Case management program for patients with chronic heart failure: effectiveness in terms of mortality, hospital admissions and costs.

Background: At 360 000 cases annually, heart failure is the most common main diagnosis in adults in German hospitals. Treating heart failure is expensive. This study tested whether patients in the case management program (CMP) "CorBene--Better Care for Patients With Heart Failure" have a lower mortality rate and lower hospital admission and readmission rates than patients receiving regular management.

Reduction of neointimal hyperplasia in porcine coronary arteries by 2-deoxy-D-glucose.

Background: The drug eluting stents have been shown to play a substantial role in preventing in-stent restenosis. This study was initiated to determine the efficacy of 2-deoxy-D-glucose (2-DG) in an in-stent restenosis model for reducing neointimal hyperplasia after coronary stent placement.

Methods: In a porcine overstretch model, three kinds of stents were investigated (n = 12 per group): bare metal stents (BMS), rapamycin-eluted stents (RES), and BMS after intracoronary short-term application of 2-DG (DGS).

Multiple episodes of a transient global left ventricular dysfunction reminiscent to apical ballooning.

A new cardiac syndrome with transient left ventricular dysfunction has been recently reported and is referred to as Tako-Tsubo cardiomyopathy, which is characterized by a transient akinesia of the apex and compensatory basal hyperkinesis. Today, the etiology remains unknown. We report for the first time of a patient with multiple episodes of a transient global left ventricular dysfunction which is reminiscent to apical ballooning.

Brief antecedent anoxia preserves mitochondrial function after sustained undersupply: a subcellular correlate to ischemic preconditioning?

Background: There is increasing evidence that mitochondria - owning a high degree of autonomy within the cell - might represent the target organelles of the myocardial protection afforded by ischemic preconditioning. It was the aim of the study to investigate a possible subcellular correlate to ischemic preconditioning at the mitochondrial level. In addition, we tested whether this protection depends on mitochondrial ATP-dependent potassium channels (K (ATP)) and an might involve an attenuation of mitochondrial ATP hydrolysis during sustained anoxia.

Myocardial preconditioning and remote renal preconditioning--identifying a protective factor using proteomic methods?

It is still unknown whether remote ischemic preconditioning is mediated by a humoral or a neurogenic mechanism from the preconditioning to the preconditioned tissue. The purpose of the following study was to identify a possible humoral trigger of ischemic myocardial preconditioning and remote renal preconditioning. Open chest rats were subjected to a coronary artery occlusion period of 45 min followed by 2 h of reperfusion (Control animals; n = 6).

Metabolic control analysis of the Warburg-effect in proliferating vascular smooth muscle cells.

The accumulation and proliferation of vascular smooth muscle cells (VSMC) within the vessel wall is an important pathogenic feature in the development of atherosclerosis. Glucose metabolism has been implicated to play an important role in this cellular mechanism. To further elucidate the role of glucose metabolism in atherogenesis, glycolysis and its regulation have been investigated in proliferating VSMC.

Myocardial energy metabolism in ischemic preconditioning and cardioplegia: a metabolic control analysis.

For both, cardioplegia (CP) and ischemic preconditioning (IP), increased ischemic tolerance with reduction in infarct size is well documented. These cardioprotective effects are related to a limitation of high energy phosphate (HEP) depletion. As CP and IP have to be assumed to act by different mechanisms, their effects on myocardial HEP metabolism cannot be assumed to be identical.

Human hibernating myocardium is jeopardized by apoptotic and autophagic cell death.

Objectives: The aim of the present study was to objectify the loss of myocytes and the mechanism by which myocytes die in human hibernating myocardium (HHM).

Background: Intracellular degeneration, reduced cellular protein synthesis, and the replacement fibrosis contribute to structural disintegration of HHM.

Methods: In 14 patients, HHM was diagnosed by dobutamine echocardiography, radionuclide ventriculography, and thallium-201 scintigraphy.

