The mechanism of RNA oxidation involved in the development of heart failure

Heart failure (HF) has become a global public health problem due to its unclear pathogenesis. Our previous studies have found that RNA oxidation is associated with the occurrence and development of a variety of chronic diseases in the elderly, but whether RNA oxidation is related to the pathogenesis of HF remains unclear. Male Dahl salt-sensitive rats (DSSR) were divided into 8% NaCl groups and 0.3% NaCl groups. The blood pressure of DSSR, HE staining of cardiac tissue, cardiac function index of colour Doppler echocardiography and plasma N-terminal probrain Natriuretic Peptide (NT-ProBNP) were used to evaluate the model making. The levels of 8-hydroxyguanosine (8-oxoGsn) and 8-hydroxydeoxyguanosine (8-oxodGsn) in myocardium and urine of DSSR were determined by high-performance liquid chromatography–mass spectrometry (LC-MS/MS). The expression of ERK-MAPK pathway and MTH1 was detected by Western blot (WB). Rats in the 8% NaCl group developed heart failure symptoms such as increased blood pressure, myocardial hypertrophy, decreased diastolic function, and increased plasma NT-ProBNP. The content of 8-oxoGsn in urine and heart tissue also increased, which was positively correlated with the related indicators of heart failure. This process is also accompanied by the sequential activation of ERK-MAPK pathway molecules and the increase of MTH1. The mechanism of RNA oxidation and inhibition is related to the occurrence and development of HF, which may be involved through ERK-MAPK pathway.     

Changes in adrenergic receptors during the development of heart failure

Moderate and severe stages of congestive heart failure due to the loss of myocardium upon coronary occlusion in rats was associated with an increase in alpha-adrenergic receptors and a decrease in beta-adrenergic receptors in the viable left ventricle. However, at early stages of heart failure the number of beta-adrenergic receptors was decreased without any changes in the number of alpha-adrenergic receptors. The affinities of these receptors to alpha receptor antagonist (³H-prazosin) and beta receptor antagonist (³H-dihydroalprenolol) were not altered in the failing hearts. On the other hand, the pattern of changes in both alpha- and beta-adrenergic receptors in heart membranes treated with oxygen free radical generating system was different from that seen in the failing hearts. In particular, the affinities for these receptors were decreased whereas the number of beta-receptors was increased and the number of alpha-receptors was decreased or unchanged. These results indicate that alterations in the adrenergic receptors in heart failure are not due to the formation of oxygen free radicals.     

End-stage heart failure and mechanical circulatory support: feasibility of discharge from hospital

Background. Due to the shortage of donor hearts, mechanical circulatory support is increasingly being used as a bridge to transplantation. In order to allow for more widespread use of ventricular assist devices it is mandatory that patients are not continuously hospitalised. We present the results of our experience with patients with end-stage heart failure, discharged from hospital after implantation of a ventricular assist device and followed in an outpatient setting. Methods. After an intensive training and education programme, focusing on the management of the percutaneous driveline and instructions on how to handle in case of an alarm or malfunction of the device, patients were discharged. They were followed in the outpatient department. All regular and unplanned visits were registered, including readmissions. Results. Twenty-seven patients treated with a ventricular assist device were discharged from hospital. There were 37 extra visits, of these, 27 were device related resulting in 21 readmissions (0.78/patient). We treated eight infectious episodes in four patients, all device related. Furthermore seven thromboembolic episodes occurred in four patients. One patient died because of multiorgan failure seven weeks after he was readmitted with an urosepsis. In our experience of 11.4 patient years at home while on the device, only 5% of the time was spent in hospital for complications. In comparison with patients on an assist device who stayed in hospital until transplantation, there were no more complications. Conclusion. This study demonstrates that patients with end-stage heart failure, treated with a ventricular assist device, can be safely discharged from hospital, with an acceptable rate of readmissions. It results in a fair quality of life, with a high degree of independence of the patient. (Neth Heart J 2007; 15:45-50.)     

The role of anti-beta1-adrenergic receptor autoantibodies in development of heart failure

Epitopic analysis of anti-beta1-adrenergic receptor autoantibodies in the serum of patients with cardiomyopathy was performed. An immunoenzyme test system for detection of autoantibodies was developed using peptide containing 26 amino acids of the second extracellular loop of the beta1-adrenergic receptor as antigen. It was demonstrated that removal of autoantibodies against beta1-adrenergic receptor in patients with cardiomyopathy by immunoadsorption and plasmapheresis metodes led to improvement of the heart pumping capacity.     

