ABSTRACT
Objective To study the effect of overwork stress response on the expression of connexin 43（Cx43） and connexin 45（Cx45） in cardiomyocytes and on cardiac function. Methods The experimental animals were divided into control group, overworked 1-month group and overworked 2-month group. A overworked rat model was established by forcing swimming of overworked group. The expressions of Cx43 and Cx45 in myocardial tissues of experimental animals were detected by Western blotting, while the corresponding myocardial tissues were stained with hematoxylin-eosin （HE） staining and Masson's staining, then histologically observed. Results Western blotting results showed that, compared with the control group, Cx43 expression in myocardial tissues of overworked rats decreased while Cx45 expression increased. HE staining and Masson's staining results showed that hypertrophy, rupture and interstitial fiber tissue hyperplasia were observed in myocardial fibers of overworked rats. Conclusion Overwork stress response may affect cardiac function as an independent factor and may even cause heart failure or arrhythmias and lead to death.
Subject(s)
Animals , Rats , Arrhythmias, Cardiac/metabolism , Connexin 43/metabolism , Connexins/metabolism , Heart Failure , Myocardium , Myocytes, Cardiac/metabolismABSTRACT
OBJECTIVES@#To observe the expression changes of hypoxia inducible factor-1α（HIF-1α） and vascular endothelial growth factor-A （VEGF-A） in rats with arrhythmias, and to explore the differences of the expression pattern in the two indicators of acute myocardial ischemia caused by arrhythmias and coronary insufficiency.@*METHODS@#The arrhythmia was induced by CaCl₂, and the expression changes of HIF-1α and VEGF-A were detected by immunohistochemistry, Western blotting and real-time PCR within 6 h after the arrhythmia in rats.@*RESULTS@#The expression of HIF-1α and VEGF-A showed diffuse in the myocardial tissue of rats died from arrhythmias. Both of them increased in the early arrhythmia, then decreased. Extensive myocardial ischemia happened at the beginning of arrhythmia occurrence and its range didn't expand with time.@*CONCLUSIONS@#The expressions of HIF-1α and VEGF-A in myocardium of the rats with arrhythmia can provide evidence for the differential diagnosis of acute myocardial ischemia caused by fatal arrhythmia and coronary insufficiency.
Subject(s)
Animals , Rats , Arrhythmias, Cardiac/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Myocardial Ischemia/metabolism , Myocardium/metabolism , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Abstract Cardiac remodeling is defined as a group of molecular, cellular and interstitial changes that manifest clinically as changes in size, mass, geometry and function of the heart after injury. The process results in poor prognosis because of its association with ventricular dysfunction and malignant arrhythmias. Here, we discuss the concepts and clinical implications of cardiac remodeling, and the pathophysiological role of different factors, including cell death, energy metabolism, oxidative stress, inflammation, collagen, contractile proteins, calcium transport, geometry and neurohormonal activation. Finally, the article describes the pharmacological treatment of cardiac remodeling, which can be divided into three different stages of strategies: consolidated, promising and potential strategies.
Resumo A remodelação cardíaca é definida como um conjunto de mudanças moleculares, celulares e intersticiais cardíacas, que se manifestam clinicamente por alterações no tamanho, massa, geometria e função do coração, em resposta à determinada agressão. Esse processo resulta em mal prognóstico, pois está associado com a progressão da disfunção ventricular e arritmias malignas. Nessa revisão, são discutidos os conceitos e as implicações clínicas da remodelação, além do papel fisiopatológico de diferentes fatores, incluindo morte celular, metabolismo energético, estresse oxidativo, inflamação, colágeno, proteínas contráteis, transporte de cálcio, geometria e ativação neurohormonal. Finalmente, o artigo apresenta o tratamento farmacológico, que pode ser dividido em três estágios: estratégias consolidadas, promissoras e potenciais.
