Mecánica ventricular izquierda en pacientes con infarto agudo del miocardio

RESUMEN Introducción El papel de las nuevas técnicas ecocardiográficas para el diagnóstico de infarto agudo del miocardio se encuentra en desarrollo y la realización de mecánica ventricular izquierda podría sugerir la presencia de enfermedad coronaria hemodinámicamente significativa. Objetivos Determinar si en pacientes con infarto agudo del miocardio la medición de strain longitudinal global y regional sirve para predecir la presencia de enfermedad coronaria significativa. Métodos Es un estudio de pruebas diagnósticas en el que se evaluaron las características operativas de la mecánica ventricular izquierda para la detección de enfermedad coronaria significativa comparado contra el cateterismo cardiaco, considerado el patrón de oro. Se analizaron 54 pacientes con infarto agudo del miocardio llevados a cateterismo cardiaco, a quienes se les realizó un ecocardiograma transtorácico con medición de strain longitudinal global y regional. Resultados De los 54 pacientes analizados, el 83% tenía enfermedad coronaria significativa. El hallazgo de un strain longitudinal global < -17.5 tuvo una sensibilidad del 85% y una especificidad del 78% para predecir la presencia de enfermedad coronaria; para la arteria descendente anterior un strain longitudinal regional < – 17.4 tuvo una sensibilidad de 82% y una especificidad de 44%, para la arteria circunfleja una sensibilidad del 87% y una especificidad del 37% y para la arteria coronaria derecha una sensibilidad de 73% y una especificidad de 32%. Conclusiones La realización de ecocardiografía con mecánica ventricular en pacientes con infarto agudo del miocardio es útil para predecir la presencia de enfermedad coronaria hemodinámicamente significativa.

Targeting C-reactive protein for the treatment of cardiovascular disease

Complement-mediated inflammation exacerbates the tissue injury of ischaemic necrosis in heart attacks and strokes, the most common causes of death in developed countries. Large infarct size increases immediate morbidity and mortality and, in survivors of the acute event, larger non-functional scars adversely affect long-term prognosis. There is thus an important unmet medical need for new cardioprotective and neuroprotective treatments. We have previously shown that human C-reactive protein (CRP), the classical acute-phase protein that binds to ligands exposed in damaged tissue and then activates complement(1), increases myocardial and cerebral infarct size in rats subjected to coronary or cerebral artery ligation, respectively(2,3). Rat CRP does not activate rat complement, whereas human CRP activates both rat and human complement(4). Administration of human CRP to rats is thus an excellent model for the actions of endogenous human CRP2,3. Here we report the design, synthesis and efficacy of 1,6-bis(phosphocholine)-hexane as a specific small-molecule inhibitor of CRP. Five molecules of this palindromic compound are bound by two pentameric CRP molecules, crosslinking and occluding the ligand-binding B-face of CRP and blocking its functions. Administration of 1,6-bis(phosphocholine)-hexane to rats undergoing acute myocardial infarction abrogated the increase in infarct size and cardiac dysfunction produced by injection of human CRP. Therapeutic inhibition of CRP is thus a promising new approach to cardioprotection in acute myocardial infarction, and may also provide neuroprotection in stroke. Potential wider applications include other inflammatory, infective and tissue-damaging conditions characterized by increased CRP production, in which binding of CRP to exposed ligands in damaged cells may lead to complement-mediated exacerbation of tissue injury.

Lipoprotein (a) as a predictor of myocardial infarction in middle-aged men

We found that a high Lp(a) level was an independent predictor of the development of coronary heart disease in middle-aged men.

Lipoma preferred partner is a mechanosensitive protein regulated by nitric oxide in the heart

Adaptor proteins play an important role in signaling pathways by providing a platform on which many other proteins can interact. Malfunction or mislocalization of these proteins may play a role in the development of disease. Lipoma preferred partner (LPP) is a nucleocytoplasmic shuttling adaptor protein. Previous work shows that LPP plays a role in the function of smooth muscle cells and in atherosclerosis. In this study we wanted to determine whether LPP has a role in the myocardium. LPP expression increased by 56% in hearts from pressure overload aortic-banded rats (p < 0.05 n = 4), but not after myocardial infarction, suggesting hemodynamic load regulates its expression. In vitro, LPP expression was 87% higher in cardiac fibroblasts than myocytes (p < 0.05 n = 3). LPP expression was downregulated in the absence of the actin cytoskeleton but not when microtubules were disassembled. We mechanically stretched cardiac fibroblasts using the Flexcell 4000 for 48 h (1 Hz, 5% maximum strain), which decreased total LPP total expression and membrane localization in subcellular fractions (p < 0.05, n = 5). However, L-NAME, an inhibitor of nitric oxide synthase (NOS), significantly upregulated LPP expression. These findings suggest that LPP is regulated by a complex interplay between NO and mechanical cues and may play a role in heart failure induced by increased hemodynamic load.