The development of the human lymph node

Summary Lymph nodes of human fetuses from the 11th to the 20th gestational week (g.w.) were investigated by light- and electron microscopy under particular consideration of the development of the T-cell and the B-cell regions and their specific reticulum cells. Lymph node development begins as a mesenchymal condensation, containing capillaries and mesenchymal cells; this primordium bulges into a lymph sac. Within the primordium of the lymph node granulopoiesis and erythropoiesis occur temporarily from the 12th to the 14th g.w. The first lymphoid cells and undifferentiated blast cells are seen in the 12th g.w.; monocytes and macrophages can be found from the 13th g.w. onward.The development of the T-cell regions begins during the 13th g.w., before differentiation into cortex and medulla becomes obvious in the 14th g.w. Near the marginal sinus, cells displaying features of interdigitating reticulum cells (IDC) show similarities to monocytes. The morphological differentiation of the IDC is complete in the 17th g.w. when they are found in the paracortical region. Among the IDC, lymphoid cells with features of thymocytes are arranged in small groups.The first indication of the development of B-cell regions can be recognized in the 14th g.w. when precursors of dendritic reticulum cells (DRC) are seen near the marginal sinus; this area also displays lymphoblasts, immunoblasts, and plasmoblasts. During the 20th g.w. small primary follicles are discernible in the outer cortex; in addition to blast cells they contain small lymphocytes, none of which show features of thymocytes. The morphological development of DRCs is not entirely complete until the 20th g.w.; however, some cells already show a characteristic network of interwoven processes.The probable origin of (i) the IDC from monocytes, and (ii) the DRC and fibroblastic reticulum cells from a common type of mesenchymal precursor cells, as well as their significance for a specific micromilieu in the T-cell and the B-cell regions, are discussed.This investigation was supported by grants from the Deutsche Forschungsgemeinschaft and the Sonderforschungsbereich 111 of the Deutsche ForschungsgemeinschaftThe authors appreciate the contribution of human fetal material from Dr. J. von Hollweg and Dr. J. Körner, Hospital Heidberg, Hamburg, and the excellent technical assistance of Mrs. O.M. Bracker, Mrs. H. Hansen, Mrs. R. Köpke, Mrs. I. Knauer, Mrs. F. Müller, Mrs. H. Siebke, and Mrs. H. Waluk     

Myocardial heat shock proteins during the development of heart failure

When cardiomyocytes are exposed to stresses, production of heat shock proteins (HSPs) in the cells is enhanced. Such increase in cellular HSP production is considered to bring about tolerance against stress-induced cell damage. The exact role of the cellular HSPs remains unclear. In the present study, HSPs in the viable left ventricular myocardium were determined during the development of heart failure following coronary artery ligation (CAL). The rats after CAL showed symptoms of chronic heart failure (CHF) at the 8th week, but not at the 1st and 2nd weeks. Myocardial HSP27, which may bind to cytoskeletal protein, at the 1st, 2nd, and 8th weeks after CAL was approximately 180, 160, and 125% of the control, respectively. Myocardial HSP60, one of mitochondrial proteins, at the 8th week increased to 140% of the control, whereas those at the 1st and 2nd weeks did not change. Myocardial HSP72, an inducible form of HSP70 family, at the 1st week after CAL increased to 180% of the control, whereas that at the 2nd or 8th week was similar to control. Myocardial heat shock constitutive protein 73 (HSC73), a constitutively expressed form of HSP70 family, and HSP90, which may bind to steroid hormone receptor and actin fiber, of CAL rats did not alter throughout the experiment. These findings show that diverse changes in the production of myocardial HSPs occur during the development of heart failure. Only the increase in myocardial HSP60 production was associated with the development of CHF.     

The development of heart failure during transvalvular catheterization of the left ventricle in spontaneously hypertensive rats

Systemic hemodynamic parameters in 5-month-old and 10-month-old normotensive Wistar-Kyoto and spontaneously hypertensive (SHR) conscious rats were studied with microsphere technique. Cardiac index was similar in both strains of rats and was not significantly different between 5 and 10 months. Left ventricle catheter implantation through the right common carotid artery evoked the development of heart failure in 10-month-old SHR (in the first day after operation). This model can be used for screening of new drugs for heart failure treatment.     

The caudal heart of fish: not a lymph heart

The caudal heart is traditionally regarded as part of the lymphatic vessel system in fish. Recently, however, a secondary blood vessel system has been demonstrated in this class of vertebrates, while the existence of lymphatics was questioned. In corrosion cats of the secondary system it is shown that the caudal heart functions as a venous pump in the secondary circulation. Contrary to current views fish do not have true lymphatic vessels. Theories on the phylogeny of lymphatics therefore should be revised accordingly.