Myocardial contractile dysfunction contributes to the development of heart failure in rats with aortic stenosis

Objectives: To analyze the potential contribution of contractility state and ventricular geometry to the development of heart failure in rats with aortic stenosis.Methods: Rats were divided into three groups: compensated aortic stenosis (AS, n = 11), heart failure AS (n = 12) and control rats (C, n = 13).Results: After 21 weeks, failing AS rats presented higher systolic (C = 36.6 +/- 3.1, AS-78.6 +/- 4.8*, failing AS = 104.6 +/- 7.8*) and diastolic meridian stress (C = 6.9 +/- 0.4, AS = 20.1 +/- 1.1*, failing AS = 43.2 +/- 3.2*(dagger)), hydroxyproline (C = 3.6 +/- 0.7 mg/g, AS = 6.6 +/- 0.6* mg/g, failing AS = 9.2 +/- 1.4*(dagger) mg/g) and cross-sectional area (C = 338 +/- 25 mu m(2), AS = 451 +/- 32* mu m(2), failing AS = 508 +/- 36*(dagger) mu m(2)), in comparison with control and compensated AS animals (*p < 0.05 vs. control, (dagger)p < 0.05 vs. AS). In the isometric contraction study, considering the time from peak tension to 50% relaxation (RT50), the relative variation responses, following post-rest contraction and increase in Ca2+ concentration, were higher in failing AS than compensated AS animals. In contrast, following post-rest contraction, compensated AS group presented higher values of the peak developed tension (DT) than failing AS group. Following beta-adrenergic stimulation, control animals presented higher values of +dT/dt and -dT/dt than AS animals. In addition, failing AS animals presented higher TPT values than compensated AS animals.Conclusion: Myocardial contractile dysfunction contributes to the development of heart failure in rats with aortic stenosis. (c) 2006 Elsevier B.V.. All rights reserved.

Heart failure alters matrix metalloproteinase gene expression and activity in rat skeletal muscle

Heart failure is associated with a skeletal muscle myopathy with cellular and extracellular alterations. The hypothesis of this investigation is that extracellular changes may be associated with enhanced mRNA expression and activity of matrix metalloproteinases (MMP). We examined MMP mRNA expression and MMP activity in Soleus (SOL), extensor digitorum longus (EDL), and diaphragm (DIA) muscles of young Wistar rat with monocrotaline-induced heart failure. Rats injected with saline served as age-matched controls. MMP2 and MMP9 mRNA contents were determined by RT-PCR and MMP activity by electrophoresis in gelatin-containing polyacrylamide gels in the presence of SDS under non-reducing conditions. Heart failure increased MMP9 mRNA expression and activity in SOL, EDL and DIA and MMP2 mRNA expression in DIA. These results suggest that MMP changes may contribute to the skeletal muscle myopathy during heart failure.

Mechanical, biochemical, and morphological changes in the heart from chronic food-restricted rats

Food restriction (FR) has been shown to induce important morphological changes in rat myocardium. However, its influence on myocardial performance is not completely defined. We examined the effects of chronic FR on cardiac muscle function and morphology. Sixty-day-old Wistar-Kyoto rats were fed a control (C) or a restricted diet (daily intake reduced to 50% of the amount of food consumed by the control group) for 90 days. Myocardial performance was studied in isolated left ventricular (LV) papillary muscle. Fragments of the LV free wall were analysed by light microscopy, and the ultrastructure of the myocardium was examined in the LV papillary muscle. The myocardial collagen concentration was also evaluated. FR decreased body weight (BW) and LV weight (LVW); the LVW/BW ratio was higher in the restricted group (C, 1.86 +/- 0.17 mg/g; FR, 2.19 +/- 0.31 mg/g; p < 0.01). In the FR animals, the cardiac fibers were polymorphic, some of them were of small diameter and others presented lateral infoldings; the ultrastructural alterations were focal and included reduction of sarcoplasmic content, absence and (or) disorganization of myofilaments and Z line, numerous electron dense and polymorphic mitochondria, and deep infoldings of the plasma membrane. The hydroxyproline concentration was higher in the FR animals (p < 0.01). FR prolonged the contraction and relaxation time of the papillary muscle and did not change its ability to contract and shorten. In conclusion, although a 90-day period of FR caused striking myocardial ultrastructural alterations and increased the collagen concentration, it only minimally affected the mechanical function.

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.

Standardization of an experimental model of parabiotic isolated heart in rabbits

O objetivo foi a padronização de modelo experimental de coração isolado parabiótico em coelhos, testando sua estabilidade e durabilidade, para fins de pesquisa cardiovascular. Foram utilizados 66 coelhos raça Norfolk-2000 divididos em grupo doador do coração isolado e animais suporte, totalizando 33 preparações. Mediante auxilio de bombas peristálticas estabeleceu-se suporte circulatório para o coração isolado mantendo-se fluxo constante(16ml/min.). Um balão intraventricular foi inserido no ventrículo esquerdo, sendo ajustado para gerar pressão diastólica de ± 10mmHg. A freqüência foi fixada em 120 batimentos por minuto mediante o uso de marcapasso. Foram avaliadas variáveis hemodinâmicas, laboratoriais e anatomopatológicas. Das 33 preparações, 13 foram excluídas mediante critérios pré-estabelecidos. Das 20 restantes, 10 cumpriram o tempo máximo do protocolo(180 minutos). Com relação ao animal suporte houve deterioração hemodinâmica progressiva c/ queda da pressão arterial média(89,30±6,09mmHg->47,50±6,35mmHg). Com relação ao corações isolado, das 10 preparações que cumpriram os 180 minutos de protocolo, houve estabilidade hemodinâmica. As variáveis laboratoriais mostraram queda progressiva do sódio, potássio e hemoglobina, sendo compatível com hemodiluição. O exame anatomopatológico mostrou espaçamento maior entre fibras, compatível com edema. O presente modelo mostrou estabilidade e atividade de 100% das preparações em 60 minutos, havendo perdas progressivas chegando a 50% das preparações em atividade em 180 minutos. O presente modelo, dentro das limitações estabelecidas é viável para pesquisas cardiovasculares.

Heart failure due to right ventricular metastatic neuroendocrine tumor

We report a case of a female patient that was referred to our service with progressive weakness and dyspnea. Three years ago, she had been submitted to hysterectomy and salpingo-oforectomy followed by adjuvant radiotherapy due to uterine cervix neuroendocrine tumor. Two-dimensional echocardiography showed a dense sessile mass in the right ventricle causing right and left ventricular filling restriction. Despite chemotherapy the patient died and necropsy confirmed metastases from neuroendocrine tumor to the right ventricle. (C) 2007 Elsevier B.V. All rights reserved.

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.