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The resulting change in trans-retinal ternatively, also a whole embryonic heart can be kept on an MEA voltage is measured as the ERG. For an overview on struc- for a couple of days. Spontaneous contractions are observed in all ture and function of the retina, and the basis of the ERG conditions see ref. The ERG has a multiphasic waveform. Its shape mainly the ventricular field potential Fig. The effective ranges of Quinidine, adaptation, and the species.
The full-field ERG of a dark- Sotanol, and E on the ventricular field potential du- adapted retina in response to a bright flash of white light ration are shown in Fig. Under pathophysiological conditions the shape and amplitude of these components is altered and can be influenced by pharmacological compounds. Multisite electroretinogram of explanted retinas A retina sensor, based on multisite recording of local ERGs in vitro, has been developed to easily and effectively The retina is a peripheral, easily accessible part of the cen- assess effects of pharmacological compounds and puta- tral nervous system.
Stimulation by light results in a com- tive therapeutica, drug side effects, and consequences of plex signaling by neurons within the layers of the retina degeneration-related processes on retinal signaling. The retinal ganglion cells transmit retinal in- For the recording of light-evoked activity, a retinal seg- formation to higher visual centers in the brain via their ax- ment with the pigment epithelium, dissected from an ex- ons that form the optic nerve.
Retinal function can be af- planted chicken retina, is placed ganglion cell site down fected by acute injuries, intoxications or retinal diseases, on a MEA Fig.
In clinical practice the so-called electroretinogram ERG The prominent components of the microERG can be phar- is a widely used ocular electrophysiological test to diag- macologicaly identified as shown in Fig. A a typical field po- tential of ventricular myocytes under control conditions.
The under-lying ionic conductances are indicated. Repolarization is mainly caused by potassium channels, of the IKR type. B In- fluence of various Quinidine concentrations on the ventricu- lar field potential of ventricular myocytes. D Distortion in rhythm of ventricular field potential by Quinidine.
A An explanted retina is placed assess potential drug side effects, or to screen for the ef- onto an MEA with the ganglion cell side RPE retinal pigment ep- fect of newly developed compounds. The light stimulus is projected through the transparent MEA and an MEA brain sensor application, an organotypic co-cul- retina onto the photoreceptors.
Ganglion cell activity and retinal ture model is described in the following reflecting the per- field potentials microERG are recorded by 60 substrate-inte- forant pathway projection into the hippocampus.
Kardiologie aus der Praxis - Basics
B View through an MEA on a retinal able to study processes of neurite outgrowth, synaptogen- segment white arrow from a chicken retina. The broken line esis, and regeneration. C microERG with a-, b-, c-, and d-wave of a chicken retina, evoked by full-field white Promoting repair and re-growth of neurons is an in- light, impulse duration ms, 0.
Gray curve single sweep, creasingly attractive approach to the treatment of neuronal 0. Black line 5 sweeps averaged, filtered 0.
Evaluation of treatments that may lead to neural off-line filtering at Hz—2. E Drug action on a light-evoked microERG. Light pulses ms, 0. The functionality and speci- ficity of the newly formed connections was shown by elec- trical stimulation and parallel recording of correlated ac- which is smaller in recordings from isolated retinas than tivity in the target tissue Fig. The components of evoked in recordings from intact eyes.
During superfusion with signals in the DG can be isolated pharmacologically Fig. In order to monitor long- The approach was found to be a valid in vitro model term drug effects, we currently are establishing an organo- for regeneration of the perforant pathway and a useful tool typic culture of a mammalian retina mouse, rat.
Such a system in principle consists of three main components: The sources of the recorded signals are compartments of single cells, for example, dendrites or axon hillocks. Due to local alteration of ion channel conductance, they pro- duce an extracellular field potential with a time course that is approximately equal to the transmembrane current of the active cellular compartments. For fast events, the transmembrane current and there- fore the extracellular recording is roughly equal to the first derivative of the transmembrane potential .
This can be easily illustrated by recordings from single cells con- tacting a planar electrode as outlined in Fig. The princi- ple of generation, extracellular spread, and recording of single-cell signals also holds for signals arising from sources in tissue slices.
The MEA recording then may ex- hibit slow field potentials and fast spikes arising from ac- tion potentials. Differences in amplitude and shape of the recordings from single cells and tissue slices may occur due to the distance between source and electrode and due to the mechanisms of the coupling between membrane and electrode in single-cell contacts as shown in Fig.
The passive spread of cellular signals in tissue slices has been investigated by Egert et al. This is in agreement with theoretical and numerical calculations of idealized geometries . By summation of the simultaneous activity of a larger population of cells in a tissue slice, a continuous potential field is generated.
Its spatial modulation reflects the dis- Fig.
Di- sources. Recently, Fromherz published a model to describe viding line between EC and DG, stimulation electrodes asterisks the two-dimensional profile of field potentials in brain and exemplary recording electrodes in EC and DG rings are slices . It adapts the fully fledged volume conductor marked. Correlated sig- theory used for current—source density analysis in three- nals in the DG suggest a functional connection between EC and dimensional tissue to the quite different boundary condi- DG.
