Cardiac and electrophysiological effects of primary and refined extracts from Leonurus cardiaca L. (Ph.Eur.).

Although several antiarrhythmic drugs of chemical origin are in clinical use since decades, their application is often limited by their adverse effects and especially by their inherited proarrhythmic risk, which can lead to a significantly increased mortality in patients receiving these compounds. On the other hand, aqueous extracts from the aerial parts of the European Lamiaceae Leonurus cardiaca (Ph.Eur.) have been used for centuries as a remedy against tachyarrhythmia and other cardiac disorders. Nevertheless, a scientific basis for the claim of direct cardiac electrophysiological, antiarrhythmic, or functional effects of Leonurus cardiacae herba (LCH) preparations has not been established until now. In order to enrich the active constituents from the primary extract which was tested as the most cardioactive, namely the aqueous Soxhlet extract, and to eliminate undesired substances such as the dichloromethanic fraction or potassium, a bioassay guided fractionation procedure was applied, resulting in the development of a Leonurus cardiaca refined extract (LCRE) which was characterised together with Leonurus crude extracts by a newly developed gradient elution HPLC fingerprint analysis for separation and quantification of six major phenolics as well as by qNMR for determining the stachydrine content. This refined extract was applied intracoronarily in isolated rabbit hearts perfused according to the Langendorff technique. Mapping experiments with 256 electrodes on the heart surface showed a reduction of left ventricular pressure and an increase of relative coronary flow at concentrations of 1.0 and 2.0 mg/mL LCRE. Furthermore, the PQ-interval was prolonged and both the basic cycle length and the activation recovery interval increased. In addition, voltage-clamp measurements were performed on the following cell models in order to characterise the electrophysiological profile of LCRE: neonatal rat ventricular cardiomyocytes to investigate the effect on I(Na) and I(Ca.L), sinoatrial node cells and ventricular myocytes isolated from adult guinea pigs to test effects on I(f) and action potential (AP) duration, as well as HERG-transfected HEK 293 cells to analyse the influence on the I (K.r). In these voltage clamp experiments LCRE exerted a calcium-antagonistic activity by I(Ca.L) blockade, reduced the repolarising current I(K.r), and prolonged the AP-duration, while I(Na) was not affected. Although LCRE displayed only weak effects on the I(f) amplitude and voltage dependence, it significantly prolonged the activation time constant of I(f). Thus, LCRE acts on multiple electrophysiological targets, specifically I(Ca.L), I(K.r), and I(f), observed both at whole organ and single cell level.

[Optimising MR image quality of the canine nose]. / Optimierung der Bildqualität bei der MR-Darstellung der Hundenase.

The aim of this study was to optimize magnetic resonance imaging (MRI) sequences, which are already used for examinations of dog noses, to show more detail of the fine structures of the nose. Examinations were first carried out on phantoms. The resulting improved sequence parameters were further optimized on five clinically healthy animals. Images were made using nine optimized sequences on another five clinically healthy dogs, and the image quality was evaluated by three reviewers. Detail recognition and contour sharpness of the conchae and turbinates in the peripheral and central regions were evaluated as were image noise, contrast, subjective image quality, and diagnostic value. The best evaluation was given to a spin echo sequence. Second place went to a turbo spin echo sequence. Both sequences were proton density-weighted. The gradient echo sequences received the poorest evaluation and proved to be unsuitable for the anatomic portrayal of the nose. The TSE-sequence is more suitable to the clinical routine because of the significant shorter measure time compared to the SE-sequence. In case of suspected pathologic changes, a T2-weighted image sequence must also always be acquired, despite it being inappropriate to illustrate anatomic details.