[Model based study of myocardial stimulation mechanisms]. / Modellbasierte Untersuchung myokardialer Stimulationsmechanismen.

The present study investigated the mechanisms of electrical stimulation of a myocardial fibre with the aim of developing improved minimally invasive stimulation methods. Using a dynamic myocyte model, the ionic currents crossing the voltage-dependent channels of the membrane are computed. To trigger an action potential, the membrane must first be depolarized to the threshold potential, when further depolarization continues spontaneously through the avalanche-like opening of the sodium channels. For the development of an action potential, not merely the amount of charge injected into the cell during the stimulus is of importance, but an above-threshold magnitude of the stimulation current is also required. The smallest energy required is achieved when the stimulus duration is chosen to be equal to the chronaxie. A second aspect of the study concerned the far-field stimulation of a muscle fibre, achieved by generating a potential gradient along the fibre. First, using a continuous fibre model, the fibre activating function is computed. In a more detailed study, the discrete segmental structure of the fibre determined by the gap junctions is taken into account, and the impact of these junctions on the activating function analysed. By optimizing the electrode configuration, an appropriate activating function results which guarantees successful stimulation when its maximum is above than threshold potential. The most important finding is that the myocardium can be stimulated by floating electrodes, thus opening up new possibilities for a less invasive electro-stimulation of the heart.

[Simulation of myocardial action potentials of various cell types in relation to neural parameters]. / Simulation myokardialer Aktionspotentiale verschiedener Zelltypen in Abhängigkeit von nervalen Einflussfaktoren.

Action potentials of various myocardial cell types were simulated in a computer model based on current knowledge of the electrical properties of ionic channels and pumps in the ventricular cell membrane and the sarcoplasmic reticulum. The transport mechanisms of sodium, potassium, calcium and chlorine ions through the cell membrane are described mathematically, as is the exchange of calcium between the myoplasm and sarcoplasmic reticulum. Ten ionic channels and three pumps of the cell membrane are taken into account, while three channels and one pump of the sarcoplasmic reticulum are considered in the computations. For the first time, the transient outward potassium current IK,to was simulated, the effect of which on the early repolarisation phase of the action potential was reproducible in the model. Calcium buffers in the myoplasm and the sarcoplasmic reticulum are also considered. From the resulting ionic currents through the channels and pumps, the membrane potential is computed using an equivalent circuit diagram of the cell membrane. In particular the influence of neural activity on channel conductance and the probability of channel patency were taken into account. By means of this model, different shapes of ventricular action potentials were simulated. The action potentials of epicardial cells, M-cells, endocardial cells and Purkinje fibres were accurately simulated. In addition, the effects of sympathetic drive and various drugs were demonstrated in the model as well as the shortening of the action potential duration with increasing stimulation frequency.

[Measuring intracardiac impedance for the determination of sympathetic nerve activity in frequency-adapted electrostimulation--Part 2: Clinical results]. / Intrakardiale Impedanzmessung zur Bestimmung der Sympathikusaktivität bei frequenzadaptiver Elektrostimulation--Teil 2: Klinische Ergebnisse.

The results of a multicenter clinical study involving patients receiving the first ANS controlled rate adaptive pacemaker are presented. In the patients with primary or secondary chronotropic insufficiency, it is possible to reestablish the closed loop control system that includes the baroreceptors, the medulla oblongata, the cardiac output and the mean arterial blood pressure. This system serves to keep the blood pressure constant in the face of changing demands on the circulation. Utilizing intracardiac impedance measurements, the myocardial contractility can be determined, which contains information about the current sympathetic tone, and thus represents an excellent physiological input for a rate adaptive mechanism. The results presented are taken from a study population of over 200 patients. The objective evaluation of this new approach was performed echocardiographically, by ergometry and 24-hour Holter monitoring.

[Measuring intracardiac impedance for determining sympathetic nerve activity in frequency-adjustment electrostimulation--1: Biomedical technical principles]. / Intrakardiale Impedanzmessung zur Bestimmung der Sympathikusaktivität bei frequenzadaptiver Elektrostimulation--Teil 1: Biomedizintechnische Grundlagen.

Modern Pacemaker technology makes it possible to adapt the pacing rate to hemodynamic requirements. The most ambitious approach aims at restoring the physiological closed-loop system by utilizing the information supplied by the Autonomic Nervous System and extracted from myocardial contractile performance. Measurement is accomplished by the impedance method using the stimulating electrode as the measuring electrode. The Ventricular Inotropic Parameter (VIP) has been identified as an ANS-dependent parameter. A special detection algorithm, the Regional Effective Slope Quantity (RQ), with a high ANS sensitivity has been developed specially for the purpose. Rate adaptation is achieved by using an individually-adjustable Inotropic Index (II). The concept has been evaluated in a multicenter study employing a standardized exercise protocol. The clinical results will be presented in Part 2 of this paper.