Subject(s)
Humans , Ventricular Dysfunction/drug therapy , Ventricular Dysfunction/physiopathology , Ventricular Remodeling/physiology , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Arrhythmias, Cardiac/drug therapy , Arrhythmias, Cardiac/metabolism , Arrhythmias, Cardiac/physiopathology , Calcium/metabolism , Collagen/metabolism , Myocardial Infarction/drug therapy , Myocardial Infarction/metabolism , Myocardial Infarction/physiopathology , Oxidative Stress , Ventricular Dysfunction/metabolismABSTRACT
FUNDAMENTO: A doença de Chagas, causada pelo protozoário Trypanosoma cruzi, é uma das mais importantes causas de insuficiência cardíaca na América Latina. A terapia celular vem sendo investigada como uma possível opção terapêutica para pacientes com doenças cardiovasculares. OBJETIVO: O objetivo deste estudo foi avaliar os efeitos da terapia com células-tronco mesenquimais em um modelo experimental de cardiomiopatia chagásica crônica. MÉTODOS: Camundongos C57BL/6 foram infectados com 1000 tripomastigotas da cepa Colombiana de T. cruzi e, após seis meses de infecção, foram tratados com células-tronco mesenquimais derivadas de tecido adiposo humano (CTTAs) ou com meio DMEM (controle). O grupo tratado recebeu duas injeções intraperitoneais de CTTAs (1x106 células / dose), com um mês de intervalo entre as duas doses. Antes e após 1 e 2 meses de tratamento, os animais chagásicos e controles normais foram submetidos à eletrocardiograma e teste ergoespirométrico. Todos os animais foram sacrificados sob anestesia após 2 meses de tratamento, para análise histopatológica do coração. RESULTADOS: Não foi observada melhora de arritmias e da função cardiovascular no grupo tratado com CTTAs, porém secções de corações de camundongos deste grupo apresentaram uma redução significativa do número de células inflamatórias (p < 0,0001) e da área de fibrose (p < 0,01) em comparação com animais chagásicos tratados com DMEM. CONCLUSÃO: Deste modo, conclui-se que a administração de CTTAs por via intraperitoneal é capaz de reduzir inflamação e fibrose no coração de camundongos cronicamente infectados por T. cruzi, porém não teve efeitos na função cardíaca dois meses após o transplante.
BACKGROUND: Chagas disease, caused by the protozoan Trypanosoma cruzi, is a major cause of heart failure in Latin America. Tissue therapy has been investigated as a possible therapeutic option for patients with cardiovascular disease. OBJECTIVE: This study evaluated the effects of therapy with mesenchymal stem cells in an experimental model of chronic Chagasic cardiomyopathy. METHODS: C57BL/6 mice were infected with 1000 trypomastigotes from the Colombian strain of T. cruzi and, after six months of infection, were treated with mesenchymal human stem cells from adipose tissue (STAT) or with Dulbecco/Vogt modified Eagle's minimal essential medium - DMEM (control). The treated group received two intraperitoneal injections of STAT (1x10(6) cells/dose), with a month interval between the two doses. Before and after the first and second months of treatment, the chagasic and normal control animals underwent cardiopulmonary exercise testing and electrocardiography. All animals were sacrificed under anesthesia after two months of treatment for histopathological analysis of the heart. RESULTS: No improvement was observed in arrhythmias and cardiovascular function in the group of animals treated with STAT; however, sections of mice hearts in this group revealed a significant reduction in the number of inflammatory cells (p<0.0001) and areas of fibrosis (p<0.01) in comparison with chagasic animals treated with DMEM. CONCLUSION: Thus, it is concluded that administration of intraperitoneal STAT can reduce inflammation and fibrosis in the heart of mice chronically infected with T. cruzi; however, there were no effects on the cardiac function two months after transplantation.
Subject(s)
Animals , Mice , Adipose Tissue/cytology , Chagas Cardiomyopathy/surgery , Mesenchymal Stem Cell Transplantation , Trypanosoma cruzi , Analysis of Variance , Arrhythmias, Cardiac/metabolism , Chagas Cardiomyopathy/pathology , Chagas Cardiomyopathy/physiopathology , Disease Models, Animal , Fibrosis , Injections, Intraperitoneal , Inflammation/metabolism , Physical Conditioning, Animal/methods , Random AllocationABSTRACT
Natriuretic peptides (NPs) have been found to be useful markers in differentiating acute dyspneic patients presenting to the emergency department (ED) and emerged as potent prognostic markers for patients with congestive heart failure (CHF). The best-established and widely used clinical application of BNP and NT-proBNP testing is for the emergent diagnosis of CHF in patients presenting with acute dyspnea. Nevertheless, elevated NPs levels can be found in many circumstances involving left ventricular (LV) dysfunction or hypertrophy; right ventricular (RV) dysfunction secondary to pulmonary diseases; cardiac inflammatory or infectious diseases; endocrinology diseases and high output status without decreased LV ejection fraction. Even in the absence of significant clinical evidence of volume overload or LV dysfunction, markedly elevated NP levels can be found in patients with multiple comorbidities with a certain degree of prognostic value. Potential clinical applications of NPs are expanded accompanied by emerging reports regarding screening the presence of secondary cardiac dysfunction; monitoring the therapeutic responses, risk stratifications and providing prognostic values in many settings. Clinicians need to have expanded knowledge regarding the interpretation of elevated NPs levels and potential clinical applications of NPs. Clinicians should recognize that currently the only reasonable application for routine practice is limited to differentiation of acute dyspnea, rule-out-diagnostic-tests, monitoring of therapeutic responses and prognosis of acute or decompensated CHF. The rationales as well the potential applications of NPs in these settings are discussed in this review article.