Increased glycolysis as protective adaptation of energy depleted, degenerating human hibernating myocardium.

In the current study on human hibernating myocardium (HHM), we tested the hypothesis that increased glycolysis might exert a positive effect during a supply-demand balance situation by augmentation of myocardial energy formation. In 14 patients HHM was preoperatively detected by clinical methods and validated by the recovery of contractile function three months following revascularization. During open-heart surgery, transmural biopsies were removed from the hibernating areas and analyzed using biochemical and morphologic methods.

Procyclic Trypanosoma brucei do not use Krebs cycle activity for energy generation.

The importance of a functional Krebs cycle for energy generation in the procyclic stage of Trypanosoma brucei was investigated under physiological conditions during logarithmic phase growth of a pleomorphic parasite strain. Wild type procyclic cells and mutants with targeted deletion of the gene coding for aconitase were derived by synchronous in vitro differentiation from wild type and mutant (Delta aco::NEO/Delta aco::HYG) bloodstream stage parasites, respectively, where aconitase is not expressed and is dispensable. No differences in intracellular levels of glycolytic and Krebs cycle intermediates were found in procyclic wild type and mutant cells, except for citrate that accumulated up to 90-fold in the mutants, confirming the absence of aconitase activity.

Activation of heterotrimeric G proteins by a high energy phosphate transfer via nucleoside diphosphate kinase (NDPK) B and Gbeta subunits. Specific activation of Gsalpha by an NDPK B.Gbetagamma complex in H10 cells.

Formation of GTP by nucleoside diphosphate kinase (NDPK) can contribute to G protein activation in vitro. To study the effect of NDPK on G protein activity in living cells, the NDPK isoforms A and B were stably expressed in H10 cells, a cell line derived from neonatal rat cardiomyocytes. Overexpression of either NDPK isoform had no effect on cellular GTP and ATP levels, basal cAMP levels, basal adenylyl cyclase activity, and the expression of G(s)alpha and G(i)alpha proteins.

Metabolic control analysis of anaerobic glycolysis in human hibernating myocardium replaces traditional concepts of flux control.

Myocardial hibernation represents an adaptation to sustained ischemia to maintain tissue vitality during severe supply-demand imbalance which is characterized by an increased glucose uptake. To elucidate this adaptive protective mechanism, the regulation of anaerobic glycolysis was investigated using human biopsies. In hibernating myocardium showing an increase in anaerobic glycolytic flux metabolizing exogenous glucose, the adjustment of flux through this pathway was analyzed by flux:metabolite co-responses.

Regulation of glycolytic flux in ischemic preconditioning. A study employing metabolic control analysis.

Exact adjustment of the Embden-Meyerhof pathway (EMP) is an important issue in ischemic preconditioning (IP) because an attenuated ischemic lactate accumulation contributes to myocardial protection. However, precise mechanisms of glycolytic flux and its regulation in IP remain to be elucidated. In open chest pigs, IP was achieved by two cycles of 10-min coronary artery occlusion and 30-min reperfusion prior to a 45-min index ischemia and 120-min reperfusion.

Lactate accumulation rather than ATP depletion predicts ischemic myocardial necrosis: implications for the development of lethal myocardial injury.

In ischemia, the myocardial metabolic status determines the expansion of necrosis. Decreased ATP levels and increased lactate contents in ischemic myocardium undergoing lethal injury are known to be related to the expansion of irreversible damage. However, their individual contributions have not yet been firmly established.

Severe energy deprivation of human hibernating myocardium as possible common pathomechanism of contractile dysfunction, structural degeneration and cell death.

Objectives: We tested the hypothesis that severe alterations in myocardial energy metabolism play an important role in the pathophysiology of human hibernating myocardium (HHM).

Background: It is well established that a disturbed myocardial energy metabolism results in impairments of contractile performance, structure and viability. All of these are important characteristics of HHM.