Dominant-negative suppression of HCN channels markedly reduces the native pacemaker current I(f) and undermines spontaneous beating of neonatal cardiomyocytes.

Background: The pacemaker current I(f) contributes to spontaneous diastolic depolarization of cardiac autonomic cells. In heterologous expression, HCN channels exhibit a hyperpolarization-activated inward current similar to I(f). However, the links between HCN genes and native I(f) are largely inferential, and it remains unknown whether I(f) is essential for cardiac pacing.

Ca2+-handling in heart failure--a review focusing on Ca2+ sparks.

[Ca2+]i-transients have been shown to be altered in isolated ventricular myocytes from terminally failing human myocardium. It has been demonstrated that one reason for this alteration is a reduction in the Ca2+ content of the sarcoplasmic reticulum (SR). Further investigations were done to investigate, whether there may be an additional defect of the Ca2+-release mechanisms from the SR.

[Hormonal hyperactivity in heart failure. Differences in beta blockers].

Pathophysiology: Heart failure is characterized by a disturbed contractility and activation of neurohumoral mechanisms. Activation of the adrenergic system and the beta-adrenergic signal transduction pathway leads to downregulation of beta 1-receptors of the heart muscle cell membrane.

Therapy: In addition to ACE inhibitors, diuretics and glycosides, beta blockers are an integral part in the combination therapy of patients with heart failure.

Identification of gating modes in single native Na+ channels from human atrium and ventricle.

The aim of the present study was to investigate the single-channel properties of different gating modes in the native human cardiac Na+ channel. Patch-clamp experiments were performed at low noise using ultrathick-walled pipettes. In 17 cell-attached patches containing only one channel, fast back and forth switching between five different Na+-channel gating modes (F-mode, M1-mode, M2-mode, S-mode, and P-mode) was identified, but no difference in the gating properties was found between normal and diseased cardiomyocytes from atrium or ventricle, respectively.

[Development of ultrasonography in a radiological university department from 1994 to 2001].

Background: In 1994, 5 % of a total of 25 718 examinations and 7 % of all 4630 B-mode sonograms performed in the Radiology Department, University of Cologne was classified as not indicated. In light of these results, the health care policy guidelines for sonographic indications have been amended.

Purpose: The aim of this study was to establish the current rate of non-indicated sonographic examinations performed in routine diagnostics by radiology departments at university hospitals, to determine the reasons for such over-diagnosis and identify which regulatory mechanisms can be implemented to prevent his.

Calcium sparks in human ventricular cardiomyocytes from patients with terminal heart failure.

Cardiomyocytes from terminally failing hearts display significant abnormalities in e-c-coupling, contractility and intracellular Ca(2+) handling. This study is the first to demonstrate the influence of end-stage heart failure on specific properties of Ca(2+) sparks in human ventricular cardiomyocytes. We investigated the frequency and characteristics of spontaneously arising Ca(2+) sparks in single isolated human myocytes from terminally failing (HF) and non-failing (NF) control myocardium by using the Ca(2+) indicator Fluo-3.

Role of the cardiac Na(+)/H(+)exchanger in [Ca(2+)](i)and [Na(+)](i)handling during intracellular acidosis. Effect of cariporide (Hoe 642).

Intracellular acidosis is one of the alterations occurring in cardiac ischemia and has been discussed to be important in altering excitation--contraction coupling. The aim of this study was to determine how intracellular acidosis may affect intracellular sodium and calcium handling. Cardiomyocytes were isolated from the hearts of adult male guinea-pigs by standard techniques and superfused with modified Tyrode's solution at room temperature, either HEPES buffered containing 10 mM NaHCO(3)or HEPES buffered without NaHCO(3), in order to examine a possible interaction with the sodium bicarbonate symport.

Identification of the cardiac ryanodine receptor channel in membrane blebs of sarcoplasmic reticulum.

Blebs of the sarcoplasmic reticulum (SR) membrane of heart muscle cells were generated after saponin perforation of the plasma membrane followed by complete hypercontraction of the cell. Although characteristic proteins of the plasma membrane, namely the beta1-adrenoreceptor and Galphai, were stained by monoclonal antibodies in the hypercontracted cells, these proteins could not be detected in the adjacent blebs. Monoclonal antibodies to the cardiac ryanodine receptor (RyR2), calsequestrin and SERCA2 bound at different amounts to surface components of the blebs and to components of the hypercontracted cells.

[Transcatheter closure of atrial septal defects in adults. Practicality and safety of four different closure systems used in 102 patients].

Background And Objective: Surgical closure of secundum atrial septal defect (ASD) or patent foramen ovale (PFO) is a procedure with few complications. But this surgical intervention can nowadays be avoided by transcatheter insertion of occluding devices. Such interventional methods must be judged against the results of surgical procedures.

The ultrarapid and the transient outward K(+) current in human atrial fibrillation. Their possible role in postoperative atrial fibrillation.

Atrial fibrillation (AF) causes distinct changes in atrial conduction, characterized as electrical remodeling. Experimental data on the possible significance of alterations of specific K(+)outward currents in this process are still limited in human AF. The ultra-rapid delayed rectifier current (I(Kur)) has not been studied in AF with respect to its sensitivity to 4-Aminopyridine (4-AP).