Marine omega-3 fatty acids and coronary heart disease

Purpose of review: To provide an overview of the key earlier intervention studies with marine omega-3 fatty acids and to review and comment on recent studies reporting on mortality outcomes and on selected underlying mechanisms of action. Recent findings: Studies relating marine omega-3 fatty acid status to current or future outcomes continue to indicate benefits, for example, on incident heart failure, congestive heart failure, acute coronary syndrome, and all-cause mortality. New mechanistic insights into the actions of marine omega-3 fatty acids have been gained. Three fairly large secondary prevention trials have not confirmed the previously reported benefit of marine omega-3 fatty acids towards mortality in survivors of myocardial infarction. Studies of marine omega-3 fatty acids in atrial fibrillation and in cardiac surgery-induced atrial fibrillation have produced inconsistent findings and meta-analyses demonstrate no benefit. A study confirmed that marine omega-3 fatty acids reduce the inflammatory burden with advanced atherosclerotic plaques, so inducing greater stability. Summary: Recent studies of marine omega-3 fatty acids on morbidity of, and mortality from, coronary and cardiovascular disease have produced mixed findings. These studies raise new issues to be addressed in future research.

Absence of association between the INSIG2 gene polymorphism (rs7566605) and obesity in the European Youth Heart Study (EYHS)

The first genome-wide association study for BMI identified a polymorphism, rs7566605, 10 kb upstream of the insulin-induced gene 2 (INSIG2) transcription start site, as the most significantly associated variant in children and adults. Subsequent studies, however, showed inconsistent association of this polymorphism with obesity traits. This polymorphism has been hypothesized to alter INSIG2 expression leading to inhibition of fatty acid and cholesterol synthesis. Hence, we investigated the association of the INSIG2 rs7566605 polymorphism with obesity- and lipid-related traits in Danish and Estonian children (930 boys and 1,073 girls) from the European Youth Heart Study (EYHS), a school-based, cross-sectional study of pre- and early pubertal children. The association between the polymorphism and obesity traits was tested using additive and recessive models adjusted for age, age-group, gender, maturity and country. Interactions were tested by including the interaction terms in the model. Despite having sufficient power (98%) to detect the previously reported effect size for association with BMI, we did not find significant effects of rs7566605 on BMI (additive, P = 0.68; recessive, P = 0.24). Accordingly, the polymorphism was not associated with overweight (P = 0.87) or obesity (P = 0.34). We also did not find association with waist circumference (WC), sum of four skinfolds, or with total cholesterol, triglycerides, low-density lipoprotein, or high-density lipoprotein. There were no gender-specific (P = 0.55), age-group-specific (P = 0.63) or country-specific (P = 0.56) effects. There was also no evidence of interaction between genotype and physical activity (P = 0.95). Despite an adequately powered study, our findings suggest that rs7566605 is not associated with obesity-related traits and lipids in the EYHS.

Effects of exercise training on autonomic dysfunction management in an experimental model of menopause and myocardial infarction

Objective: The aim of this study was to investigate the effects of exercise training on cardiovascular autonomic dysfunction in ovariectomized rats submitted to myocardial infarction. Methods: Female Wistar rats were divided into the following ovariectomized groups: sedentary ovariectomized (SO), trained ovariectomized (TO), sedentary ovariectomized infarcted (SOI), and trained ovariectomized infarcted (TOI). Trained groups were submitted to an exercise training protocol on a treadmill (8 wk). Arterial baroreflex sensitivity was evaluated by heart rate responses to arterial pressure changes, and cardiopulmonary baroreflex sensitivity was tested by bradycardic and hypotension responses to serotonin injection. Vagal and sympathetic effects were calculated by pharmacological blockade. Results: Arterial pressure was reduced in the TO in comparison with the SO group and increased in the TOI in relation to the SOI group. Exercise training improved the baroreflex sensitivity in both the TO and TOI groups. The TOI group displayed improvement in cardiopulmonary reflex sensitivity compared with the SOI group at the 16 mu g/kg serotonin dose. Exercise training enhanced the vagal effect in both the TO (45%) and TOI (46%) animals compared with the SO and SOI animals and reduced the sympathetic effect in the TOI (38%) in comparison with the SOI animals. Significant correlations were obtained between bradycardic baroreflex responses and vagal (r = -0.7, P < 0.005) and sympathetic (r = 0.7, P < 0.001) effects. Conclusions: These results indicate that exercise training in ovariectomized rats submitted to myocardial infarction improves resting hemodynamic status and reflex control of the circulation, which may be due to an increase in the vagal component. This suggests a homeostatic role for exercise training in reducing the autonomic impairment of myocardial infarction in postmenopausal women.