Besl and Fromherz showed that this Electrical stimulation in the EC stim 1 resulted in correlated ac- model can be used to calculate the current—source density tivity in both the EC and DG, whereas stimulation in the DG stim 2 only resulted in DG activity. This unidirectional propagation is in in the CA1 region of organotypic slices from rat hippo- agreement with the perforant pathway projection in vivo campus based on recordings obtained with a FET field- effect transistor array with sensor spacing of a few mi- crometers .
In Fig. These influences should be kept in mind when the recordings of field po- Formation, spread, and recording of field potentials tentials are interpreted. Despite the widespread use of MEAs, no complete the- With MEAs extracellular potentials of cellular sources are oretical descriptions of the interfacing of cells and tissue recorded at the two-dimensional surface of a conductive with planar metallic electrodes are available.
In- dividual excitatory signal com- ponents can be isolated phar- macologically contact between a passive membrane  and a mem- brane containing voltage-gated ion channels , respec- tively, and a planar electrode.
A complete theory of neuroelectronic interfacing by semiconductor chips with embedded field-effect transis- tors is given by Fromherz .
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In principle, with slight modifications, his considerations and experimental results on the physics of the cell—insulator junction apply also for stimulation and recording with MEAs. Interpretation of the recorded signal Although the biophysical basis in principle is the same for any type of extracellular recording, the components of in- terest of the recorded voltage time series may differ.
The recorded signal may be analyzed for individual Fig. Depending on the by Buitenweg et al. A A single cell CHO cell cul- tured on a planar electrode is contacted by a patch pipette in order to control the membrane voltage in the whole-cell volt- age clamp mode. B Compari- son of intracellular and corre- sponding extracellular voltage.
A single MEA experiment can thus Here, we will emphasize the background and approaches yield data from a large number of neurons. Further in- the type and efficacy of an electrical or chemical stimulus.
BASTIEN PIANO BASICS THEORY LEVEL 2
If the activity of different neurons is in- Cardiac myocytes dependent from one another, MEA recordings will quickly compile a statistically relevant sample size and thus in- Besides the difficulty to record from contracting cells, the crease the experimental throughput [35, 45], though not electrical coupling of myocytes in the heart muscle leads the time needed to process the result.
Although conven- to special conditions for extracellular recording and the tional programs for the analysis of extracellular record- interpretation of the results.
Compared to neuronal tissue, ings provide many of the tools necessary, it should be kept the morphology and properties of the myocytes in cultures in mind that the sheer number of neurons that need to be is relatively homogeneous with respect to cell morphol- analyzed demands some sort of batch processing, requir- ogy and cell type.
Because of this, and in particular be- ing suitable adaptation of such programs . Similarly, cause of the coupling through gap junctions, the tissue even though not statistically independent, the collective within the recording horizon of an electrode can be linked response of a population of cells may yield information not to a very large cell of simple morphology, compared to available from a single neuron or the successive recording which the recording electrode is very small.
In myocyte of several neurons [41, 46, 47, 48].
The generic purpose cultures on MEAs Fig. As a result, teractions between neurons and their modulation in re- motion artifacts do not occur and the signal-to-noise ratio sponse to some stimulus [49, 50, 51, 52, 53, 54, 55, 56]. SNR is generally quite high. Depending on the overall Although these reports refer to in vivo experiments, the properties of the culture, the waveforms thus recorded analysis tools developed for this purpose are equally ap- closely match the first derivative of the transmembrane plicable to MEA recordings.
The aggregate network re- potential as shown in Fig. Since the slopes in the action sponse to a challenge by a drug, for example, in an organ- potential AP waveform reflects the currents flowing otypic brain slice, is expected to be more representative of across the membrane, the time course of the LFP relates the drugs in vivo action than studies on isolated cells. The to the transmembrane currents. Changes, though not ab- statistical analysis of such network response can be de- solute values, of some of the properties of the AP shape manding and is not yet fully established .
Together with the stability of the [57, 58, 59, 60]. This type of data usually suffers from recording configuration, the analysis of the extracellular small SNRs, so that further analysis of individual spikes field potential thus facilitates the analysis of developmen- does not extract additional information; however, it re- tal processes, arrhythmia, and drug effects on cardiac quires considerably less pre-processing of the data.
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These prop- for example, as for the electroretinogram Fig.
Quinidine and Sotalol are clinically used as anti-arrhyth- This permits the investigation of system parameters in a mica; E is an HERG channel inhibitor. Besl and Fromherz showed that this Electrical stimulation in the EC stim 1 resulted in correlated ac- model can be used to calculate the current—source density tivity in both the EC and DG, whereas stimulation in the DG stim 2 only resulted in DG activity.
Depending on the experiment, LFP lel. Such a system in principle consists of three main components: Due to local alteration of ion channel conductance, they pro- duce an extracellular field potential with a time course that is approximately equal to the transmembrane current of the active cellular compartments. The functionality and speci- ficity of the newly formed connections was shown by elec- trical stimulation and parallel recording of correlated ac- which is smaller in recordings from isolated retinas than tivity in the target tissue Fig.
As a result, teractions between neurons and their modulation in re- motion artifacts do not occur and the signal-to-noise ratio sponse to some stimulus [49, 50, 51, 52, 53, 54, 55, 56].