[Pulmonary vein isolation in atrial fibrillation using pulsed field ablation]. / Pulmonalvenenisolation bei Vorhofflimmern mittels "pulsed field ablation".

Atrial fibrillation is the most common supraventricular arrhythmia with increasing incidence and prevalence. Until now, thermal energy sources such as radiofrequency or cryoablation have been used for pulmonary vein isolation of atrial fibrillation but these have led to indiscriminate tissue destruction in the target area. Pulsed field ablation (PFA) is an energy modality that does not utilize thermal effects. An ultrarapid electric field produces irreversible changes in cell membrane pores (irreversible electroporation) culminating in cell death. The myocardium is very sensitive to PFA compared to the esophagus, the pulmonary veins or the phrenic nerve. Consequently, it is possible to perform effective ablation of the pulmonary veins in a very short time and to make the treatment time more effective without causing relevant collateral damage. The treatment offers a potential paradigm shift from catheter ablation of cardiac arrhythmia.

[Differential diagnostics of unclear syncope]. / Differenzialdiagnostik unklarer Synkopen.

The clarification of syncope is a diagnostic challenge as possible causes often occur only intermittently. Therefore, a detailed and standardized anamnesis is essential as it 1) differentiates syncope from other transient losses of consciousness (TLOC) and 2) directly clarifies possible causes of syncope. The risk stratification plays a central and very important role in order to avoid unnecessary examinations in patients with benign syncope and to provide patients with life-threatening, mostly cardiac syncopal episodes with timely diagnostics and treatment. In cases where the cause of syncope is still unclear, a standardized approach is indicated using extended diagnostics, such as a tilt table examination, a carotid sinus pressure test, prolonged telemetric monitoring or clarification with an implantable loop recorder (ILR).

Cell size distribution as a parameter for the predetermination of exponential growth during repeated batch cultivation of CHO cells.

The routine measurement of the cell size distribution of a Chinese hamster ovary (CHO) cell population during a repeated batch process enables the predetermination of exponential growth even 24 h before the population enters the log phase, due to a short but significantly increased cell size during the lag phase. A prolongation of the stationary phase causes to progressive limitation in asparagine, serine, and ethanolamine. Such extended limitation influences the duration of the following lag phase and obviously induces a synchronization of the cell population that can be monitored easily by a fast cell size analyzing technique. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 793-797, 1997.

The biochip. A new membrane bioreactor system for the cultivation of animal cells in defined tissue-like cell densities.

Based on the laminar structure of the human liver tissue, a high cell density membrane bioreactor was developed that emulates a cell layer thickness of 40 microns. The "biochip" consists of a platinum-coated metal cell grid covered with two microfiltration membranes to form separate cell chambers of defined volume. Starting with a continuous chemostat process, the viability of a model suspension cell culture could be stabilized at 98%. In a second step these cells were transferred into the biochip system and were cultivated successfully for several days under tissue-like cell densities in a modified membrane holder under cross-flow conditions.

Influence of targeted asparagine starvation on extra- and intracellular amino acid pools of cultivated Chinese hamster ovary cells.

For the development of an expression system with an amino-acid-inducible promoter, the influence of extracellular stress, by starvation of the non-essential amino acid asparagine, on the extra- and intracellular amino acid pool was investigated. Therefore a widely used nontransformed CHO cell line was cultivated in a serum-free and optimized DMEM/F12 medium in repeated batch mode. During the last repeat the medium contained no asparagine. The cells could compensate totally for this lack by an increased conversion of aspartate, glutamate, asparagine, serine, glutamine and arginine, while almost the whole intracellular pool of amino acids decreased. By this enhanced metabolic activity the maximum growth rate rose from 0.8 day-1 in complete medium to 1.1 day-1 in asparagine-free medium. The exceptional increase in asparagine biosynthesis points to a strong activation of asparagine synthetase, the key enzyme within the asparagine biosynthesis pathway. The regulation mechanism for the asparagine synthetase at the transcription level had to be analysed further in detail and will lead to an asparagine-sensitive promotor. To investigate reaction cascades that influence the protein synthesis or the overall gene expression, one had to look carefully at intracellular amino acid levels, because of their importance for polypeptide synthesis and energy supply, but also because of their obvious sensitivity to extracellular stresses.