For several years, the standard implantation strategy of ventricular assist devices has involved a full sternotomy approach. However, less invasive implantation techniques are now becoming increasingly popular as they are associated with reduction of trauma, blood loss, and arrhythmogenic complications, as well as a decreased duration of intensive care unit and in-hospital stay. Thus, due to miniaturization and increasing technical improvement of ventricular assist devices, less invasive strategies for implantation, explantation, exchange, and concomitant cardiac procedures are on the rise.In this review article, we report on the state of the art of less invasive techniques for implantation, explantation, exchange, and combined cardiac procedures of ventricular assist devices.

There are now numerous in vitro and in silico ADME alternatives to in vivo assays but how do different industries incorporate them into their decision tree approaches for risk assessment, bearing in mind that the chemicals tested are intended for widely varying purposes? The extent of the use of animal tests is mainly driven by regulations or by the lack of a suitable in vitro model. Therefore, what considerations are needed for alternative models and how can they be improved so that they can be used as part of the risk assessment process? To address these issues, the European Partnership for Alternative Approaches to Animal Testing (EPAA) working group on prioritisation, promotion and implementation of the 3Rs research held a workshop in November, 2008 in Duesseldorf, Germany. Participants included different industry sectors such as pharmaceuticals, cosmetics, industrial- and agro-chemicals. This report describes the outcome of the discussions and recommendations (a) to reduce the number of animals used for determining the ADME properties of chemicals and (b) for considerations and actions regarding in vitro and in silico assays. These included: standardisation and promotion of in vitro assays so that they may become accepted by regulators; increased availability of industry in vivo kinetic data for a central database to increase the power of in silico predictions; expansion of the applicability domains of in vitro and in silico tools (which are not necessarily more applicable or even exclusive to one particular sector) and continued collaborations between regulators, academia and industry. A recommended immediate course of action was to establish an expert panel of users, developers and regulators to define the testing scope of models for different chemical classes. It was agreed by all participants that improvement and harmonization of alternative approaches is needed for all sectors and this will most effectively be achieved by stakeholders from different sectors sharing data.

The Bhas-system was established by using the reference carcinogen 3-methylcholanthrene as an initiator and TPA and Insulin as promoters. Increasing concentrations led to a dose-dependent increase in transformed foci. By selective trypsinization separate cultures could be established from foci cells and from normal cells. Micronucleus frequencies turned out to be 1.7 fold higher in cultures of transformed cells. More surprisingly, no significant differences in mitotic rates and cell cycle distribution between cultures of transformed and normal cells exist. Nevertheless, parallel staining of microfilaments and nuclei clearly displayed a dense and multilayered piling-up of cells in foci. Thus alterations in adhesion protein profiles and enzyme activities modulating cellular adhesion and migration seem to be involved in the process of focus formation. These may be promising candidates for the identification of molecular markers leading to a more objective scoring of foci and a greater acceptance of cell transformation tests in general.