling mechanism is the major factor in inotropic stimulation during sustained elevations of blood pressure, determining an increase in the ESPDR values.

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 and diastolic myocardial dysfunction in rats submitted to protein-calorie malnutrition

The effects of protein-calorie malnutrition (PCM) on heart structure and function are not completely understood. We studied heart morphometric, functional, and biochemical characteristics in undernourished young Wistar rats. They were submitted to PCM from birth (undernourished group, UG). After 10 wk, left ventricle function was studied using a Langendorff preparation. The results were compared with age-matched rats fed ad libitum (control group, CG). The UG rats achieved 47% of the body weight and 44% of the left ventricular weight (LVW) of the CG. LVW-to-ventricular volume ratio was smaller and myocardial hydroxyproline concentration was higher in the UG. Left ventricular systolic function was not affected by the PCM protocol. The myocardial stiffness constant was greater in the UG, whereas the end-diastolic pressure-volume relationship was not altered. In conclusion, the heart is not spared from the adverse effects of PCM. There is a geometric alteration in the left ventricle with preserved ventricular compliance despite the increased passive myocardial stiffness. The systolic function is preserved.

Volume overload influence on hypertrophied myocardium function

The aim of this study was to demonstrate that hypertrophied cardiac muscle is more sensitive to volume-overload than normal cardiac muscle. We assessed the mechanical function of isolated left ventricular papillary muscle from male spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY) Submitted to volume overload caused by aortocaval fistula (ACF) for 30 days. Muscles were perfused with Krebs-Henseleit solution at 28degreesC and Studied isometrically at a Stimulation rate of 0.2 Hz. The ACF increased the right and left ventricular weight-to-body weight ratio in WKY rats; it also promoted right ventricular hypertrophy and further increased the basal hypertrophy in the left ventricle from SHR. The arterial systolic pressure was greater in SHR than in WKY rats, and decreased with ACF in both groups. Developed tension (DT) and maximum rate of DT (+dT/dt) were greater in the SHR-control than in the WKY-control (P<0.05); the time from peak tension to 50% relaxation (RT1/2) was similar in these animals. ACE did not change any parameters ill the SHR group and increased the resting tension in the WKY group. However, the significant difference observed between myocardial contraction performance in WKY-controls and SHR-controls disappeared when the SHR-ACF and WKY-controls were compared. Furthermore, RT1/2 increased significantly ill the SHR-ACF in relation to the WKY-controls. In conclusion, the data lead LIS to infer that volume-overload for 30 days promotes more mechanical functional changes in hypertrophied muscle than in normal cardiac muscle.

Myocardial function during chronic food restriction in isolated hypertrophied cardiac muscle

Background: the effect of food restriction (FR) on myocardial performance has been studied in normal hearts. Few experiments analyzed the effects of undernutrition on hearts subjected to cardiac overload. The aim of this study was to determine whether chronic FR promotes more significant changes in hypertrophied hearts than in normal hearts. Methods: Myocardial performance was studied in isolated left ventricular papillary muscle from young male spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY) submitted to FR or to control diet. The animals subjected to FR were fed 50% of the amount of food consumed by control groups for 60 days. Isolated muscles were studied while contracting isometrically and isotonically. Results: FR decreased the body weight and the left ventricular weight in both groups. FR increased the left ventricular weight-to-body weight ratio in the WKY rats and tended to decrease this ratio in SHR (P = 0.055). The arterial systolic pressure was greater in SHR than in WKY groups and did not change with FR. In the animals with normal diet, myocardial performance was better in SHR than in WKY. FR increased time to tension to fall from peak to 50% of peak tension and time to peak tension in the WKY rats and time to peak tension in the SHR. Conclusions: FR for 60 days has a trend to attenuate the development of cardiac hypertrophy and does not promote more mechanical functional changes in the hypertrophied myocardium than in the normal cardiac muscle.