Congenital dyserythropoietic anemia type III associated with congenital atrioseptal defect has led to severe cardiac problems in a 32-year-old patient.

We report the case of a 32-year-old woman who was admitted at hospital because of ortho-dyspnea, arrhythmia, and paleness. Clinical examination showed continuous arrhythmia, systolic heart murmur, enlargement of spleen and liver, and pathologic hematological parameters, thus indicating an intravasal hemolysis (elevated HBDH, bilirubin, and reticulocytes; reduced hemoglobin and haptoglobin levels), and bone-marrow-smears showed a typical cytomorphology of CDA III. The patient's diagnosis was heart failure caused by mitral valve insufficiency due to congenital atrioseptal defect associated with congenital dyserythropoietic anemia type III (CDA III).

Characterization of a [Ca2+]i-dependent current in human atrial and ventricular cardiomyocytes in the absence of Na+ and K+.

Objectives: In situations of [Ca2+]i-overload, arrhythmias are believed to be triggered by delayed afterdepolarizations, which are generated by a transient inward current ITI. This study was designed to examine [Ca2+]i-dependent membrane currents in the absence of the Na+/Ca(2+)-exchanger as possible contributors to ITI in human cardiac cells.

Methods: The whole cell voltage clamp technique was used for electrophysiological measurements in human atrial and ventricular cardiomyocytes.

Modulation of the hyperpolarization-activated inward current (If) by antiarrhythmic agents in isolated human atrial myocytes.

The hyperpolarization-activated inward current (If) has been discussed to contribute to arrhythmias in human atrial myocardium. If was found to be increased by beta-adrenergic stimulation. In the present study, we evaluate the modulation of If by carbachol, adenosine and by class Ic, III and IV antiarrhythmic drugs in isolated human atrial myocytes.

Cell swelling causes the action potential duration to shorten in guinea-pig ventricular myocytes by activating IKATP.

In guinea-pig ventricular myocytes, cell swelling by incubation in hypotonic solution caused a pronounced shortening of the action potential duration (APD90: 15.5+/-14.6% compared to control; mean +/- SD) after a latency of 12 min when the intracellular ATP concentration was 2 mM.

Molecular basis of transient outward potassium current downregulation in human heart failure: a decrease in Kv4.3 mRNA correlates with a reduction in current density.

Background: Despite advances in medical therapy, congestive heart failure remains a major cause of death in the developed world. A disproportionate number of the deaths of patients with heart failure are sudden and presumed to be arrhythmic. Heart failure in humans and in animal models is associated with prolongation of the action potential duration (APD), the result of downregulation of K+ currents-prominently, the Ca2+-independent transient outward current (Ito).

Characterization of the hyperpolarization-activated inward current in isolated human atrial myocytes.

Objective: The hyperpolarization-activated inward current (I(f)) has been discussed to contribute to arrhythmias in rat hypertrophied and human failing ventricular myocardium. Cat atrial myocytes were found to exhibit variable size of I(f). In the present study, we evaluate characteristics of I(f) in human atrial myocardium and investigate if human atria might exhibit any electrophysiological heterogeneity in the diastolic voltage range.

Increased availability and open probability of single L-type calcium channels from failing compared with nonfailing human ventricle.

Background: The role of the L-type calcium channel in human heart failure is unclear, on the basis of previous whole-cell recordings.

Methods And Results: We investigated the properties of L-type calcium channels in left ventricular myocytes isolated from nonfailing donor hearts (n= 16 cells) or failing hearts of transplant recipients with dilated (n=9) or ischemic (n=7) cardiomyopathy. The single-channel recording technique was used (70 mmol/L Ba2+).

Simulation study of cellular electric properties in heart failure.

Patients with severe heart failure are at high risk of sudden cardiac death. In the majority of these patients, sudden cardiac death is thought to be due to ventricular tachyarrhythmias. Alterations of the electric properties of single myocytes in heart failure may favor the occurrence of ventricular arrhythmias in these patients by inducing early or delayed afterdepolarizations.

Calcium content of the sarcoplasmic reticulum in isolated ventricular myocytes from patients with terminal heart failure.

Systolic [Ca2+]i-transients have been shown to be depressed in isolated ventricular myocytes from patients with terminal heart failure compared to controls. Experiments were performed in human ventricular cells to investigate whether this reduced systolic [Ca2+]i-transient may be due to a decreased Ca(2+)-content of the sarcoplasmic reticulum (SR). Single myocytes were isolated from left ventricular myocardium of patients with terminal heart failure undergoing cardiac transplantation.

Hyperpolarization-activated inward current in ventricular myocytes from normal and failing human hearts.

Background: The hyperpolarization-activated inward current (I[f]) was found to be overexpressed in hypertrophied rat ventricular myocytes, indicating that I(f) might favor arrhythmias in hypertrophied or failing ventricular myocardium. In the present study, we evaluated whether I(f) is expressed in human ventricular myocardium, if it may be increased in human heart failure, and if its autonomic modulation may be altered.

Methods And Results: The whole-cell patch-clamp technique was used to record I(f) in isolated ventricular myocytes from 34 failing (dilated [DCM] or ischemic [ICM] cardiomyopathy) and 13 donor hearts (NF).