The aim of this work was to compare experimental investigations on effects of lidocaine, calcium and, BRL 34915 on reentries to simulated data obtained by use of a model of propagation based on the Huygens' constriction method already described in previous works. Calcium and lidocaine effects are investigated on anisotropic conduction conditions. In both cases, reduction in conduction velocities are observed. In lidocaine case, a refractory area is located along the longitudinal axis. In agreement with experimental electrical mapping, the simulations (...) show that the stabilization of reentrant excitation is mainly due to the existence of this refractory area around which the reentrant circuit can develop. The experimental study shows that BRL 34915 has both arrhythmogenic and antiarrhythmic effects. A detailed electrophysiological analysis has shown that drug infusion act on normal cardiac cells by decreasing the relative and absolute refractory period. BRL 34915 action is simulated by a decrease in the refractory period showing that the time frequency of the reentrant activity is increased and that the spatial size where the reentry is developing is becoming smaller. These two effects are arrhythmogenic, the simulated data being so in good agreement with the experimental ones. (shrink)

The present work is aimed at investigating the effects of myocardial infarction and ischemia on induction of ventricular fibrillation. Electrophysiologic effects of global and local ischemia (variation of the dispersion of refractory periods as well as conduction velocity) on initiation of reentry mechanisms was studied by means of computer simulations based on a cellular automata model of propagation of activation wave through a ventricular surface element. A local area of ischemia where effects of the dispersion of refractory periods are investigated (...) is then simulated. This is made using a Gaussian distribution characterized by its mean and standard deviation. These simulations show that ischemia is capable of initiating reentry phenomena which propagate through the whole ventricle; they are responsible for ventricular fibrillation which causes sudden cardiac death, even when ischemia only involves limited parts of the myocardium. Statistical study of the probability of reentries as a function of both of the size of ischemic zones and the rate of dispersion of refractory periods shows that the latter parameter is of primary importance in triggering cardiac reentries. (shrink)

We used computer simulations to study the possible role of the dispersion of cellular coupling, refractoriness or both, in the mechanisms underlying cardiac arrhythmias. Local ischemia was first assumed to induce cell to cell dispersion of the coupling resistance (Case 1), refractory period (Case 2), or both of them (Case 3). Our numerical experiments based on the van Capelle and Durrer model showed that vortices could not be induced by cell to cell variations. With cellular properties dispersed in a patchy (...) way within the ischemic zone, a single activation wave could give rise to abnormal activities. This demonstrates the stability of the wave front under small inhomogeneities. Probabilities of reentry, estimated for the three cases cited above showed that a severe alteration of the coupling resistance may be an important factor in the genesis of reentry. Moreover, use of isochronal maps revealed that vortices were both stable and sustained with an alteration of the coupling alone or combined with a reduction of the action potential duration. Conversely, simulations with reduction of the refractoriness alone, inducing only transient patterns, could exhibit functionally determined reentries. (shrink)

The aim of this work was to compare experimental investigations on effects of lidocaine, calcium and, BRL 34915 on reentries to simulated data obtained by use of a model of propagation based on the Huygens' constriction method already described in previous works. Calcium and lidocaine effects are investigated on anisotropic conduction conditions. In both cases, reduction in conduction velocities are observed. In lidocaine case, a refractory area is located along the longitudinal axis. In agreement with experimental electrical mapping, the simulations (...) show that the stabilization of reentrant excitation is mainly due to the existence of this refractory area around which the reentrant circuit can develop. The experimental study shows that BRL 34915 has both arrhythmogenic and antiarrhythmic effects. A detailed electrophysiological analysis has shown that drug infusion act on normal cardiac cells by decreasing the relative and absolute refractory period. BRL 34915 action is simulated by a decrease in the refractory period showing that the time frequency of the reentrant activity is increased and that the spatial size where the reentry is developing is becoming smaller. These two effects are arrhythmogenic, the simulated data being so in good agreement with the experimental ones. (shrink)

Limitations of antiarrhythmic drugs on cardiac sudden death prevention appeared since the early 80's. The "Cardiac Arrhythmia Suppression Trial"(CAST) showed more recently that mortality was significantly higher inpatients treated with some particular antiarrhythmic drugs than in non-treated patients. In this field, our group recently demonstrated that a bolus of a Class 1B antiarrhythmic drug was able to trigger a ventricular fibrillation due to transient blocks induction. The aim of the present work was to systematically study, by use of the van (...) Capelle and Durrer (VCD) model which allows to simulate ventricular activation wave propagation, the link between arrhythmogenic effects and the ability of transient blocks to possibly degenerate in severe arrhythmias. A fragment of the ventricular wall is represented by an array of 16384elements electrically coupled. Effects of induction of one or several transient blocks, as the effects of their size and duration on possible induction of reentries have been studied. Results obtained show that various combinations between these different parameters may trigger reentries, ventricular tachycardia and/or more complex patterns assimilable to ventricular fibrillation. These results clearly evidence the fact that possible induction of transient blocks may directly be related to risk factor associated to arrhythmogenic effects of antiarrhythmic drugs. (shrink)

Different approaches have been proposed in order to achieve knowledge integration for coronary care monitoring applications, usually in the form of expert systems. The clinical impact of these expert systems, which are based only on "shallow" knowledge, has not been remarkable due to the difficulties associated with the construction and maintenance of a complete knowledge base. Model-based systems represent an alternative to these problems because they allow efficient integration of the "deep" knowledge on the underlying physiological phenomena being monitored. In (...) this work, a brief review of existing model-based systems for cardiac rhythm interpretation is presented, followed by the description of a new system forCardiac Arrhythmia Recognition by Model-Based ECG Matching (CARMEM). Fundamental characteristics of CARMEM are presented; in particular, its ability to provide on-line parameter adaptation to simulate complex rhythms and to match observed ECG signals. The proposed model can be useful for the explanation of the origin of cardiac arrhythmias and contribute towards their robust characterization in the context of coronary care units. (shrink)

Ventricular Fibrillation is responsible for a majority of sudden cardiac death, but little is known about how ventricular tachycardia (VT) degenerates into ventricular fibrillation. Several clinical studies focused only on preventing VT with a class III antiarrhythmic drug resulted in many deaths. Our simulations investigate the interactions between an antiarrhythmic drug likely to suppress a VT and a Figure 8 reentry. A parameter AAR is introduced to increase the action potential duration and therefore simulate various Class III drugs. Simulations are (...) ran under several conditions (phases of the reentry, values of AAR, durations). They show that a VT can be suppressed whatever the phase of the reentry but it strongly depends on the duration of the effect. It confirms that a drug which can suppress a reentry can also worsen it. It also shows a great variety of activation patterns and thus the complexity of antiarrhythmic drugs effects. Simulations also demonstrate that suppressing VT is an increasing function of AAR. (shrink)

Much research effort has been directed in different physiological contexts towards describing realistic behaviors with differential equations. One observes obviously that more state-variables give the model more accuracy. Unfortunately, the computational cost involved is higher. A new algorithm is presented for simulating a model described by a system of differential equations in which efficiency may not be altered by its size. In order to do this, the method is based on a polynomial description of the state-variables' evolution and on a (...) computation distributed control. Evaluations and results performed with classical models like Fitzhugh Nagumo or Hodgkin Huxley, allow validation of the method and exhibits its potential to decrease the computational costs. (shrink)