Autonomic impairment after myocardial infarction: Role in cardiac remodelling and mortality

P>1. Impairmant of baroreflex sensitivity (BRS) has been implicated in the reduction of heart rate variability (HRV) and in the increased risk of death after myocardial infarction (MI). In the present study, we investigated whether the additional impairment in BRS induced by sinoaortic baroreceptor denervation (SAD) in MI rats is associated with changes in the low-frequency (LF) component of HRV and increased mortality rate. 2. Rats were randomly divided into four groups: control, MI, denervated (SAD) and SAD + MI rats. Left ventricular (LV) function was evaluated by echocardiography. Autonomic components were assessed by power spectral analysis and BRS. 3. Myocardial infarction (90 days) reduced ejection fraction (by similar to 42%) in both the MI and SAD + MI groups; however, an increase in LV mass and diastolic dysfunction were observed only in the SAD + MI group. Furthermore, BRS, HRV and the LF power of HRV were reduced after MI, with an exacerbated reduction seen in SAD + MI rats. The LF component of blood pressure variability (BPV) was increased in the MI, SAD and SAD + MI groups compared with the control group. Mortality was higher in the MI groups compared with the non-infarcted groups, with an additional increase in mortality in the SAD + MI group compared with the MI group. Correlations were obtained between BRS and the LF component of HRV and between LV mass and the LF component of BPV. 4. Together, the results indicate that the abolishment of BRS induced by SAD in MI rats further reduces the LF band of HRV, resulting in a worse cardiac remodelling and increased mortality in these rats. These data highlight the importance of this mechanism in the prognosis of patients after an ischaemic event.

Exercise changes the size of cardiac neurons and protects them from age-related neurodegeneration

Aging leads to changes in cardiac structure and function. Evidence suggests that the practice of regular exercise may prevent disturbances in the cardiovascular system during aging. We studied the effects of aging on the morphology and morphometry of cardiac neurons in Wistar rats and investigated whether a lifelong moderate exercise program could exert a protective effect toward some deleterious effects of aging. Aging caused a significant decline (28%) in the number of NADH-diaphorase-stained cardiac Animals submitted to a daily session of 60 min, 5 day/week, at 1.1 km/h of running in treadmill over the entire life span exhibited a reversion of the observed decline in the number of cardiac neurons. However, most interesting was that the introduction of this lifelong exercise protocol dramatically altered the sizes of cardiac neurons. There was a notable increase in the percentage of small neurons in the rats of the exercise group compared to the sedentary animals. This is the first time that a protective effect of lifelong regular aerobic exercise has been demonstrated on the deleterious effects of aging in cardiac neurons. (C) 2009 Elsevier GmbH. All rights reserved.

Neuromuscular electrical stimulation improves GLUT-4 and morphological characteristics of skeletal muscle in rats with heart failure

Aim: Changes in skeletal muscle morphology and metabolism are associated with limited functional capacity in heart failure, which can be attenuated by neuromuscular electrical stimulation (ES). The purpose of the present study was to analyse the effects of ES upon GLUT-4 protein content, fibre structure and vessel density of the skeletal muscle in a rat model of HF subsequent to myocardial infarction. Methods: Forty-four male Wistar rats were assigned to one of four groups: sham (S), sham submitted to ES (S+ES), heart failure (HF) and heart failure submitted to ES (HF+ES). The rats in the ES groups were submitted to ES of the left leg during 20 days (2.5 kHz, once a day, 30 min, duty cycle 50%- 15 s contraction/15 s rest). After this period, the left tibialis anterior muscle was collected from all the rats for analysis. Results: HF+ES rats showed lower values of lung congestion when compared with HF rats (P = 0.0001). Although muscle weight was lower in HF rats than in the S group, thus indicating hypotrophy, 20 days of ES led to their recovery (P < 0.0001). In both groups submitted to ES, there was an increase in muscle vessel density (P < 0.04). Additionally, heart failure determined a 49% reduction in GLUT-4 protein content (P < 0.03), which was recovered by ES (P < 0.01). Conclusion: In heart failure, ES improves morphological changes and raises GLUT-4 content in skeletal muscle.

beta-carotene attenuates the paradoxical effect of tobacco smoke on the mortality of rats after experimental myocardial infarction