Subject(s)
Humans , Acute Coronary Syndrome/metabolism , Arrhythmias, Cardiac/metabolism , Heart Failure/metabolism , Hypertension, Pulmonary/metabolism , Natriuretic Peptides/metabolism , Sepsis/metabolismABSTRACT
An improved, simple and sensitive micromethod based on HPLC-fluorescence is described for quantification of propranolol in plasma. Only 200µL of biological sample were required. The drug and its internal standard (verapamil) are eluted after 3.6 and 8.5 min, respectively, from a 4-micron `C IND. 18ï reverse-phase column using a mobile phase consisting of 0.38 M acetate buffer, pH 5.0 and acetonitrile (65:35, v/v, isocratically) with detection at `lâmbda IND. exï- 290 nm and `lâmbda IND. emï - 358 nm. This method, validated on basis of parameters evaluated for the confidence limits of propranolol measurements in spiked blank plasma, presented 1 ng/mL sensitivity, 1-1000 ng/mL linearity, 6.2 per cent and 7.6 per cent for intra- and inter-assay precision respectively, good accuracy and high selectivity...
Subject(s)
Humans , Angina Pectoris/metabolism , Arrhythmias, Cardiac/metabolism , Extracorporeal Circulation , Hypertension/metabolism , Propranolol/pharmacokinetics , Thoracic Surgery , Chromatography, High Pressure Liquid/methods , Fluorescence , Postoperative PeriodABSTRACT
Evaluar la capacidad predictiva de la medición de la dispersión del QTc de presentar arritmias post-infarto del miocardio (IM). Estudio restrospectivo, descriptivo con comparaciones intragrupales de una muestrta de 28 pacientes, edad promedio de 53,33, cuya muestra fue tomada desde enero a septiembre de 1998, con dignóstico de IM según criterios de la New York Heart Associatio, realizándose seguimientos a todos los pacientes durante los 4 primeros días posterior a su ingreso, un total de 8 EKG por paciente midiéndose el intervalo QT en todas las derivaciones de cada EKG, QTc según, fórmula de Bazett y dispersión del mismo, la cual se obtuvo restando al máximo valor del Qtc menos el mínimo. Se compararon estos resultados con los obtenidos del Holter, estableciendo por los métodos estadísticos análisis de varianza y T de Student pareada, que para el cuarto día de estudio hubo diferencia estadísticamente significativa entre los grupos comparados en cuanto al comportamiento de su dispersión. El mantenerse disperso aún en el cuarto día de estudio pudiera relacionarse con riesgo de arritmia post IM
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Arrhythmias, Cardiac/complications , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/metabolism , Infarction/mortality , Infarction/prevention & control , Myocardial InfarctionABSTRACT
Se estudió la estabilidad de tabletas de liberación prolongada confeccionadas a partir de polimetacrilato de quinidina, mediante el control periódico de las características físicas químicas y los perfiles de liberación de la sustancia biológicamente activa en muestras envejecidas por diferentes métodos. Los resultados obtenidos demuestran que el producto analizado mantiene una estabilidad adecuada en condiciones normales de almacenamiento
Subject(s)
Drug Stability , Methylmethacrylates/pharmacokinetics , Chemistry, Pharmaceutical/methods , Quinidine/pharmacokinetics , Tablets , Arrhythmias, Cardiac/metabolismABSTRACT
Since cassava (Manihot esculenta Crantz) is a staple food item of several million people in the tropics, its toxicity cannot be underestimated. Therefore an attempt has been made to understand the metabolic changes caused by the chronic administration of sublethal doses linamarin, the principal cyanoglucoside of cassava, to rabbits. A significant rise in lactic acid and total cholesterol in liver and brain and a highly significant depletion of phospholipids of brain tissue was observed. There were also significant variations in the lactate dehydrogenase isoenzyme pattern of treated animals as compared with the control rabbits. The findings suggest that some of the biological effects of linamarin are similar to those of free cyanide.