The objective of this study was to investigate the effects of exposure to tobacco smoke (ETS) in rats that were or were not supplemented with dietary beta-carotene (BC), on ventricular remodeling and survival after myocardial infarction (MI). Rats (n = 189) were allocated to 4 groups: the control group, n = 45; group BC administered 500 mg/kg diet, n = 49, BC supplemented rats; group ETS, n = 55, rats exposed to tobacco smoke; and group BC+ETS, n = 40. Wistar rats weighing 100 g were administered one of the treatments until they weighed 200 to 250 g (similar to 5 wk). The ETS rats were exposed to cigarette smoke for 30 min 4 times/d, in a chamber connected to a smoking device. After reaching a weight of 200-250 g, rats were subjected to experimental MI (coronary artery occlusion) and mortality rates were determined over the next 105 d. In addition, echocardiographic, isolated heart, morphometrical, and biochemical studies were performed. Mortality data were tested using Kaplan-Meyer curves and other data by 2-way ANOVA. Survival rates were greater in the ETS group (58.2%) than in the control (33.3%) (P = 0.001) and BC+ETS rats (30.0%) (P = 0.007). The groups did not differ in the other comparisons. Left ventricular end-diastolic diameter normalized to body weight was greater and maximal systolic pressures were lower in the ETS groups than in non-ETS groups. Previous exposure to tobacco smoke induced a process of cardiac remodeling after MI. There is a paradoxical protector effect with tobacco smoke exposure, characterized by lower mortality, which is offset by BC supplementation.

THE ROLE of OXIDATIVE STRESS and LIPID PEROXIDATION IN VENTRICULAR REMODELING INDUCED BY TOBACCO SMOKE EXPOSURE AFTER MYOCARDIAL INFARCTION

OBJECTIVE: To evaluate the roles of oxidative stress and lipid peroxidation in the ventricular remodeling that is induced by tobacco smoke exposure after myocardial infarction.METHODS: After induced myocardial infarction, rats were allocated into two groups: C (control, n=25) and ETS (exposed to tobacco smoke, n=24). After 6 months, survivors were submitted to echocardiogram and biochemical analyses.RESULTS: Rats in the ETS group showed higher diastolic (C = 1.52 +/- 0.4 mm(2), ETS = 1.95 +/- 0.4 mm(2); p=0.032) and systolic (C = 1.03 +/- 0.3, ETS = 1.36 +/- 0.4 mm(2)/g; p=0.049) ventricular areas, adjusted for body weight. The fractional area change was smaller in the ETS group (C = 30.3 +/- 10.1 %, ETS = 19.2 +/- 11.1 %; p=0.024) and E/A ratios were higher in ETS animals (C = 2.3 +/- 2.2, ETS = 5.1 +/- 2.5; p=0.037). ETS was also associated with a higher water percentage in the lung (C = 4.8 (4.3-4.8), ETS = 5.5 (5.3-5.6); p=0.013) as well as higher cardiac levels of reduced glutathione (C = 20.7 +/- 7.6 nmol/mg of protein, ETS = 40.7 +/- 12.7 nmol/mg of protein; p=0.037) and oxidized glutathione (C = 0.3 +/- 0.1 nmol/g of protein, ETS = 0.9 +/- 0.3 nmol/g of protein; p=0.008). No differences were observed in lipid hydroperoxide levels (C = 0.4 +/- 0.2 nmol/mg of tissue, ETS = 0.1 +/- 0.1 nmol/mg of tissue; p=0.08).CONCLUSION: In animals exposed to tobacco smoke, oxidative stress is associated with the intensification of ventricular re-remodeling after myocardial infarction.

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.

Influence of AIN-93 diet on mortality and cardiac remodeling after myocardial infarction in rats

Background: The AIN-93 diet was proposed by the American Institute of Nutrition with the objective of standardising studies in experimental nutrition. Our objective was to analyze the effects of AIN-93 diet after myocardial infarction in rats.Methods: Post weaning, the animals were divided into two groups: control (C, n=62), fed the standard diet of our laboratory (Labina); AIN-93 Group (n=70), fed the AIN-93 diet. Achieving 250 g, the animals were subjected to myocardial infarction.Results: Early mortality was increased in AIN-93 animals, associated with lower serum levels of calcium, magnesium, potassium, sodium, and phosphorus. on the other hand, after 90 days, AIN-93 showed smaller normalized left ventricular dimensions. The caloric and carbohydrate intake was smaller, but the fat intake was higher in AIN-93 rats. AIN-93 group also showed increased levels of beta-hydroxyacylcoenzyme A dehydrogenase and citrate synthase. In addition, serum levels of insulin and cardiac levels of malondialdehyde, metalloproteinases-2 and -9, and TNF-alpha and IFN-gamma were decreased in the AIN-93 group.Conclusion: AIN-93 diet increased early mortality, while attenuated the chronic remodeling process after experimental coronary occlusion. Therefore, this diet has biological effects and should be use with attention in this model. (C) 2010 Elsevier B.V. All rights reserved.